1

TABLETSPRESENTED BY

ARANTHAJJOSEPHFIRST YEAR MPHARM

PHARMACEUTICS St josephs college of pharmacy cherthala

2 CONTENTS

Introduction Formulation Design Manufacturing

3 TABLETS

Tablets are solid preparations Consisting of one or more active ingredient Obtained by compressing uniform volumes of particles into various size and shape

4 THE ADVANTAGES OF THE TABLET bull They are unit dosage

bull Greatest dose precision and the least content variability

bull Cost is lowest of all oral dosage form

bull Lighter and compact

bull Easiest and cheapest to package

bull Easy to swallowing

bull Special release product is possible by enteric coating or delayed release product

5

bull odour and bitter taste can be masked by coating technique

bull Suitable for large scale production

bull Greatest chemical mechanical and microbial stability over all oral dosage form

bull Product identification is easy and cheapest

6DISADVANTAGES OF TABLET

bull Difficult to swallow in case of children and unconscious patients

bull Some drugs resist compression into dense compacts

bull Drugs with poor wetting slow dissolution properties is difficult to formulate

bull Bitter testing drugs drugs with an objectionable odor or drugs that are sensitive to oxygen may require encapsulation or coating

7DIFFERENT TYPES OF TABLETS

(A) Tablets ingested orally 1 Compressed tablet eg Paracetamol

tablet 2 Multiple compressed tablet bull layered tablet bull Compression coated tablets

4 Delayed release tablet eg Enteric coated Bisacodyl

5 Sugar coated tablet eg Multivitamin tablet

6 Film coated tablet eg Metronidazole tablet

7 Chewable tablet eg Antacid tablet

8 Tablets used in oral cavity 1 Buccal tablet eg Vitamin-c tablet 2 Sublingual tablet eg Vicks Menthol

tablet 3 Troches or lozenges 4 Dental cone

9 (c) Tablets administered by other route 1 Implantation tablet 2 Vaginal tablet eg Clotrimazole tablet

(D) Tablets used to prepare solution

1 Effervescent tablet eg Dispirin tablet (Aspirin)

2 Dispensing tablet eg Enzyme tablet (Digiplex) 3 Hypodermic tablet

4 Tablet triturates eg Enzyme tablet (Digiplex)

10 TABLET GRANULATION

Granulation The process in which the primary powders particles are made adhere to form larger Multi particle entities called granulation

1

11Powders intended for compression into tablets

must possess two essential properties

Powder fluidity or flowabilitybull Powder flow can be improved mechanically by the

use of vibrators glidantPowder compressibilitybull The property of forming a stable intact

compact mass when pressure is applied is called powder compressibility

12ADVANTAGES OF GRANNULATION

bull To avoid powder segregation

bull To enhance the flow of powder

bull To produce uniform mixtures

bull To produce dust free formulations

bull To eliminate poor content uniformity

bull To improve compaction characteristics

of mix

13 Manufacturing of granules

Dry granulation method wet granulation method

Direct compression compression granulation Wet granulation

14Dry granulation

Compaction of powder

milling

screening

15 AdvantagesLess

equipments amp space

Eliminate need of binder

solution

Disadvantages

No uniform

color distributio

n

Process create

more dust

16Direct compression

Some Crystalline substances can compress directly Directly compressible diluent is an

Inert Compactable Maintain compression capacity even after adding disintegrates

and other ingredients Direct compression materials should posses

Good flow and compressibility Inert Tasteless Reworkable Inexpensive Able to disintegrate

17

DrugExcipientsDiluentsDisintegrantLarge sized tabletsSlugsGranulesDisintegrantGlidant

LubricanttabletsCompression granulation

Weighing

Mixing [blender]

Slugging[tablet press roller compactorScreening sieve[20-25]

Mixing

Compression [tablet press]

18

Important Steps1 Milling of drugs and excipients2 Mixing of ingredients3 Tablet compression

19 COMPRESSION GRANNULATION Dose of a drug is too high for its

compression Drug sensitive to heat and moisture Aspirin multi vitamins Compaction of components of tablets by

means of tablet press or machine Milling and screening prior to fluid

compression

20 Roller compactor

On a large scale compression granulation can also be performed on a roller compactor

Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch

21

It requires drugs or excipients with cohesive properties

Large particles must be used rarr (acceptable flowability and bulk density)

If the drug powder has low compatability it is difficult to form into tablets

Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose

LIMITATIONS OF DRY GRANULATION

22 WET GRANULATION

It involves massing of a mix of dry Primary powder particles using a Granulating fluid

The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol

The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying

23

bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening

24 Advantages of wet granulation

prevent segregation of the constituents of the powder blend

Improved cohesiveness and compressibility

To improve homogeneity Uniform distribution of contents and

colour The dissolution rate of hydrophobic

drugs may be improved by wet granulation method

25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive

drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to

migration of dyes during drying stage

EquipmentsTraditionally dry mixing in wet granulation

process has been carried out usingSigma blade mixerHeavy-duty planetary mixer

26Granulation mechanism To form grannulesbond must be formed

between powder particles So they adhere Bond should be strong to prevent break

down 5 bonding mechanism

Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild

particles Formation of solid bridges after

solvent evaporation

27 Mechanism of granule formation

Divided into 3 Nucleation Transition Ball growth

28 GRANULATION EQUIPMENTS

Single pot granulator

High shear mixture granulator

Fluid bed granulator

29

Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment

eg Single Pot Processor One-Pot Processor

30 Single pot granulator

31 Rapid mixer granulator

32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)

Liquid binder addition (Approx 1-2 mins)

Wet massing

Wet sieving of granules

Drying

Dry sieving of granules

33

Short processing time

Lesser amount of liquid binders required

Highly cohesive material can be granulated

Increase in temperature may cause chemical degradation of thermolabile material

Over wetting of granules can lead to

large size lumps formation

ADVANTAGES DISADVANTAGES

34 Fluid bed granulator

Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas

Granulating and drying can be completed in one

step inside the machine

35

-Homogeneous granules

---Gentle product handling

--Uniform spraying of all particles in the fluid bed

36 Advantages Reduces dust formation during

processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor

space requirements

DISADVANTAGES

The Fluid Bed cleaning is labor-intensive and time consuming

Difficulty of assuring reproducibility

37

Tablets Excipients

38

The common types of tabletrsquos excipients are described in the figure

Diluents

Binders $ adhesives

Disintegrants

Colours sweeten

ers $ flavors

39Diluent or filler Bulking agent

Increase size of the tablet Suitable for handling

Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate

40 Requirements for a good diluent

Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

2 CONTENTS

Introduction Formulation Design Manufacturing

3 TABLETS

Tablets are solid preparations Consisting of one or more active ingredient Obtained by compressing uniform volumes of particles into various size and shape

4 THE ADVANTAGES OF THE TABLET bull They are unit dosage

bull Greatest dose precision and the least content variability

bull Cost is lowest of all oral dosage form

bull Lighter and compact

bull Easiest and cheapest to package

bull Easy to swallowing

bull Special release product is possible by enteric coating or delayed release product

5

bull odour and bitter taste can be masked by coating technique

bull Suitable for large scale production

bull Greatest chemical mechanical and microbial stability over all oral dosage form

bull Product identification is easy and cheapest

6DISADVANTAGES OF TABLET

bull Difficult to swallow in case of children and unconscious patients

bull Some drugs resist compression into dense compacts

bull Drugs with poor wetting slow dissolution properties is difficult to formulate

bull Bitter testing drugs drugs with an objectionable odor or drugs that are sensitive to oxygen may require encapsulation or coating

7DIFFERENT TYPES OF TABLETS

(A) Tablets ingested orally 1 Compressed tablet eg Paracetamol

tablet 2 Multiple compressed tablet bull layered tablet bull Compression coated tablets

4 Delayed release tablet eg Enteric coated Bisacodyl

5 Sugar coated tablet eg Multivitamin tablet

6 Film coated tablet eg Metronidazole tablet

7 Chewable tablet eg Antacid tablet

8 Tablets used in oral cavity 1 Buccal tablet eg Vitamin-c tablet 2 Sublingual tablet eg Vicks Menthol

tablet 3 Troches or lozenges 4 Dental cone

9 (c) Tablets administered by other route 1 Implantation tablet 2 Vaginal tablet eg Clotrimazole tablet

(D) Tablets used to prepare solution

1 Effervescent tablet eg Dispirin tablet (Aspirin)

2 Dispensing tablet eg Enzyme tablet (Digiplex) 3 Hypodermic tablet

4 Tablet triturates eg Enzyme tablet (Digiplex)

10 TABLET GRANULATION

Granulation The process in which the primary powders particles are made adhere to form larger Multi particle entities called granulation

1

11Powders intended for compression into tablets

must possess two essential properties

Powder fluidity or flowabilitybull Powder flow can be improved mechanically by the

use of vibrators glidantPowder compressibilitybull The property of forming a stable intact

compact mass when pressure is applied is called powder compressibility

12ADVANTAGES OF GRANNULATION

bull To avoid powder segregation

bull To enhance the flow of powder

bull To produce uniform mixtures

bull To produce dust free formulations

bull To eliminate poor content uniformity

bull To improve compaction characteristics

of mix

13 Manufacturing of granules

Dry granulation method wet granulation method

Direct compression compression granulation Wet granulation

14Dry granulation

Compaction of powder

milling

screening

15 AdvantagesLess

equipments amp space

Eliminate need of binder

solution

Disadvantages

No uniform

color distributio

n

Process create

more dust

16Direct compression

Some Crystalline substances can compress directly Directly compressible diluent is an

Inert Compactable Maintain compression capacity even after adding disintegrates

and other ingredients Direct compression materials should posses

Good flow and compressibility Inert Tasteless Reworkable Inexpensive Able to disintegrate

17

DrugExcipientsDiluentsDisintegrantLarge sized tabletsSlugsGranulesDisintegrantGlidant

LubricanttabletsCompression granulation

Weighing

Mixing [blender]

Slugging[tablet press roller compactorScreening sieve[20-25]

Mixing

Compression [tablet press]

18

Important Steps1 Milling of drugs and excipients2 Mixing of ingredients3 Tablet compression

19 COMPRESSION GRANNULATION Dose of a drug is too high for its

compression Drug sensitive to heat and moisture Aspirin multi vitamins Compaction of components of tablets by

means of tablet press or machine Milling and screening prior to fluid

compression

20 Roller compactor

On a large scale compression granulation can also be performed on a roller compactor

Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch

21

It requires drugs or excipients with cohesive properties

Large particles must be used rarr (acceptable flowability and bulk density)

If the drug powder has low compatability it is difficult to form into tablets

Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose

LIMITATIONS OF DRY GRANULATION

22 WET GRANULATION

It involves massing of a mix of dry Primary powder particles using a Granulating fluid

The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol

The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying

23

bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening

24 Advantages of wet granulation

prevent segregation of the constituents of the powder blend

Improved cohesiveness and compressibility

To improve homogeneity Uniform distribution of contents and

colour The dissolution rate of hydrophobic

drugs may be improved by wet granulation method

25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive

drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to

migration of dyes during drying stage

EquipmentsTraditionally dry mixing in wet granulation

process has been carried out usingSigma blade mixerHeavy-duty planetary mixer

26Granulation mechanism To form grannulesbond must be formed

between powder particles So they adhere Bond should be strong to prevent break

down 5 bonding mechanism

Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild

particles Formation of solid bridges after

solvent evaporation

27 Mechanism of granule formation

Divided into 3 Nucleation Transition Ball growth

28 GRANULATION EQUIPMENTS

Single pot granulator

High shear mixture granulator

Fluid bed granulator

29

Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment

eg Single Pot Processor One-Pot Processor

30 Single pot granulator

31 Rapid mixer granulator

32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)

Liquid binder addition (Approx 1-2 mins)

Wet massing

Wet sieving of granules

Drying

Dry sieving of granules

33

Short processing time

Lesser amount of liquid binders required

Highly cohesive material can be granulated

Increase in temperature may cause chemical degradation of thermolabile material

Over wetting of granules can lead to

large size lumps formation

ADVANTAGES DISADVANTAGES

34 Fluid bed granulator

Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas

Granulating and drying can be completed in one

step inside the machine

35

-Homogeneous granules

---Gentle product handling

--Uniform spraying of all particles in the fluid bed

36 Advantages Reduces dust formation during

processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor

space requirements

DISADVANTAGES

The Fluid Bed cleaning is labor-intensive and time consuming

Difficulty of assuring reproducibility

37

Tablets Excipients

38

The common types of tabletrsquos excipients are described in the figure

Diluents

Binders $ adhesives

Disintegrants

Colours sweeten

ers $ flavors

39Diluent or filler Bulking agent

Increase size of the tablet Suitable for handling

Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate

40 Requirements for a good diluent

Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

3 TABLETS

Tablets are solid preparations Consisting of one or more active ingredient Obtained by compressing uniform volumes of particles into various size and shape

4 THE ADVANTAGES OF THE TABLET bull They are unit dosage

bull Greatest dose precision and the least content variability

bull Cost is lowest of all oral dosage form

bull Lighter and compact

bull Easiest and cheapest to package

bull Easy to swallowing

bull Special release product is possible by enteric coating or delayed release product

5

bull odour and bitter taste can be masked by coating technique

bull Suitable for large scale production

bull Greatest chemical mechanical and microbial stability over all oral dosage form

bull Product identification is easy and cheapest

6DISADVANTAGES OF TABLET

bull Difficult to swallow in case of children and unconscious patients

bull Some drugs resist compression into dense compacts

bull Drugs with poor wetting slow dissolution properties is difficult to formulate

bull Bitter testing drugs drugs with an objectionable odor or drugs that are sensitive to oxygen may require encapsulation or coating

7DIFFERENT TYPES OF TABLETS

(A) Tablets ingested orally 1 Compressed tablet eg Paracetamol

tablet 2 Multiple compressed tablet bull layered tablet bull Compression coated tablets

4 Delayed release tablet eg Enteric coated Bisacodyl

5 Sugar coated tablet eg Multivitamin tablet

6 Film coated tablet eg Metronidazole tablet

7 Chewable tablet eg Antacid tablet

8 Tablets used in oral cavity 1 Buccal tablet eg Vitamin-c tablet 2 Sublingual tablet eg Vicks Menthol

tablet 3 Troches or lozenges 4 Dental cone

9 (c) Tablets administered by other route 1 Implantation tablet 2 Vaginal tablet eg Clotrimazole tablet

(D) Tablets used to prepare solution

1 Effervescent tablet eg Dispirin tablet (Aspirin)

2 Dispensing tablet eg Enzyme tablet (Digiplex) 3 Hypodermic tablet

4 Tablet triturates eg Enzyme tablet (Digiplex)

10 TABLET GRANULATION

Granulation The process in which the primary powders particles are made adhere to form larger Multi particle entities called granulation

1

11Powders intended for compression into tablets

must possess two essential properties

Powder fluidity or flowabilitybull Powder flow can be improved mechanically by the

use of vibrators glidantPowder compressibilitybull The property of forming a stable intact

compact mass when pressure is applied is called powder compressibility

12ADVANTAGES OF GRANNULATION

bull To avoid powder segregation

bull To enhance the flow of powder

bull To produce uniform mixtures

bull To produce dust free formulations

bull To eliminate poor content uniformity

bull To improve compaction characteristics

of mix

13 Manufacturing of granules

Dry granulation method wet granulation method

Direct compression compression granulation Wet granulation

14Dry granulation

Compaction of powder

milling

screening

15 AdvantagesLess

equipments amp space

Eliminate need of binder

solution

Disadvantages

No uniform

color distributio

n

Process create

more dust

16Direct compression

Some Crystalline substances can compress directly Directly compressible diluent is an

Inert Compactable Maintain compression capacity even after adding disintegrates

and other ingredients Direct compression materials should posses

Good flow and compressibility Inert Tasteless Reworkable Inexpensive Able to disintegrate

17

DrugExcipientsDiluentsDisintegrantLarge sized tabletsSlugsGranulesDisintegrantGlidant

LubricanttabletsCompression granulation

Weighing

Mixing [blender]

Slugging[tablet press roller compactorScreening sieve[20-25]

Mixing

Compression [tablet press]

18

Important Steps1 Milling of drugs and excipients2 Mixing of ingredients3 Tablet compression

19 COMPRESSION GRANNULATION Dose of a drug is too high for its

compression Drug sensitive to heat and moisture Aspirin multi vitamins Compaction of components of tablets by

means of tablet press or machine Milling and screening prior to fluid

compression

20 Roller compactor

On a large scale compression granulation can also be performed on a roller compactor

Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch

21

It requires drugs or excipients with cohesive properties

Large particles must be used rarr (acceptable flowability and bulk density)

If the drug powder has low compatability it is difficult to form into tablets

Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose

LIMITATIONS OF DRY GRANULATION

22 WET GRANULATION

It involves massing of a mix of dry Primary powder particles using a Granulating fluid

The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol

The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying

23

bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening

24 Advantages of wet granulation

prevent segregation of the constituents of the powder blend

Improved cohesiveness and compressibility

To improve homogeneity Uniform distribution of contents and

colour The dissolution rate of hydrophobic

drugs may be improved by wet granulation method

25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive

drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to

migration of dyes during drying stage

EquipmentsTraditionally dry mixing in wet granulation

process has been carried out usingSigma blade mixerHeavy-duty planetary mixer

26Granulation mechanism To form grannulesbond must be formed

between powder particles So they adhere Bond should be strong to prevent break

down 5 bonding mechanism

Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild

particles Formation of solid bridges after

solvent evaporation

27 Mechanism of granule formation

Divided into 3 Nucleation Transition Ball growth

28 GRANULATION EQUIPMENTS

Single pot granulator

High shear mixture granulator

Fluid bed granulator

29

Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment

eg Single Pot Processor One-Pot Processor

30 Single pot granulator

31 Rapid mixer granulator

32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)

Liquid binder addition (Approx 1-2 mins)

Wet massing

Wet sieving of granules

Drying

Dry sieving of granules

33

Short processing time

Lesser amount of liquid binders required

Highly cohesive material can be granulated

Increase in temperature may cause chemical degradation of thermolabile material

Over wetting of granules can lead to

large size lumps formation

ADVANTAGES DISADVANTAGES

34 Fluid bed granulator

Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas

Granulating and drying can be completed in one

step inside the machine

35

-Homogeneous granules

---Gentle product handling

--Uniform spraying of all particles in the fluid bed

36 Advantages Reduces dust formation during

processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor

space requirements

DISADVANTAGES

The Fluid Bed cleaning is labor-intensive and time consuming

Difficulty of assuring reproducibility

37

Tablets Excipients

38

The common types of tabletrsquos excipients are described in the figure

Diluents

Binders $ adhesives

Disintegrants

Colours sweeten

ers $ flavors

39Diluent or filler Bulking agent

Increase size of the tablet Suitable for handling

Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate

40 Requirements for a good diluent

Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

4 THE ADVANTAGES OF THE TABLET bull They are unit dosage

bull Greatest dose precision and the least content variability

bull Cost is lowest of all oral dosage form

bull Lighter and compact

bull Easiest and cheapest to package

bull Easy to swallowing

bull Special release product is possible by enteric coating or delayed release product

5

bull odour and bitter taste can be masked by coating technique

bull Suitable for large scale production

bull Greatest chemical mechanical and microbial stability over all oral dosage form

bull Product identification is easy and cheapest

6DISADVANTAGES OF TABLET

bull Difficult to swallow in case of children and unconscious patients

bull Some drugs resist compression into dense compacts

bull Drugs with poor wetting slow dissolution properties is difficult to formulate

bull Bitter testing drugs drugs with an objectionable odor or drugs that are sensitive to oxygen may require encapsulation or coating

7DIFFERENT TYPES OF TABLETS

(A) Tablets ingested orally 1 Compressed tablet eg Paracetamol

tablet 2 Multiple compressed tablet bull layered tablet bull Compression coated tablets

4 Delayed release tablet eg Enteric coated Bisacodyl

5 Sugar coated tablet eg Multivitamin tablet

6 Film coated tablet eg Metronidazole tablet

7 Chewable tablet eg Antacid tablet

8 Tablets used in oral cavity 1 Buccal tablet eg Vitamin-c tablet 2 Sublingual tablet eg Vicks Menthol

tablet 3 Troches or lozenges 4 Dental cone

9 (c) Tablets administered by other route 1 Implantation tablet 2 Vaginal tablet eg Clotrimazole tablet

(D) Tablets used to prepare solution

1 Effervescent tablet eg Dispirin tablet (Aspirin)

2 Dispensing tablet eg Enzyme tablet (Digiplex) 3 Hypodermic tablet

4 Tablet triturates eg Enzyme tablet (Digiplex)

10 TABLET GRANULATION

Granulation The process in which the primary powders particles are made adhere to form larger Multi particle entities called granulation

1

11Powders intended for compression into tablets

must possess two essential properties

Powder fluidity or flowabilitybull Powder flow can be improved mechanically by the

use of vibrators glidantPowder compressibilitybull The property of forming a stable intact

compact mass when pressure is applied is called powder compressibility

12ADVANTAGES OF GRANNULATION

bull To avoid powder segregation

bull To enhance the flow of powder

bull To produce uniform mixtures

bull To produce dust free formulations

bull To eliminate poor content uniformity

bull To improve compaction characteristics

of mix

13 Manufacturing of granules

Dry granulation method wet granulation method

Direct compression compression granulation Wet granulation

14Dry granulation

Compaction of powder

milling

screening

15 AdvantagesLess

equipments amp space

Eliminate need of binder

solution

Disadvantages

No uniform

color distributio

n

Process create

more dust

16Direct compression

Some Crystalline substances can compress directly Directly compressible diluent is an

Inert Compactable Maintain compression capacity even after adding disintegrates

and other ingredients Direct compression materials should posses

Good flow and compressibility Inert Tasteless Reworkable Inexpensive Able to disintegrate

17

DrugExcipientsDiluentsDisintegrantLarge sized tabletsSlugsGranulesDisintegrantGlidant

LubricanttabletsCompression granulation

Weighing

Mixing [blender]

Slugging[tablet press roller compactorScreening sieve[20-25]

Mixing

Compression [tablet press]

18

Important Steps1 Milling of drugs and excipients2 Mixing of ingredients3 Tablet compression

19 COMPRESSION GRANNULATION Dose of a drug is too high for its

compression Drug sensitive to heat and moisture Aspirin multi vitamins Compaction of components of tablets by

means of tablet press or machine Milling and screening prior to fluid

compression

20 Roller compactor

On a large scale compression granulation can also be performed on a roller compactor

Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch

21

It requires drugs or excipients with cohesive properties

Large particles must be used rarr (acceptable flowability and bulk density)

If the drug powder has low compatability it is difficult to form into tablets

Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose

LIMITATIONS OF DRY GRANULATION

22 WET GRANULATION

It involves massing of a mix of dry Primary powder particles using a Granulating fluid

The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol

The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying

23

bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening

24 Advantages of wet granulation

prevent segregation of the constituents of the powder blend

Improved cohesiveness and compressibility

To improve homogeneity Uniform distribution of contents and

colour The dissolution rate of hydrophobic

drugs may be improved by wet granulation method

25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive

drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to

migration of dyes during drying stage

EquipmentsTraditionally dry mixing in wet granulation

process has been carried out usingSigma blade mixerHeavy-duty planetary mixer

26Granulation mechanism To form grannulesbond must be formed

between powder particles So they adhere Bond should be strong to prevent break

down 5 bonding mechanism

Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild

particles Formation of solid bridges after

solvent evaporation

27 Mechanism of granule formation

Divided into 3 Nucleation Transition Ball growth

28 GRANULATION EQUIPMENTS

Single pot granulator

High shear mixture granulator

Fluid bed granulator

29

Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment

eg Single Pot Processor One-Pot Processor

30 Single pot granulator

31 Rapid mixer granulator

32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)

Liquid binder addition (Approx 1-2 mins)

Wet massing

Wet sieving of granules

Drying

Dry sieving of granules

33

Short processing time

Lesser amount of liquid binders required

Highly cohesive material can be granulated

Increase in temperature may cause chemical degradation of thermolabile material

Over wetting of granules can lead to

large size lumps formation

ADVANTAGES DISADVANTAGES

34 Fluid bed granulator

Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas

Granulating and drying can be completed in one

step inside the machine

35

-Homogeneous granules

---Gentle product handling

--Uniform spraying of all particles in the fluid bed

36 Advantages Reduces dust formation during

processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor

space requirements

DISADVANTAGES

The Fluid Bed cleaning is labor-intensive and time consuming

Difficulty of assuring reproducibility

37

Tablets Excipients

38

The common types of tabletrsquos excipients are described in the figure

Diluents

Binders $ adhesives

Disintegrants

Colours sweeten

ers $ flavors

39Diluent or filler Bulking agent

Increase size of the tablet Suitable for handling

Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate

40 Requirements for a good diluent

Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

5

bull odour and bitter taste can be masked by coating technique

bull Suitable for large scale production

bull Greatest chemical mechanical and microbial stability over all oral dosage form

bull Product identification is easy and cheapest

6DISADVANTAGES OF TABLET

bull Difficult to swallow in case of children and unconscious patients

bull Some drugs resist compression into dense compacts

bull Drugs with poor wetting slow dissolution properties is difficult to formulate

bull Bitter testing drugs drugs with an objectionable odor or drugs that are sensitive to oxygen may require encapsulation or coating

7DIFFERENT TYPES OF TABLETS

(A) Tablets ingested orally 1 Compressed tablet eg Paracetamol

tablet 2 Multiple compressed tablet bull layered tablet bull Compression coated tablets

4 Delayed release tablet eg Enteric coated Bisacodyl

5 Sugar coated tablet eg Multivitamin tablet

6 Film coated tablet eg Metronidazole tablet

7 Chewable tablet eg Antacid tablet

8 Tablets used in oral cavity 1 Buccal tablet eg Vitamin-c tablet 2 Sublingual tablet eg Vicks Menthol

tablet 3 Troches or lozenges 4 Dental cone

9 (c) Tablets administered by other route 1 Implantation tablet 2 Vaginal tablet eg Clotrimazole tablet

(D) Tablets used to prepare solution

1 Effervescent tablet eg Dispirin tablet (Aspirin)

2 Dispensing tablet eg Enzyme tablet (Digiplex) 3 Hypodermic tablet

4 Tablet triturates eg Enzyme tablet (Digiplex)

10 TABLET GRANULATION

Granulation The process in which the primary powders particles are made adhere to form larger Multi particle entities called granulation

1

11Powders intended for compression into tablets

must possess two essential properties

Powder fluidity or flowabilitybull Powder flow can be improved mechanically by the

use of vibrators glidantPowder compressibilitybull The property of forming a stable intact

compact mass when pressure is applied is called powder compressibility

12ADVANTAGES OF GRANNULATION

bull To avoid powder segregation

bull To enhance the flow of powder

bull To produce uniform mixtures

bull To produce dust free formulations

bull To eliminate poor content uniformity

bull To improve compaction characteristics

of mix

13 Manufacturing of granules

Dry granulation method wet granulation method

Direct compression compression granulation Wet granulation

14Dry granulation

Compaction of powder

milling

screening

15 AdvantagesLess

equipments amp space

Eliminate need of binder

solution

Disadvantages

No uniform

color distributio

n

Process create

more dust

16Direct compression

Some Crystalline substances can compress directly Directly compressible diluent is an

Inert Compactable Maintain compression capacity even after adding disintegrates

and other ingredients Direct compression materials should posses

Good flow and compressibility Inert Tasteless Reworkable Inexpensive Able to disintegrate

17

DrugExcipientsDiluentsDisintegrantLarge sized tabletsSlugsGranulesDisintegrantGlidant

LubricanttabletsCompression granulation

Weighing

Mixing [blender]

Slugging[tablet press roller compactorScreening sieve[20-25]

Mixing

Compression [tablet press]

18

Important Steps1 Milling of drugs and excipients2 Mixing of ingredients3 Tablet compression

19 COMPRESSION GRANNULATION Dose of a drug is too high for its

compression Drug sensitive to heat and moisture Aspirin multi vitamins Compaction of components of tablets by

means of tablet press or machine Milling and screening prior to fluid

compression

20 Roller compactor

On a large scale compression granulation can also be performed on a roller compactor

Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch

21

It requires drugs or excipients with cohesive properties

Large particles must be used rarr (acceptable flowability and bulk density)

If the drug powder has low compatability it is difficult to form into tablets

Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose

LIMITATIONS OF DRY GRANULATION

22 WET GRANULATION

It involves massing of a mix of dry Primary powder particles using a Granulating fluid

The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol

The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying

23

bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening

24 Advantages of wet granulation

prevent segregation of the constituents of the powder blend

Improved cohesiveness and compressibility

To improve homogeneity Uniform distribution of contents and

colour The dissolution rate of hydrophobic

drugs may be improved by wet granulation method

25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive

drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to

migration of dyes during drying stage

EquipmentsTraditionally dry mixing in wet granulation

process has been carried out usingSigma blade mixerHeavy-duty planetary mixer

26Granulation mechanism To form grannulesbond must be formed

between powder particles So they adhere Bond should be strong to prevent break

down 5 bonding mechanism

Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild

particles Formation of solid bridges after

solvent evaporation

27 Mechanism of granule formation

Divided into 3 Nucleation Transition Ball growth

28 GRANULATION EQUIPMENTS

Single pot granulator

High shear mixture granulator

Fluid bed granulator

29

Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment

eg Single Pot Processor One-Pot Processor

30 Single pot granulator

31 Rapid mixer granulator

32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)

Liquid binder addition (Approx 1-2 mins)

Wet massing

Wet sieving of granules

Drying

Dry sieving of granules

33

Short processing time

Lesser amount of liquid binders required

Highly cohesive material can be granulated

Increase in temperature may cause chemical degradation of thermolabile material

Over wetting of granules can lead to

large size lumps formation

ADVANTAGES DISADVANTAGES

34 Fluid bed granulator

Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas

Granulating and drying can be completed in one

step inside the machine

35

-Homogeneous granules

---Gentle product handling

--Uniform spraying of all particles in the fluid bed

36 Advantages Reduces dust formation during

processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor

space requirements

DISADVANTAGES

The Fluid Bed cleaning is labor-intensive and time consuming

Difficulty of assuring reproducibility

37

Tablets Excipients

38

The common types of tabletrsquos excipients are described in the figure

Diluents

Binders $ adhesives

Disintegrants

Colours sweeten

ers $ flavors

39Diluent or filler Bulking agent

Increase size of the tablet Suitable for handling

Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate

40 Requirements for a good diluent

Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

6DISADVANTAGES OF TABLET

bull Difficult to swallow in case of children and unconscious patients

bull Some drugs resist compression into dense compacts

bull Drugs with poor wetting slow dissolution properties is difficult to formulate

bull Bitter testing drugs drugs with an objectionable odor or drugs that are sensitive to oxygen may require encapsulation or coating

7DIFFERENT TYPES OF TABLETS

(A) Tablets ingested orally 1 Compressed tablet eg Paracetamol

tablet 2 Multiple compressed tablet bull layered tablet bull Compression coated tablets

4 Delayed release tablet eg Enteric coated Bisacodyl

5 Sugar coated tablet eg Multivitamin tablet

6 Film coated tablet eg Metronidazole tablet

7 Chewable tablet eg Antacid tablet

8 Tablets used in oral cavity 1 Buccal tablet eg Vitamin-c tablet 2 Sublingual tablet eg Vicks Menthol

tablet 3 Troches or lozenges 4 Dental cone

9 (c) Tablets administered by other route 1 Implantation tablet 2 Vaginal tablet eg Clotrimazole tablet

(D) Tablets used to prepare solution

1 Effervescent tablet eg Dispirin tablet (Aspirin)

2 Dispensing tablet eg Enzyme tablet (Digiplex) 3 Hypodermic tablet

4 Tablet triturates eg Enzyme tablet (Digiplex)

10 TABLET GRANULATION

Granulation The process in which the primary powders particles are made adhere to form larger Multi particle entities called granulation

1

11Powders intended for compression into tablets

must possess two essential properties

Powder fluidity or flowabilitybull Powder flow can be improved mechanically by the

use of vibrators glidantPowder compressibilitybull The property of forming a stable intact

compact mass when pressure is applied is called powder compressibility

12ADVANTAGES OF GRANNULATION

bull To avoid powder segregation

bull To enhance the flow of powder

bull To produce uniform mixtures

bull To produce dust free formulations

bull To eliminate poor content uniformity

bull To improve compaction characteristics

of mix

13 Manufacturing of granules

Dry granulation method wet granulation method

Direct compression compression granulation Wet granulation

14Dry granulation

Compaction of powder

milling

screening

15 AdvantagesLess

equipments amp space

Eliminate need of binder

solution

Disadvantages

No uniform

color distributio

n

Process create

more dust

16Direct compression

Some Crystalline substances can compress directly Directly compressible diluent is an

Inert Compactable Maintain compression capacity even after adding disintegrates

and other ingredients Direct compression materials should posses

Good flow and compressibility Inert Tasteless Reworkable Inexpensive Able to disintegrate

17

DrugExcipientsDiluentsDisintegrantLarge sized tabletsSlugsGranulesDisintegrantGlidant

LubricanttabletsCompression granulation

Weighing

Mixing [blender]

Slugging[tablet press roller compactorScreening sieve[20-25]

Mixing

Compression [tablet press]

18

Important Steps1 Milling of drugs and excipients2 Mixing of ingredients3 Tablet compression

19 COMPRESSION GRANNULATION Dose of a drug is too high for its

compression Drug sensitive to heat and moisture Aspirin multi vitamins Compaction of components of tablets by

means of tablet press or machine Milling and screening prior to fluid

compression

20 Roller compactor

On a large scale compression granulation can also be performed on a roller compactor

Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch

21

It requires drugs or excipients with cohesive properties

Large particles must be used rarr (acceptable flowability and bulk density)

If the drug powder has low compatability it is difficult to form into tablets

Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose

LIMITATIONS OF DRY GRANULATION

22 WET GRANULATION

It involves massing of a mix of dry Primary powder particles using a Granulating fluid

The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol

The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying

23

bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening

24 Advantages of wet granulation

prevent segregation of the constituents of the powder blend

Improved cohesiveness and compressibility

To improve homogeneity Uniform distribution of contents and

colour The dissolution rate of hydrophobic

drugs may be improved by wet granulation method

25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive

drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to

migration of dyes during drying stage

EquipmentsTraditionally dry mixing in wet granulation

process has been carried out usingSigma blade mixerHeavy-duty planetary mixer

26Granulation mechanism To form grannulesbond must be formed

between powder particles So they adhere Bond should be strong to prevent break

down 5 bonding mechanism

Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild

particles Formation of solid bridges after

solvent evaporation

27 Mechanism of granule formation

Divided into 3 Nucleation Transition Ball growth

28 GRANULATION EQUIPMENTS

Single pot granulator

High shear mixture granulator

Fluid bed granulator

29

Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment

eg Single Pot Processor One-Pot Processor

30 Single pot granulator

31 Rapid mixer granulator

32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)

Liquid binder addition (Approx 1-2 mins)

Wet massing

Wet sieving of granules

Drying

Dry sieving of granules

33

Short processing time

Lesser amount of liquid binders required

Highly cohesive material can be granulated

Increase in temperature may cause chemical degradation of thermolabile material

Over wetting of granules can lead to

large size lumps formation

ADVANTAGES DISADVANTAGES

34 Fluid bed granulator

Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas

Granulating and drying can be completed in one

step inside the machine

35

-Homogeneous granules

---Gentle product handling

--Uniform spraying of all particles in the fluid bed

36 Advantages Reduces dust formation during

processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor

space requirements

DISADVANTAGES

The Fluid Bed cleaning is labor-intensive and time consuming

Difficulty of assuring reproducibility

37

Tablets Excipients

38

The common types of tabletrsquos excipients are described in the figure

Diluents

Binders $ adhesives

Disintegrants

Colours sweeten

ers $ flavors

39Diluent or filler Bulking agent

Increase size of the tablet Suitable for handling

Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate

40 Requirements for a good diluent

Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

7DIFFERENT TYPES OF TABLETS

(A) Tablets ingested orally 1 Compressed tablet eg Paracetamol

tablet 2 Multiple compressed tablet bull layered tablet bull Compression coated tablets

4 Delayed release tablet eg Enteric coated Bisacodyl

5 Sugar coated tablet eg Multivitamin tablet

6 Film coated tablet eg Metronidazole tablet

7 Chewable tablet eg Antacid tablet

8 Tablets used in oral cavity 1 Buccal tablet eg Vitamin-c tablet 2 Sublingual tablet eg Vicks Menthol

tablet 3 Troches or lozenges 4 Dental cone

9 (c) Tablets administered by other route 1 Implantation tablet 2 Vaginal tablet eg Clotrimazole tablet

(D) Tablets used to prepare solution

1 Effervescent tablet eg Dispirin tablet (Aspirin)

2 Dispensing tablet eg Enzyme tablet (Digiplex) 3 Hypodermic tablet

4 Tablet triturates eg Enzyme tablet (Digiplex)

10 TABLET GRANULATION

Granulation The process in which the primary powders particles are made adhere to form larger Multi particle entities called granulation

1

11Powders intended for compression into tablets

must possess two essential properties

Powder fluidity or flowabilitybull Powder flow can be improved mechanically by the

use of vibrators glidantPowder compressibilitybull The property of forming a stable intact

compact mass when pressure is applied is called powder compressibility

12ADVANTAGES OF GRANNULATION

bull To avoid powder segregation

bull To enhance the flow of powder

bull To produce uniform mixtures

bull To produce dust free formulations

bull To eliminate poor content uniformity

bull To improve compaction characteristics

of mix

13 Manufacturing of granules

Dry granulation method wet granulation method

Direct compression compression granulation Wet granulation

14Dry granulation

Compaction of powder

milling

screening

15 AdvantagesLess

equipments amp space

Eliminate need of binder

solution

Disadvantages

No uniform

color distributio

n

Process create

more dust

16Direct compression

Some Crystalline substances can compress directly Directly compressible diluent is an

Inert Compactable Maintain compression capacity even after adding disintegrates

and other ingredients Direct compression materials should posses

Good flow and compressibility Inert Tasteless Reworkable Inexpensive Able to disintegrate

17

DrugExcipientsDiluentsDisintegrantLarge sized tabletsSlugsGranulesDisintegrantGlidant

LubricanttabletsCompression granulation

Weighing

Mixing [blender]

Slugging[tablet press roller compactorScreening sieve[20-25]

Mixing

Compression [tablet press]

18

Important Steps1 Milling of drugs and excipients2 Mixing of ingredients3 Tablet compression

19 COMPRESSION GRANNULATION Dose of a drug is too high for its

compression Drug sensitive to heat and moisture Aspirin multi vitamins Compaction of components of tablets by

means of tablet press or machine Milling and screening prior to fluid

compression

20 Roller compactor

On a large scale compression granulation can also be performed on a roller compactor

Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch

21

It requires drugs or excipients with cohesive properties

Large particles must be used rarr (acceptable flowability and bulk density)

If the drug powder has low compatability it is difficult to form into tablets

Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose

LIMITATIONS OF DRY GRANULATION

22 WET GRANULATION

It involves massing of a mix of dry Primary powder particles using a Granulating fluid

The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol

The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying

23

bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening

24 Advantages of wet granulation

prevent segregation of the constituents of the powder blend

Improved cohesiveness and compressibility

To improve homogeneity Uniform distribution of contents and

colour The dissolution rate of hydrophobic

drugs may be improved by wet granulation method

25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive

drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to

migration of dyes during drying stage

EquipmentsTraditionally dry mixing in wet granulation

process has been carried out usingSigma blade mixerHeavy-duty planetary mixer

26Granulation mechanism To form grannulesbond must be formed

between powder particles So they adhere Bond should be strong to prevent break

down 5 bonding mechanism

Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild

particles Formation of solid bridges after

solvent evaporation

27 Mechanism of granule formation

Divided into 3 Nucleation Transition Ball growth

28 GRANULATION EQUIPMENTS

Single pot granulator

High shear mixture granulator

Fluid bed granulator

29

Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment

eg Single Pot Processor One-Pot Processor

30 Single pot granulator

31 Rapid mixer granulator

32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)

Liquid binder addition (Approx 1-2 mins)

Wet massing

Wet sieving of granules

Drying

Dry sieving of granules

33

Short processing time

Lesser amount of liquid binders required

Highly cohesive material can be granulated

Increase in temperature may cause chemical degradation of thermolabile material

Over wetting of granules can lead to

large size lumps formation

ADVANTAGES DISADVANTAGES

34 Fluid bed granulator

Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas

Granulating and drying can be completed in one

step inside the machine

35

-Homogeneous granules

---Gentle product handling

--Uniform spraying of all particles in the fluid bed

36 Advantages Reduces dust formation during

processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor

space requirements

DISADVANTAGES

The Fluid Bed cleaning is labor-intensive and time consuming

Difficulty of assuring reproducibility

37

Tablets Excipients

38

The common types of tabletrsquos excipients are described in the figure

Diluents

Binders $ adhesives

Disintegrants

Colours sweeten

ers $ flavors

39Diluent or filler Bulking agent

Increase size of the tablet Suitable for handling

Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate

40 Requirements for a good diluent

Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

8 Tablets used in oral cavity 1 Buccal tablet eg Vitamin-c tablet 2 Sublingual tablet eg Vicks Menthol

tablet 3 Troches or lozenges 4 Dental cone

9 (c) Tablets administered by other route 1 Implantation tablet 2 Vaginal tablet eg Clotrimazole tablet

(D) Tablets used to prepare solution

1 Effervescent tablet eg Dispirin tablet (Aspirin)

2 Dispensing tablet eg Enzyme tablet (Digiplex) 3 Hypodermic tablet

4 Tablet triturates eg Enzyme tablet (Digiplex)

10 TABLET GRANULATION

Granulation The process in which the primary powders particles are made adhere to form larger Multi particle entities called granulation

1

11Powders intended for compression into tablets

must possess two essential properties

Powder fluidity or flowabilitybull Powder flow can be improved mechanically by the

use of vibrators glidantPowder compressibilitybull The property of forming a stable intact

compact mass when pressure is applied is called powder compressibility

12ADVANTAGES OF GRANNULATION

bull To avoid powder segregation

bull To enhance the flow of powder

bull To produce uniform mixtures

bull To produce dust free formulations

bull To eliminate poor content uniformity

bull To improve compaction characteristics

of mix

13 Manufacturing of granules

Dry granulation method wet granulation method

Direct compression compression granulation Wet granulation

14Dry granulation

Compaction of powder

milling

screening

15 AdvantagesLess

equipments amp space

Eliminate need of binder

solution

Disadvantages

No uniform

color distributio

n

Process create

more dust

16Direct compression

Some Crystalline substances can compress directly Directly compressible diluent is an

Inert Compactable Maintain compression capacity even after adding disintegrates

and other ingredients Direct compression materials should posses

Good flow and compressibility Inert Tasteless Reworkable Inexpensive Able to disintegrate

17

DrugExcipientsDiluentsDisintegrantLarge sized tabletsSlugsGranulesDisintegrantGlidant

LubricanttabletsCompression granulation

Weighing

Mixing [blender]

Slugging[tablet press roller compactorScreening sieve[20-25]

Mixing

Compression [tablet press]

18

Important Steps1 Milling of drugs and excipients2 Mixing of ingredients3 Tablet compression

19 COMPRESSION GRANNULATION Dose of a drug is too high for its

compression Drug sensitive to heat and moisture Aspirin multi vitamins Compaction of components of tablets by

means of tablet press or machine Milling and screening prior to fluid

compression

20 Roller compactor

On a large scale compression granulation can also be performed on a roller compactor

Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch

21

It requires drugs or excipients with cohesive properties

Large particles must be used rarr (acceptable flowability and bulk density)

If the drug powder has low compatability it is difficult to form into tablets

Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose

LIMITATIONS OF DRY GRANULATION

22 WET GRANULATION

It involves massing of a mix of dry Primary powder particles using a Granulating fluid

The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol

The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying

23

bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening

24 Advantages of wet granulation

prevent segregation of the constituents of the powder blend

Improved cohesiveness and compressibility

To improve homogeneity Uniform distribution of contents and

colour The dissolution rate of hydrophobic

drugs may be improved by wet granulation method

25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive

drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to

migration of dyes during drying stage

EquipmentsTraditionally dry mixing in wet granulation

process has been carried out usingSigma blade mixerHeavy-duty planetary mixer

26Granulation mechanism To form grannulesbond must be formed

between powder particles So they adhere Bond should be strong to prevent break

down 5 bonding mechanism

Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild

particles Formation of solid bridges after

solvent evaporation

27 Mechanism of granule formation

Divided into 3 Nucleation Transition Ball growth

28 GRANULATION EQUIPMENTS

Single pot granulator

High shear mixture granulator

Fluid bed granulator

29

Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment

eg Single Pot Processor One-Pot Processor

30 Single pot granulator

31 Rapid mixer granulator

32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)

Liquid binder addition (Approx 1-2 mins)

Wet massing

Wet sieving of granules

Drying

Dry sieving of granules

33

Short processing time

Lesser amount of liquid binders required

Highly cohesive material can be granulated

Increase in temperature may cause chemical degradation of thermolabile material

Over wetting of granules can lead to

large size lumps formation

ADVANTAGES DISADVANTAGES

34 Fluid bed granulator

Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas

Granulating and drying can be completed in one

step inside the machine

35

-Homogeneous granules

---Gentle product handling

--Uniform spraying of all particles in the fluid bed

36 Advantages Reduces dust formation during

processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor

space requirements

DISADVANTAGES

The Fluid Bed cleaning is labor-intensive and time consuming

Difficulty of assuring reproducibility

37

Tablets Excipients

38

The common types of tabletrsquos excipients are described in the figure

Diluents

Binders $ adhesives

Disintegrants

Colours sweeten

ers $ flavors

39Diluent or filler Bulking agent

Increase size of the tablet Suitable for handling

Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate

40 Requirements for a good diluent

Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

9 (c) Tablets administered by other route 1 Implantation tablet 2 Vaginal tablet eg Clotrimazole tablet

(D) Tablets used to prepare solution

1 Effervescent tablet eg Dispirin tablet (Aspirin)

2 Dispensing tablet eg Enzyme tablet (Digiplex) 3 Hypodermic tablet

4 Tablet triturates eg Enzyme tablet (Digiplex)

10 TABLET GRANULATION

Granulation The process in which the primary powders particles are made adhere to form larger Multi particle entities called granulation

1

11Powders intended for compression into tablets

must possess two essential properties

Powder fluidity or flowabilitybull Powder flow can be improved mechanically by the

use of vibrators glidantPowder compressibilitybull The property of forming a stable intact

compact mass when pressure is applied is called powder compressibility

12ADVANTAGES OF GRANNULATION

bull To avoid powder segregation

bull To enhance the flow of powder

bull To produce uniform mixtures

bull To produce dust free formulations

bull To eliminate poor content uniformity

bull To improve compaction characteristics

of mix

13 Manufacturing of granules

Dry granulation method wet granulation method

Direct compression compression granulation Wet granulation

14Dry granulation

Compaction of powder

milling

screening

15 AdvantagesLess

equipments amp space

Eliminate need of binder

solution

Disadvantages

No uniform

color distributio

n

Process create

more dust

16Direct compression

Some Crystalline substances can compress directly Directly compressible diluent is an

Inert Compactable Maintain compression capacity even after adding disintegrates

and other ingredients Direct compression materials should posses

Good flow and compressibility Inert Tasteless Reworkable Inexpensive Able to disintegrate

17

DrugExcipientsDiluentsDisintegrantLarge sized tabletsSlugsGranulesDisintegrantGlidant

LubricanttabletsCompression granulation

Weighing

Mixing [blender]

Slugging[tablet press roller compactorScreening sieve[20-25]

Mixing

Compression [tablet press]

18

Important Steps1 Milling of drugs and excipients2 Mixing of ingredients3 Tablet compression

19 COMPRESSION GRANNULATION Dose of a drug is too high for its

compression Drug sensitive to heat and moisture Aspirin multi vitamins Compaction of components of tablets by

means of tablet press or machine Milling and screening prior to fluid

compression

20 Roller compactor

On a large scale compression granulation can also be performed on a roller compactor

Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch

21

It requires drugs or excipients with cohesive properties

Large particles must be used rarr (acceptable flowability and bulk density)

If the drug powder has low compatability it is difficult to form into tablets

Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose

LIMITATIONS OF DRY GRANULATION

22 WET GRANULATION

It involves massing of a mix of dry Primary powder particles using a Granulating fluid

The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol

The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying

23

bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening

24 Advantages of wet granulation

prevent segregation of the constituents of the powder blend

Improved cohesiveness and compressibility

To improve homogeneity Uniform distribution of contents and

colour The dissolution rate of hydrophobic

drugs may be improved by wet granulation method

25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive

drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to

migration of dyes during drying stage

EquipmentsTraditionally dry mixing in wet granulation

process has been carried out usingSigma blade mixerHeavy-duty planetary mixer

26Granulation mechanism To form grannulesbond must be formed

between powder particles So they adhere Bond should be strong to prevent break

down 5 bonding mechanism

Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild

particles Formation of solid bridges after

solvent evaporation

27 Mechanism of granule formation

Divided into 3 Nucleation Transition Ball growth

28 GRANULATION EQUIPMENTS

Single pot granulator

High shear mixture granulator

Fluid bed granulator

29

Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment

eg Single Pot Processor One-Pot Processor

30 Single pot granulator

31 Rapid mixer granulator

32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)

Liquid binder addition (Approx 1-2 mins)

Wet massing

Wet sieving of granules

Drying

Dry sieving of granules

33

Short processing time

Lesser amount of liquid binders required

Highly cohesive material can be granulated

Increase in temperature may cause chemical degradation of thermolabile material

Over wetting of granules can lead to

large size lumps formation

ADVANTAGES DISADVANTAGES

34 Fluid bed granulator

Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas

Granulating and drying can be completed in one

step inside the machine

35

-Homogeneous granules

---Gentle product handling

--Uniform spraying of all particles in the fluid bed

36 Advantages Reduces dust formation during

processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor

space requirements

DISADVANTAGES

The Fluid Bed cleaning is labor-intensive and time consuming

Difficulty of assuring reproducibility

37

Tablets Excipients

38

The common types of tabletrsquos excipients are described in the figure

Diluents

Binders $ adhesives

Disintegrants

Colours sweeten

ers $ flavors

39Diluent or filler Bulking agent

Increase size of the tablet Suitable for handling

Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate

40 Requirements for a good diluent

Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

10 TABLET GRANULATION

Granulation The process in which the primary powders particles are made adhere to form larger Multi particle entities called granulation

1

11Powders intended for compression into tablets

must possess two essential properties

Powder fluidity or flowabilitybull Powder flow can be improved mechanically by the

use of vibrators glidantPowder compressibilitybull The property of forming a stable intact

compact mass when pressure is applied is called powder compressibility

12ADVANTAGES OF GRANNULATION

bull To avoid powder segregation

bull To enhance the flow of powder

bull To produce uniform mixtures

bull To produce dust free formulations

bull To eliminate poor content uniformity

bull To improve compaction characteristics

of mix

13 Manufacturing of granules

Dry granulation method wet granulation method

Direct compression compression granulation Wet granulation

14Dry granulation

Compaction of powder

milling

screening

15 AdvantagesLess

equipments amp space

Eliminate need of binder

solution

Disadvantages

No uniform

color distributio

n

Process create

more dust

16Direct compression

Some Crystalline substances can compress directly Directly compressible diluent is an

Inert Compactable Maintain compression capacity even after adding disintegrates

and other ingredients Direct compression materials should posses

Good flow and compressibility Inert Tasteless Reworkable Inexpensive Able to disintegrate

17

DrugExcipientsDiluentsDisintegrantLarge sized tabletsSlugsGranulesDisintegrantGlidant

LubricanttabletsCompression granulation

Weighing

Mixing [blender]

Slugging[tablet press roller compactorScreening sieve[20-25]

Mixing

Compression [tablet press]

18

Important Steps1 Milling of drugs and excipients2 Mixing of ingredients3 Tablet compression

19 COMPRESSION GRANNULATION Dose of a drug is too high for its

compression Drug sensitive to heat and moisture Aspirin multi vitamins Compaction of components of tablets by

means of tablet press or machine Milling and screening prior to fluid

compression

20 Roller compactor

On a large scale compression granulation can also be performed on a roller compactor

Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch

21

It requires drugs or excipients with cohesive properties

Large particles must be used rarr (acceptable flowability and bulk density)

If the drug powder has low compatability it is difficult to form into tablets

Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose

LIMITATIONS OF DRY GRANULATION

22 WET GRANULATION

It involves massing of a mix of dry Primary powder particles using a Granulating fluid

The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol

The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying

23

bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening

24 Advantages of wet granulation

prevent segregation of the constituents of the powder blend

Improved cohesiveness and compressibility

To improve homogeneity Uniform distribution of contents and

colour The dissolution rate of hydrophobic

drugs may be improved by wet granulation method

25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive

drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to

migration of dyes during drying stage

EquipmentsTraditionally dry mixing in wet granulation

process has been carried out usingSigma blade mixerHeavy-duty planetary mixer

26Granulation mechanism To form grannulesbond must be formed

between powder particles So they adhere Bond should be strong to prevent break

down 5 bonding mechanism

Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild

particles Formation of solid bridges after

solvent evaporation

27 Mechanism of granule formation

Divided into 3 Nucleation Transition Ball growth

28 GRANULATION EQUIPMENTS

Single pot granulator

High shear mixture granulator

Fluid bed granulator

29

Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment

eg Single Pot Processor One-Pot Processor

30 Single pot granulator

31 Rapid mixer granulator

32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)

Liquid binder addition (Approx 1-2 mins)

Wet massing

Wet sieving of granules

Drying

Dry sieving of granules

33

Short processing time

Lesser amount of liquid binders required

Highly cohesive material can be granulated

Increase in temperature may cause chemical degradation of thermolabile material

Over wetting of granules can lead to

large size lumps formation

ADVANTAGES DISADVANTAGES

34 Fluid bed granulator

Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas

Granulating and drying can be completed in one

step inside the machine

35

-Homogeneous granules

---Gentle product handling

--Uniform spraying of all particles in the fluid bed

36 Advantages Reduces dust formation during

processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor

space requirements

DISADVANTAGES

The Fluid Bed cleaning is labor-intensive and time consuming

Difficulty of assuring reproducibility

37

Tablets Excipients

38

The common types of tabletrsquos excipients are described in the figure

Diluents

Binders $ adhesives

Disintegrants

Colours sweeten

ers $ flavors

39Diluent or filler Bulking agent

Increase size of the tablet Suitable for handling

Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate

40 Requirements for a good diluent

Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

1

11Powders intended for compression into tablets

must possess two essential properties

Powder fluidity or flowabilitybull Powder flow can be improved mechanically by the

use of vibrators glidantPowder compressibilitybull The property of forming a stable intact

compact mass when pressure is applied is called powder compressibility

12ADVANTAGES OF GRANNULATION

bull To avoid powder segregation

bull To enhance the flow of powder

bull To produce uniform mixtures

bull To produce dust free formulations

bull To eliminate poor content uniformity

bull To improve compaction characteristics

of mix

13 Manufacturing of granules

Dry granulation method wet granulation method

Direct compression compression granulation Wet granulation

14Dry granulation

Compaction of powder

milling

screening

15 AdvantagesLess

equipments amp space

Eliminate need of binder

solution

Disadvantages

No uniform

color distributio

n

Process create

more dust

16Direct compression

Some Crystalline substances can compress directly Directly compressible diluent is an

Inert Compactable Maintain compression capacity even after adding disintegrates

and other ingredients Direct compression materials should posses

Good flow and compressibility Inert Tasteless Reworkable Inexpensive Able to disintegrate

17

DrugExcipientsDiluentsDisintegrantLarge sized tabletsSlugsGranulesDisintegrantGlidant

LubricanttabletsCompression granulation

Weighing

Mixing [blender]

Slugging[tablet press roller compactorScreening sieve[20-25]

Mixing

Compression [tablet press]

18

Important Steps1 Milling of drugs and excipients2 Mixing of ingredients3 Tablet compression

19 COMPRESSION GRANNULATION Dose of a drug is too high for its

compression Drug sensitive to heat and moisture Aspirin multi vitamins Compaction of components of tablets by

means of tablet press or machine Milling and screening prior to fluid

compression

20 Roller compactor

On a large scale compression granulation can also be performed on a roller compactor

Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch

21

It requires drugs or excipients with cohesive properties

Large particles must be used rarr (acceptable flowability and bulk density)

If the drug powder has low compatability it is difficult to form into tablets

Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose

LIMITATIONS OF DRY GRANULATION

22 WET GRANULATION

It involves massing of a mix of dry Primary powder particles using a Granulating fluid

The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol

The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying

23

bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening

24 Advantages of wet granulation

prevent segregation of the constituents of the powder blend

Improved cohesiveness and compressibility

To improve homogeneity Uniform distribution of contents and

colour The dissolution rate of hydrophobic

drugs may be improved by wet granulation method

25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive

drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to

migration of dyes during drying stage

EquipmentsTraditionally dry mixing in wet granulation

process has been carried out usingSigma blade mixerHeavy-duty planetary mixer

26Granulation mechanism To form grannulesbond must be formed

between powder particles So they adhere Bond should be strong to prevent break

down 5 bonding mechanism

Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild

particles Formation of solid bridges after

solvent evaporation

27 Mechanism of granule formation

Divided into 3 Nucleation Transition Ball growth

28 GRANULATION EQUIPMENTS

Single pot granulator

High shear mixture granulator

Fluid bed granulator

29

Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment

eg Single Pot Processor One-Pot Processor

30 Single pot granulator

31 Rapid mixer granulator

32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)

Liquid binder addition (Approx 1-2 mins)

Wet massing

Wet sieving of granules

Drying

Dry sieving of granules

33

Short processing time

Lesser amount of liquid binders required

Highly cohesive material can be granulated

Increase in temperature may cause chemical degradation of thermolabile material

Over wetting of granules can lead to

large size lumps formation

ADVANTAGES DISADVANTAGES

34 Fluid bed granulator

Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas

Granulating and drying can be completed in one

step inside the machine

35

-Homogeneous granules

---Gentle product handling

--Uniform spraying of all particles in the fluid bed

36 Advantages Reduces dust formation during

processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor

space requirements

DISADVANTAGES

The Fluid Bed cleaning is labor-intensive and time consuming

Difficulty of assuring reproducibility

37

Tablets Excipients

38

The common types of tabletrsquos excipients are described in the figure

Diluents

Binders $ adhesives

Disintegrants

Colours sweeten

ers $ flavors

39Diluent or filler Bulking agent

Increase size of the tablet Suitable for handling

Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate

40 Requirements for a good diluent

Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

12ADVANTAGES OF GRANNULATION

bull To avoid powder segregation

bull To enhance the flow of powder

bull To produce uniform mixtures

bull To produce dust free formulations

bull To eliminate poor content uniformity

bull To improve compaction characteristics

of mix

13 Manufacturing of granules

Dry granulation method wet granulation method

Direct compression compression granulation Wet granulation

14Dry granulation

Compaction of powder

milling

screening

15 AdvantagesLess

equipments amp space

Eliminate need of binder

solution

Disadvantages

No uniform

color distributio

n

Process create

more dust

16Direct compression

Some Crystalline substances can compress directly Directly compressible diluent is an

Inert Compactable Maintain compression capacity even after adding disintegrates

and other ingredients Direct compression materials should posses

Good flow and compressibility Inert Tasteless Reworkable Inexpensive Able to disintegrate

17

DrugExcipientsDiluentsDisintegrantLarge sized tabletsSlugsGranulesDisintegrantGlidant

LubricanttabletsCompression granulation

Weighing

Mixing [blender]

Slugging[tablet press roller compactorScreening sieve[20-25]

Mixing

Compression [tablet press]

18

Important Steps1 Milling of drugs and excipients2 Mixing of ingredients3 Tablet compression

19 COMPRESSION GRANNULATION Dose of a drug is too high for its

compression Drug sensitive to heat and moisture Aspirin multi vitamins Compaction of components of tablets by

means of tablet press or machine Milling and screening prior to fluid

compression

20 Roller compactor

On a large scale compression granulation can also be performed on a roller compactor

Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch

21

It requires drugs or excipients with cohesive properties

Large particles must be used rarr (acceptable flowability and bulk density)

If the drug powder has low compatability it is difficult to form into tablets

Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose

LIMITATIONS OF DRY GRANULATION

22 WET GRANULATION

It involves massing of a mix of dry Primary powder particles using a Granulating fluid

The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol

The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying

23

bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening

24 Advantages of wet granulation

prevent segregation of the constituents of the powder blend

Improved cohesiveness and compressibility

To improve homogeneity Uniform distribution of contents and

colour The dissolution rate of hydrophobic

drugs may be improved by wet granulation method

25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive

drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to

migration of dyes during drying stage

EquipmentsTraditionally dry mixing in wet granulation

process has been carried out usingSigma blade mixerHeavy-duty planetary mixer

26Granulation mechanism To form grannulesbond must be formed

between powder particles So they adhere Bond should be strong to prevent break

down 5 bonding mechanism

Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild

particles Formation of solid bridges after

solvent evaporation

27 Mechanism of granule formation

Divided into 3 Nucleation Transition Ball growth

28 GRANULATION EQUIPMENTS

Single pot granulator

High shear mixture granulator

Fluid bed granulator

29

Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment

eg Single Pot Processor One-Pot Processor

30 Single pot granulator

31 Rapid mixer granulator

32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)

Liquid binder addition (Approx 1-2 mins)

Wet massing

Wet sieving of granules

Drying

Dry sieving of granules

33

Short processing time

Lesser amount of liquid binders required

Highly cohesive material can be granulated

Increase in temperature may cause chemical degradation of thermolabile material

Over wetting of granules can lead to

large size lumps formation

ADVANTAGES DISADVANTAGES

34 Fluid bed granulator

Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas

Granulating and drying can be completed in one

step inside the machine

35

-Homogeneous granules

---Gentle product handling

--Uniform spraying of all particles in the fluid bed

36 Advantages Reduces dust formation during

processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor

space requirements

DISADVANTAGES

The Fluid Bed cleaning is labor-intensive and time consuming

Difficulty of assuring reproducibility

37

Tablets Excipients

38

The common types of tabletrsquos excipients are described in the figure

Diluents

Binders $ adhesives

Disintegrants

Colours sweeten

ers $ flavors

39Diluent or filler Bulking agent

Increase size of the tablet Suitable for handling

Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate

40 Requirements for a good diluent

Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

13 Manufacturing of granules

Dry granulation method wet granulation method

Direct compression compression granulation Wet granulation

14Dry granulation

Compaction of powder

milling

screening

15 AdvantagesLess

equipments amp space

Eliminate need of binder

solution

Disadvantages

No uniform

color distributio

n

Process create

more dust

16Direct compression

Some Crystalline substances can compress directly Directly compressible diluent is an

Inert Compactable Maintain compression capacity even after adding disintegrates

and other ingredients Direct compression materials should posses

Good flow and compressibility Inert Tasteless Reworkable Inexpensive Able to disintegrate

17

DrugExcipientsDiluentsDisintegrantLarge sized tabletsSlugsGranulesDisintegrantGlidant

LubricanttabletsCompression granulation

Weighing

Mixing [blender]

Slugging[tablet press roller compactorScreening sieve[20-25]

Mixing

Compression [tablet press]

18

Important Steps1 Milling of drugs and excipients2 Mixing of ingredients3 Tablet compression

19 COMPRESSION GRANNULATION Dose of a drug is too high for its

compression Drug sensitive to heat and moisture Aspirin multi vitamins Compaction of components of tablets by

means of tablet press or machine Milling and screening prior to fluid

compression

20 Roller compactor

On a large scale compression granulation can also be performed on a roller compactor

Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch

21

It requires drugs or excipients with cohesive properties

Large particles must be used rarr (acceptable flowability and bulk density)

If the drug powder has low compatability it is difficult to form into tablets

Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose

LIMITATIONS OF DRY GRANULATION

22 WET GRANULATION

It involves massing of a mix of dry Primary powder particles using a Granulating fluid

The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol

The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying

23

bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening

24 Advantages of wet granulation

prevent segregation of the constituents of the powder blend

Improved cohesiveness and compressibility

To improve homogeneity Uniform distribution of contents and

colour The dissolution rate of hydrophobic

drugs may be improved by wet granulation method

25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive

drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to

migration of dyes during drying stage

EquipmentsTraditionally dry mixing in wet granulation

process has been carried out usingSigma blade mixerHeavy-duty planetary mixer

26Granulation mechanism To form grannulesbond must be formed

between powder particles So they adhere Bond should be strong to prevent break

down 5 bonding mechanism

Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild

particles Formation of solid bridges after

solvent evaporation

27 Mechanism of granule formation

Divided into 3 Nucleation Transition Ball growth

28 GRANULATION EQUIPMENTS

Single pot granulator

High shear mixture granulator

Fluid bed granulator

29

Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment

eg Single Pot Processor One-Pot Processor

30 Single pot granulator

31 Rapid mixer granulator

32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)

Liquid binder addition (Approx 1-2 mins)

Wet massing

Wet sieving of granules

Drying

Dry sieving of granules

33

Short processing time

Lesser amount of liquid binders required

Highly cohesive material can be granulated

Increase in temperature may cause chemical degradation of thermolabile material

Over wetting of granules can lead to

large size lumps formation

ADVANTAGES DISADVANTAGES

34 Fluid bed granulator

Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas

Granulating and drying can be completed in one

step inside the machine

35

-Homogeneous granules

---Gentle product handling

--Uniform spraying of all particles in the fluid bed

36 Advantages Reduces dust formation during

processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor

space requirements

DISADVANTAGES

The Fluid Bed cleaning is labor-intensive and time consuming

Difficulty of assuring reproducibility

37

Tablets Excipients

38

The common types of tabletrsquos excipients are described in the figure

Diluents

Binders $ adhesives

Disintegrants

Colours sweeten

ers $ flavors

39Diluent or filler Bulking agent

Increase size of the tablet Suitable for handling

Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate

40 Requirements for a good diluent

Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

14Dry granulation

Compaction of powder

milling

screening

15 AdvantagesLess

equipments amp space

Eliminate need of binder

solution

Disadvantages

No uniform

color distributio

n

Process create

more dust

16Direct compression

Some Crystalline substances can compress directly Directly compressible diluent is an

Inert Compactable Maintain compression capacity even after adding disintegrates

and other ingredients Direct compression materials should posses

Good flow and compressibility Inert Tasteless Reworkable Inexpensive Able to disintegrate

17

DrugExcipientsDiluentsDisintegrantLarge sized tabletsSlugsGranulesDisintegrantGlidant

LubricanttabletsCompression granulation

Weighing

Mixing [blender]

Slugging[tablet press roller compactorScreening sieve[20-25]

Mixing

Compression [tablet press]

18

Important Steps1 Milling of drugs and excipients2 Mixing of ingredients3 Tablet compression

19 COMPRESSION GRANNULATION Dose of a drug is too high for its

compression Drug sensitive to heat and moisture Aspirin multi vitamins Compaction of components of tablets by

means of tablet press or machine Milling and screening prior to fluid

compression

20 Roller compactor

On a large scale compression granulation can also be performed on a roller compactor

Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch

21

It requires drugs or excipients with cohesive properties

Large particles must be used rarr (acceptable flowability and bulk density)

If the drug powder has low compatability it is difficult to form into tablets

Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose

LIMITATIONS OF DRY GRANULATION

22 WET GRANULATION

It involves massing of a mix of dry Primary powder particles using a Granulating fluid

The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol

The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying

23

bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening

24 Advantages of wet granulation

prevent segregation of the constituents of the powder blend

Improved cohesiveness and compressibility

To improve homogeneity Uniform distribution of contents and

colour The dissolution rate of hydrophobic

drugs may be improved by wet granulation method

25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive

drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to

migration of dyes during drying stage

EquipmentsTraditionally dry mixing in wet granulation

process has been carried out usingSigma blade mixerHeavy-duty planetary mixer

26Granulation mechanism To form grannulesbond must be formed

between powder particles So they adhere Bond should be strong to prevent break

down 5 bonding mechanism

Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild

particles Formation of solid bridges after

solvent evaporation

27 Mechanism of granule formation

Divided into 3 Nucleation Transition Ball growth

28 GRANULATION EQUIPMENTS

Single pot granulator

High shear mixture granulator

Fluid bed granulator

29

Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment

eg Single Pot Processor One-Pot Processor

30 Single pot granulator

31 Rapid mixer granulator

32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)

Liquid binder addition (Approx 1-2 mins)

Wet massing

Wet sieving of granules

Drying

Dry sieving of granules

33

Short processing time

Lesser amount of liquid binders required

Highly cohesive material can be granulated

Increase in temperature may cause chemical degradation of thermolabile material

Over wetting of granules can lead to

large size lumps formation

ADVANTAGES DISADVANTAGES

34 Fluid bed granulator

Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas

Granulating and drying can be completed in one

step inside the machine

35

-Homogeneous granules

---Gentle product handling

--Uniform spraying of all particles in the fluid bed

36 Advantages Reduces dust formation during

processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor

space requirements

DISADVANTAGES

The Fluid Bed cleaning is labor-intensive and time consuming

Difficulty of assuring reproducibility

37

Tablets Excipients

38

The common types of tabletrsquos excipients are described in the figure

Diluents

Binders $ adhesives

Disintegrants

Colours sweeten

ers $ flavors

39Diluent or filler Bulking agent

Increase size of the tablet Suitable for handling

Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate

40 Requirements for a good diluent

Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

15 AdvantagesLess

equipments amp space

Eliminate need of binder

solution

Disadvantages

No uniform

color distributio

n

Process create

more dust

16Direct compression

Some Crystalline substances can compress directly Directly compressible diluent is an

Inert Compactable Maintain compression capacity even after adding disintegrates

and other ingredients Direct compression materials should posses

Good flow and compressibility Inert Tasteless Reworkable Inexpensive Able to disintegrate

17

DrugExcipientsDiluentsDisintegrantLarge sized tabletsSlugsGranulesDisintegrantGlidant

LubricanttabletsCompression granulation

Weighing

Mixing [blender]

Slugging[tablet press roller compactorScreening sieve[20-25]

Mixing

Compression [tablet press]

18

Important Steps1 Milling of drugs and excipients2 Mixing of ingredients3 Tablet compression

19 COMPRESSION GRANNULATION Dose of a drug is too high for its

compression Drug sensitive to heat and moisture Aspirin multi vitamins Compaction of components of tablets by

means of tablet press or machine Milling and screening prior to fluid

compression

20 Roller compactor

On a large scale compression granulation can also be performed on a roller compactor

Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch

21

It requires drugs or excipients with cohesive properties

Large particles must be used rarr (acceptable flowability and bulk density)

If the drug powder has low compatability it is difficult to form into tablets

Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose

LIMITATIONS OF DRY GRANULATION

22 WET GRANULATION

It involves massing of a mix of dry Primary powder particles using a Granulating fluid

The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol

The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying

23

bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening

24 Advantages of wet granulation

prevent segregation of the constituents of the powder blend

Improved cohesiveness and compressibility

To improve homogeneity Uniform distribution of contents and

colour The dissolution rate of hydrophobic

drugs may be improved by wet granulation method

25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive

drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to

migration of dyes during drying stage

EquipmentsTraditionally dry mixing in wet granulation

process has been carried out usingSigma blade mixerHeavy-duty planetary mixer

26Granulation mechanism To form grannulesbond must be formed

between powder particles So they adhere Bond should be strong to prevent break

down 5 bonding mechanism

Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild

particles Formation of solid bridges after

solvent evaporation

27 Mechanism of granule formation

Divided into 3 Nucleation Transition Ball growth

28 GRANULATION EQUIPMENTS

Single pot granulator

High shear mixture granulator

Fluid bed granulator

29

Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment

eg Single Pot Processor One-Pot Processor

30 Single pot granulator

31 Rapid mixer granulator

32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)

Liquid binder addition (Approx 1-2 mins)

Wet massing

Wet sieving of granules

Drying

Dry sieving of granules

33

Short processing time

Lesser amount of liquid binders required

Highly cohesive material can be granulated

Increase in temperature may cause chemical degradation of thermolabile material

Over wetting of granules can lead to

large size lumps formation

ADVANTAGES DISADVANTAGES

34 Fluid bed granulator

Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas

Granulating and drying can be completed in one

step inside the machine

35

-Homogeneous granules

---Gentle product handling

--Uniform spraying of all particles in the fluid bed

36 Advantages Reduces dust formation during

processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor

space requirements

DISADVANTAGES

The Fluid Bed cleaning is labor-intensive and time consuming

Difficulty of assuring reproducibility

37

Tablets Excipients

38

The common types of tabletrsquos excipients are described in the figure

Diluents

Binders $ adhesives

Disintegrants

Colours sweeten

ers $ flavors

39Diluent or filler Bulking agent

Increase size of the tablet Suitable for handling

Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate

40 Requirements for a good diluent

Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

16Direct compression

Some Crystalline substances can compress directly Directly compressible diluent is an

Inert Compactable Maintain compression capacity even after adding disintegrates

and other ingredients Direct compression materials should posses

Good flow and compressibility Inert Tasteless Reworkable Inexpensive Able to disintegrate

17

DrugExcipientsDiluentsDisintegrantLarge sized tabletsSlugsGranulesDisintegrantGlidant

LubricanttabletsCompression granulation

Weighing

Mixing [blender]

Slugging[tablet press roller compactorScreening sieve[20-25]

Mixing

Compression [tablet press]

18

Important Steps1 Milling of drugs and excipients2 Mixing of ingredients3 Tablet compression

19 COMPRESSION GRANNULATION Dose of a drug is too high for its

compression Drug sensitive to heat and moisture Aspirin multi vitamins Compaction of components of tablets by

means of tablet press or machine Milling and screening prior to fluid

compression

20 Roller compactor

On a large scale compression granulation can also be performed on a roller compactor

Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch

21

It requires drugs or excipients with cohesive properties

Large particles must be used rarr (acceptable flowability and bulk density)

If the drug powder has low compatability it is difficult to form into tablets

Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose

LIMITATIONS OF DRY GRANULATION

22 WET GRANULATION

It involves massing of a mix of dry Primary powder particles using a Granulating fluid

The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol

The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying

23

bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening

24 Advantages of wet granulation

prevent segregation of the constituents of the powder blend

Improved cohesiveness and compressibility

To improve homogeneity Uniform distribution of contents and

colour The dissolution rate of hydrophobic

drugs may be improved by wet granulation method

25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive

drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to

migration of dyes during drying stage

EquipmentsTraditionally dry mixing in wet granulation

process has been carried out usingSigma blade mixerHeavy-duty planetary mixer

26Granulation mechanism To form grannulesbond must be formed

between powder particles So they adhere Bond should be strong to prevent break

down 5 bonding mechanism

Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild

particles Formation of solid bridges after

solvent evaporation

27 Mechanism of granule formation

Divided into 3 Nucleation Transition Ball growth

28 GRANULATION EQUIPMENTS

Single pot granulator

High shear mixture granulator

Fluid bed granulator

29

Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment

eg Single Pot Processor One-Pot Processor

30 Single pot granulator

31 Rapid mixer granulator

32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)

Liquid binder addition (Approx 1-2 mins)

Wet massing

Wet sieving of granules

Drying

Dry sieving of granules

33

Short processing time

Lesser amount of liquid binders required

Highly cohesive material can be granulated

Increase in temperature may cause chemical degradation of thermolabile material

Over wetting of granules can lead to

large size lumps formation

ADVANTAGES DISADVANTAGES

34 Fluid bed granulator

Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas

Granulating and drying can be completed in one

step inside the machine

35

-Homogeneous granules

---Gentle product handling

--Uniform spraying of all particles in the fluid bed

36 Advantages Reduces dust formation during

processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor

space requirements

DISADVANTAGES

The Fluid Bed cleaning is labor-intensive and time consuming

Difficulty of assuring reproducibility

37

Tablets Excipients

38

The common types of tabletrsquos excipients are described in the figure

Diluents

Binders $ adhesives

Disintegrants

Colours sweeten

ers $ flavors

39Diluent or filler Bulking agent

Increase size of the tablet Suitable for handling

Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate

40 Requirements for a good diluent

Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

17

DrugExcipientsDiluentsDisintegrantLarge sized tabletsSlugsGranulesDisintegrantGlidant

LubricanttabletsCompression granulation

Weighing

Mixing [blender]

Slugging[tablet press roller compactorScreening sieve[20-25]

Mixing

Compression [tablet press]

18

Important Steps1 Milling of drugs and excipients2 Mixing of ingredients3 Tablet compression

19 COMPRESSION GRANNULATION Dose of a drug is too high for its

compression Drug sensitive to heat and moisture Aspirin multi vitamins Compaction of components of tablets by

means of tablet press or machine Milling and screening prior to fluid

compression

20 Roller compactor

On a large scale compression granulation can also be performed on a roller compactor

Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch

21

It requires drugs or excipients with cohesive properties

Large particles must be used rarr (acceptable flowability and bulk density)

If the drug powder has low compatability it is difficult to form into tablets

Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose

LIMITATIONS OF DRY GRANULATION

22 WET GRANULATION

It involves massing of a mix of dry Primary powder particles using a Granulating fluid

The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol

The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying

23

bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening

24 Advantages of wet granulation

prevent segregation of the constituents of the powder blend

Improved cohesiveness and compressibility

To improve homogeneity Uniform distribution of contents and

colour The dissolution rate of hydrophobic

drugs may be improved by wet granulation method

25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive

drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to

migration of dyes during drying stage

EquipmentsTraditionally dry mixing in wet granulation

process has been carried out usingSigma blade mixerHeavy-duty planetary mixer

26Granulation mechanism To form grannulesbond must be formed

between powder particles So they adhere Bond should be strong to prevent break

down 5 bonding mechanism

Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild

particles Formation of solid bridges after

solvent evaporation

27 Mechanism of granule formation

Divided into 3 Nucleation Transition Ball growth

28 GRANULATION EQUIPMENTS

Single pot granulator

High shear mixture granulator

Fluid bed granulator

29

Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment

eg Single Pot Processor One-Pot Processor

30 Single pot granulator

31 Rapid mixer granulator

32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)

Liquid binder addition (Approx 1-2 mins)

Wet massing

Wet sieving of granules

Drying

Dry sieving of granules

33

Short processing time

Lesser amount of liquid binders required

Highly cohesive material can be granulated

Increase in temperature may cause chemical degradation of thermolabile material

Over wetting of granules can lead to

large size lumps formation

ADVANTAGES DISADVANTAGES

34 Fluid bed granulator

Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas

Granulating and drying can be completed in one

step inside the machine

35

-Homogeneous granules

---Gentle product handling

--Uniform spraying of all particles in the fluid bed

36 Advantages Reduces dust formation during

processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor

space requirements

DISADVANTAGES

The Fluid Bed cleaning is labor-intensive and time consuming

Difficulty of assuring reproducibility

37

Tablets Excipients

38

The common types of tabletrsquos excipients are described in the figure

Diluents

Binders $ adhesives

Disintegrants

Colours sweeten

ers $ flavors

39Diluent or filler Bulking agent

Increase size of the tablet Suitable for handling

Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate

40 Requirements for a good diluent

Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

18

Important Steps1 Milling of drugs and excipients2 Mixing of ingredients3 Tablet compression

19 COMPRESSION GRANNULATION Dose of a drug is too high for its

compression Drug sensitive to heat and moisture Aspirin multi vitamins Compaction of components of tablets by

means of tablet press or machine Milling and screening prior to fluid

compression

20 Roller compactor

On a large scale compression granulation can also be performed on a roller compactor

Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch

21

It requires drugs or excipients with cohesive properties

Large particles must be used rarr (acceptable flowability and bulk density)

If the drug powder has low compatability it is difficult to form into tablets

Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose

LIMITATIONS OF DRY GRANULATION

22 WET GRANULATION

It involves massing of a mix of dry Primary powder particles using a Granulating fluid

The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol

The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying

23

bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening

24 Advantages of wet granulation

prevent segregation of the constituents of the powder blend

Improved cohesiveness and compressibility

To improve homogeneity Uniform distribution of contents and

colour The dissolution rate of hydrophobic

drugs may be improved by wet granulation method

25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive

drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to

migration of dyes during drying stage

EquipmentsTraditionally dry mixing in wet granulation

process has been carried out usingSigma blade mixerHeavy-duty planetary mixer

26Granulation mechanism To form grannulesbond must be formed

between powder particles So they adhere Bond should be strong to prevent break

down 5 bonding mechanism

Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild

particles Formation of solid bridges after

solvent evaporation

27 Mechanism of granule formation

Divided into 3 Nucleation Transition Ball growth

28 GRANULATION EQUIPMENTS

Single pot granulator

High shear mixture granulator

Fluid bed granulator

29

Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment

eg Single Pot Processor One-Pot Processor

30 Single pot granulator

31 Rapid mixer granulator

32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)

Liquid binder addition (Approx 1-2 mins)

Wet massing

Wet sieving of granules

Drying

Dry sieving of granules

33

Short processing time

Lesser amount of liquid binders required

Highly cohesive material can be granulated

Increase in temperature may cause chemical degradation of thermolabile material

Over wetting of granules can lead to

large size lumps formation

ADVANTAGES DISADVANTAGES

34 Fluid bed granulator

Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas

Granulating and drying can be completed in one

step inside the machine

35

-Homogeneous granules

---Gentle product handling

--Uniform spraying of all particles in the fluid bed

36 Advantages Reduces dust formation during

processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor

space requirements

DISADVANTAGES

The Fluid Bed cleaning is labor-intensive and time consuming

Difficulty of assuring reproducibility

37

Tablets Excipients

38

The common types of tabletrsquos excipients are described in the figure

Diluents

Binders $ adhesives

Disintegrants

Colours sweeten

ers $ flavors

39Diluent or filler Bulking agent

Increase size of the tablet Suitable for handling

Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate

40 Requirements for a good diluent

Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

19 COMPRESSION GRANNULATION Dose of a drug is too high for its

compression Drug sensitive to heat and moisture Aspirin multi vitamins Compaction of components of tablets by

means of tablet press or machine Milling and screening prior to fluid

compression

20 Roller compactor

On a large scale compression granulation can also be performed on a roller compactor

Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch

21

It requires drugs or excipients with cohesive properties

Large particles must be used rarr (acceptable flowability and bulk density)

If the drug powder has low compatability it is difficult to form into tablets

Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose

LIMITATIONS OF DRY GRANULATION

22 WET GRANULATION

It involves massing of a mix of dry Primary powder particles using a Granulating fluid

The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol

The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying

23

bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening

24 Advantages of wet granulation

prevent segregation of the constituents of the powder blend

Improved cohesiveness and compressibility

To improve homogeneity Uniform distribution of contents and

colour The dissolution rate of hydrophobic

drugs may be improved by wet granulation method

25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive

drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to

migration of dyes during drying stage

EquipmentsTraditionally dry mixing in wet granulation

process has been carried out usingSigma blade mixerHeavy-duty planetary mixer

26Granulation mechanism To form grannulesbond must be formed

between powder particles So they adhere Bond should be strong to prevent break

down 5 bonding mechanism

Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild

particles Formation of solid bridges after

solvent evaporation

27 Mechanism of granule formation

Divided into 3 Nucleation Transition Ball growth

28 GRANULATION EQUIPMENTS

Single pot granulator

High shear mixture granulator

Fluid bed granulator

29

Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment

eg Single Pot Processor One-Pot Processor

30 Single pot granulator

31 Rapid mixer granulator

32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)

Liquid binder addition (Approx 1-2 mins)

Wet massing

Wet sieving of granules

Drying

Dry sieving of granules

33

Short processing time

Lesser amount of liquid binders required

Highly cohesive material can be granulated

Increase in temperature may cause chemical degradation of thermolabile material

Over wetting of granules can lead to

large size lumps formation

ADVANTAGES DISADVANTAGES

34 Fluid bed granulator

Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas

Granulating and drying can be completed in one

step inside the machine

35

-Homogeneous granules

---Gentle product handling

--Uniform spraying of all particles in the fluid bed

36 Advantages Reduces dust formation during

processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor

space requirements

DISADVANTAGES

The Fluid Bed cleaning is labor-intensive and time consuming

Difficulty of assuring reproducibility

37

Tablets Excipients

38

The common types of tabletrsquos excipients are described in the figure

Diluents

Binders $ adhesives

Disintegrants

Colours sweeten

ers $ flavors

39Diluent or filler Bulking agent

Increase size of the tablet Suitable for handling

Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate

40 Requirements for a good diluent

Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

20 Roller compactor

On a large scale compression granulation can also be performed on a roller compactor

Granulation by dry compaction can also be achieved by passing powders between two rollers that compact the material at pressure of up to 10 tons per linear inch

21

It requires drugs or excipients with cohesive properties

Large particles must be used rarr (acceptable flowability and bulk density)

If the drug powder has low compatability it is difficult to form into tablets

Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose

LIMITATIONS OF DRY GRANULATION

22 WET GRANULATION

It involves massing of a mix of dry Primary powder particles using a Granulating fluid

The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol

The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying

23

bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening

24 Advantages of wet granulation

prevent segregation of the constituents of the powder blend

Improved cohesiveness and compressibility

To improve homogeneity Uniform distribution of contents and

colour The dissolution rate of hydrophobic

drugs may be improved by wet granulation method

25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive

drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to

migration of dyes during drying stage

EquipmentsTraditionally dry mixing in wet granulation

process has been carried out usingSigma blade mixerHeavy-duty planetary mixer

26Granulation mechanism To form grannulesbond must be formed

between powder particles So they adhere Bond should be strong to prevent break

down 5 bonding mechanism

Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild

particles Formation of solid bridges after

solvent evaporation

27 Mechanism of granule formation

Divided into 3 Nucleation Transition Ball growth

28 GRANULATION EQUIPMENTS

Single pot granulator

High shear mixture granulator

Fluid bed granulator

29

Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment

eg Single Pot Processor One-Pot Processor

30 Single pot granulator

31 Rapid mixer granulator

32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)

Liquid binder addition (Approx 1-2 mins)

Wet massing

Wet sieving of granules

Drying

Dry sieving of granules

33

Short processing time

Lesser amount of liquid binders required

Highly cohesive material can be granulated

Increase in temperature may cause chemical degradation of thermolabile material

Over wetting of granules can lead to

large size lumps formation

ADVANTAGES DISADVANTAGES

34 Fluid bed granulator

Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas

Granulating and drying can be completed in one

step inside the machine

35

-Homogeneous granules

---Gentle product handling

--Uniform spraying of all particles in the fluid bed

36 Advantages Reduces dust formation during

processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor

space requirements

DISADVANTAGES

The Fluid Bed cleaning is labor-intensive and time consuming

Difficulty of assuring reproducibility

37

Tablets Excipients

38

The common types of tabletrsquos excipients are described in the figure

Diluents

Binders $ adhesives

Disintegrants

Colours sweeten

ers $ flavors

39Diluent or filler Bulking agent

Increase size of the tablet Suitable for handling

Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate

40 Requirements for a good diluent

Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

21

It requires drugs or excipients with cohesive properties

Large particles must be used rarr (acceptable flowability and bulk density)

If the drug powder has low compatability it is difficult to form into tablets

Needs directly compressible filler that is usually expensive eg microcrystalline cellulose (Avicel) spray dried lactose

LIMITATIONS OF DRY GRANULATION

22 WET GRANULATION

It involves massing of a mix of dry Primary powder particles using a Granulating fluid

The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol

The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying

23

bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening

24 Advantages of wet granulation

prevent segregation of the constituents of the powder blend

Improved cohesiveness and compressibility

To improve homogeneity Uniform distribution of contents and

colour The dissolution rate of hydrophobic

drugs may be improved by wet granulation method

25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive

drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to

migration of dyes during drying stage

EquipmentsTraditionally dry mixing in wet granulation

process has been carried out usingSigma blade mixerHeavy-duty planetary mixer

26Granulation mechanism To form grannulesbond must be formed

between powder particles So they adhere Bond should be strong to prevent break

down 5 bonding mechanism

Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild

particles Formation of solid bridges after

solvent evaporation

27 Mechanism of granule formation

Divided into 3 Nucleation Transition Ball growth

28 GRANULATION EQUIPMENTS

Single pot granulator

High shear mixture granulator

Fluid bed granulator

29

Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment

eg Single Pot Processor One-Pot Processor

30 Single pot granulator

31 Rapid mixer granulator

32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)

Liquid binder addition (Approx 1-2 mins)

Wet massing

Wet sieving of granules

Drying

Dry sieving of granules

33

Short processing time

Lesser amount of liquid binders required

Highly cohesive material can be granulated

Increase in temperature may cause chemical degradation of thermolabile material

Over wetting of granules can lead to

large size lumps formation

ADVANTAGES DISADVANTAGES

34 Fluid bed granulator

Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas

Granulating and drying can be completed in one

step inside the machine

35

-Homogeneous granules

---Gentle product handling

--Uniform spraying of all particles in the fluid bed

36 Advantages Reduces dust formation during

processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor

space requirements

DISADVANTAGES

The Fluid Bed cleaning is labor-intensive and time consuming

Difficulty of assuring reproducibility

37

Tablets Excipients

38

The common types of tabletrsquos excipients are described in the figure

Diluents

Binders $ adhesives

Disintegrants

Colours sweeten

ers $ flavors

39Diluent or filler Bulking agent

Increase size of the tablet Suitable for handling

Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate

40 Requirements for a good diluent

Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

22 WET GRANULATION

It involves massing of a mix of dry Primary powder particles using a Granulating fluid

The fluid contain a solvent that must be Volatile and non-toxic eg water Ethanol

The granulating solvent may contain a Binding agent to ensure particle Adhesion after drying

23

bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening

24 Advantages of wet granulation

prevent segregation of the constituents of the powder blend

Improved cohesiveness and compressibility

To improve homogeneity Uniform distribution of contents and

colour The dissolution rate of hydrophobic

drugs may be improved by wet granulation method

25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive

drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to

migration of dyes during drying stage

EquipmentsTraditionally dry mixing in wet granulation

process has been carried out usingSigma blade mixerHeavy-duty planetary mixer

26Granulation mechanism To form grannulesbond must be formed

between powder particles So they adhere Bond should be strong to prevent break

down 5 bonding mechanism

Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild

particles Formation of solid bridges after

solvent evaporation

27 Mechanism of granule formation

Divided into 3 Nucleation Transition Ball growth

28 GRANULATION EQUIPMENTS

Single pot granulator

High shear mixture granulator

Fluid bed granulator

29

Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment

eg Single Pot Processor One-Pot Processor

30 Single pot granulator

31 Rapid mixer granulator

32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)

Liquid binder addition (Approx 1-2 mins)

Wet massing

Wet sieving of granules

Drying

Dry sieving of granules

33

Short processing time

Lesser amount of liquid binders required

Highly cohesive material can be granulated

Increase in temperature may cause chemical degradation of thermolabile material

Over wetting of granules can lead to

large size lumps formation

ADVANTAGES DISADVANTAGES

34 Fluid bed granulator

Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas

Granulating and drying can be completed in one

step inside the machine

35

-Homogeneous granules

---Gentle product handling

--Uniform spraying of all particles in the fluid bed

36 Advantages Reduces dust formation during

processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor

space requirements

DISADVANTAGES

The Fluid Bed cleaning is labor-intensive and time consuming

Difficulty of assuring reproducibility

37

Tablets Excipients

38

The common types of tabletrsquos excipients are described in the figure

Diluents

Binders $ adhesives

Disintegrants

Colours sweeten

ers $ flavors

39Diluent or filler Bulking agent

Increase size of the tablet Suitable for handling

Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate

40 Requirements for a good diluent

Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

23

bull End point is tested by pressing a portion of the mass in the palm if it crumbles (passed) under moderate pressure then the mixture is ready for wet screening

24 Advantages of wet granulation

prevent segregation of the constituents of the powder blend

Improved cohesiveness and compressibility

To improve homogeneity Uniform distribution of contents and

colour The dissolution rate of hydrophobic

drugs may be improved by wet granulation method

25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive

drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to

migration of dyes during drying stage

EquipmentsTraditionally dry mixing in wet granulation

process has been carried out usingSigma blade mixerHeavy-duty planetary mixer

26Granulation mechanism To form grannulesbond must be formed

between powder particles So they adhere Bond should be strong to prevent break

down 5 bonding mechanism

Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild

particles Formation of solid bridges after

solvent evaporation

27 Mechanism of granule formation

Divided into 3 Nucleation Transition Ball growth

28 GRANULATION EQUIPMENTS

Single pot granulator

High shear mixture granulator

Fluid bed granulator

29

Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment

eg Single Pot Processor One-Pot Processor

30 Single pot granulator

31 Rapid mixer granulator

32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)

Liquid binder addition (Approx 1-2 mins)

Wet massing

Wet sieving of granules

Drying

Dry sieving of granules

33

Short processing time

Lesser amount of liquid binders required

Highly cohesive material can be granulated

Increase in temperature may cause chemical degradation of thermolabile material

Over wetting of granules can lead to

large size lumps formation

ADVANTAGES DISADVANTAGES

34 Fluid bed granulator

Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas

Granulating and drying can be completed in one

step inside the machine

35

-Homogeneous granules

---Gentle product handling

--Uniform spraying of all particles in the fluid bed

36 Advantages Reduces dust formation during

processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor

space requirements

DISADVANTAGES

The Fluid Bed cleaning is labor-intensive and time consuming

Difficulty of assuring reproducibility

37

Tablets Excipients

38

The common types of tabletrsquos excipients are described in the figure

Diluents

Binders $ adhesives

Disintegrants

Colours sweeten

ers $ flavors

39Diluent or filler Bulking agent

Increase size of the tablet Suitable for handling

Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate

40 Requirements for a good diluent

Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

24 Advantages of wet granulation

prevent segregation of the constituents of the powder blend

Improved cohesiveness and compressibility

To improve homogeneity Uniform distribution of contents and

colour The dissolution rate of hydrophobic

drugs may be improved by wet granulation method

25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive

drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to

migration of dyes during drying stage

EquipmentsTraditionally dry mixing in wet granulation

process has been carried out usingSigma blade mixerHeavy-duty planetary mixer

26Granulation mechanism To form grannulesbond must be formed

between powder particles So they adhere Bond should be strong to prevent break

down 5 bonding mechanism

Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild

particles Formation of solid bridges after

solvent evaporation

27 Mechanism of granule formation

Divided into 3 Nucleation Transition Ball growth

28 GRANULATION EQUIPMENTS

Single pot granulator

High shear mixture granulator

Fluid bed granulator

29

Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment

eg Single Pot Processor One-Pot Processor

30 Single pot granulator

31 Rapid mixer granulator

32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)

Liquid binder addition (Approx 1-2 mins)

Wet massing

Wet sieving of granules

Drying

Dry sieving of granules

33

Short processing time

Lesser amount of liquid binders required

Highly cohesive material can be granulated

Increase in temperature may cause chemical degradation of thermolabile material

Over wetting of granules can lead to

large size lumps formation

ADVANTAGES DISADVANTAGES

34 Fluid bed granulator

Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas

Granulating and drying can be completed in one

step inside the machine

35

-Homogeneous granules

---Gentle product handling

--Uniform spraying of all particles in the fluid bed

36 Advantages Reduces dust formation during

processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor

space requirements

DISADVANTAGES

The Fluid Bed cleaning is labor-intensive and time consuming

Difficulty of assuring reproducibility

37

Tablets Excipients

38

The common types of tabletrsquos excipients are described in the figure

Diluents

Binders $ adhesives

Disintegrants

Colours sweeten

ers $ flavors

39Diluent or filler Bulking agent

Increase size of the tablet Suitable for handling

Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate

40 Requirements for a good diluent

Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

25Limitations of wet granulationbull Multiple separate steps are involvedbull Not suitable for heat and moisture sensitive

drugsbull It is an expensive process- bull Cannot be used for moisture sensitive drugsbull The use of soluble dyes often lead to

migration of dyes during drying stage

EquipmentsTraditionally dry mixing in wet granulation

process has been carried out usingSigma blade mixerHeavy-duty planetary mixer

26Granulation mechanism To form grannulesbond must be formed

between powder particles So they adhere Bond should be strong to prevent break

down 5 bonding mechanism

Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild

particles Formation of solid bridges after

solvent evaporation

27 Mechanism of granule formation

Divided into 3 Nucleation Transition Ball growth

28 GRANULATION EQUIPMENTS

Single pot granulator

High shear mixture granulator

Fluid bed granulator

29

Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment

eg Single Pot Processor One-Pot Processor

30 Single pot granulator

31 Rapid mixer granulator

32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)

Liquid binder addition (Approx 1-2 mins)

Wet massing

Wet sieving of granules

Drying

Dry sieving of granules

33

Short processing time

Lesser amount of liquid binders required

Highly cohesive material can be granulated

Increase in temperature may cause chemical degradation of thermolabile material

Over wetting of granules can lead to

large size lumps formation

ADVANTAGES DISADVANTAGES

34 Fluid bed granulator

Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas

Granulating and drying can be completed in one

step inside the machine

35

-Homogeneous granules

---Gentle product handling

--Uniform spraying of all particles in the fluid bed

36 Advantages Reduces dust formation during

processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor

space requirements

DISADVANTAGES

The Fluid Bed cleaning is labor-intensive and time consuming

Difficulty of assuring reproducibility

37

Tablets Excipients

38

The common types of tabletrsquos excipients are described in the figure

Diluents

Binders $ adhesives

Disintegrants

Colours sweeten

ers $ flavors

39Diluent or filler Bulking agent

Increase size of the tablet Suitable for handling

Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate

40 Requirements for a good diluent

Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

26Granulation mechanism To form grannulesbond must be formed

between powder particles So they adhere Bond should be strong to prevent break

down 5 bonding mechanism

Adhesion and cohesion Interfacial forces Mechanical interlocking Attractive forces between soild

particles Formation of solid bridges after

solvent evaporation

27 Mechanism of granule formation

Divided into 3 Nucleation Transition Ball growth

28 GRANULATION EQUIPMENTS

Single pot granulator

High shear mixture granulator

Fluid bed granulator

29

Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment

eg Single Pot Processor One-Pot Processor

30 Single pot granulator

31 Rapid mixer granulator

32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)

Liquid binder addition (Approx 1-2 mins)

Wet massing

Wet sieving of granules

Drying

Dry sieving of granules

33

Short processing time

Lesser amount of liquid binders required

Highly cohesive material can be granulated

Increase in temperature may cause chemical degradation of thermolabile material

Over wetting of granules can lead to

large size lumps formation

ADVANTAGES DISADVANTAGES

34 Fluid bed granulator

Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas

Granulating and drying can be completed in one

step inside the machine

35

-Homogeneous granules

---Gentle product handling

--Uniform spraying of all particles in the fluid bed

36 Advantages Reduces dust formation during

processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor

space requirements

DISADVANTAGES

The Fluid Bed cleaning is labor-intensive and time consuming

Difficulty of assuring reproducibility

37

Tablets Excipients

38

The common types of tabletrsquos excipients are described in the figure

Diluents

Binders $ adhesives

Disintegrants

Colours sweeten

ers $ flavors

39Diluent or filler Bulking agent

Increase size of the tablet Suitable for handling

Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate

40 Requirements for a good diluent

Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

27 Mechanism of granule formation

Divided into 3 Nucleation Transition Ball growth

28 GRANULATION EQUIPMENTS

Single pot granulator

High shear mixture granulator

Fluid bed granulator

29

Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment

eg Single Pot Processor One-Pot Processor

30 Single pot granulator

31 Rapid mixer granulator

32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)

Liquid binder addition (Approx 1-2 mins)

Wet massing

Wet sieving of granules

Drying

Dry sieving of granules

33

Short processing time

Lesser amount of liquid binders required

Highly cohesive material can be granulated

Increase in temperature may cause chemical degradation of thermolabile material

Over wetting of granules can lead to

large size lumps formation

ADVANTAGES DISADVANTAGES

34 Fluid bed granulator

Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas

Granulating and drying can be completed in one

step inside the machine

35

-Homogeneous granules

---Gentle product handling

--Uniform spraying of all particles in the fluid bed

36 Advantages Reduces dust formation during

processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor

space requirements

DISADVANTAGES

The Fluid Bed cleaning is labor-intensive and time consuming

Difficulty of assuring reproducibility

37

Tablets Excipients

38

The common types of tabletrsquos excipients are described in the figure

Diluents

Binders $ adhesives

Disintegrants

Colours sweeten

ers $ flavors

39Diluent or filler Bulking agent

Increase size of the tablet Suitable for handling

Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate

40 Requirements for a good diluent

Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

28 GRANULATION EQUIPMENTS

Single pot granulator

High shear mixture granulator

Fluid bed granulator

29

Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment

eg Single Pot Processor One-Pot Processor

30 Single pot granulator

31 Rapid mixer granulator

32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)

Liquid binder addition (Approx 1-2 mins)

Wet massing

Wet sieving of granules

Drying

Dry sieving of granules

33

Short processing time

Lesser amount of liquid binders required

Highly cohesive material can be granulated

Increase in temperature may cause chemical degradation of thermolabile material

Over wetting of granules can lead to

large size lumps formation

ADVANTAGES DISADVANTAGES

34 Fluid bed granulator

Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas

Granulating and drying can be completed in one

step inside the machine

35

-Homogeneous granules

---Gentle product handling

--Uniform spraying of all particles in the fluid bed

36 Advantages Reduces dust formation during

processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor

space requirements

DISADVANTAGES

The Fluid Bed cleaning is labor-intensive and time consuming

Difficulty of assuring reproducibility

37

Tablets Excipients

38

The common types of tabletrsquos excipients are described in the figure

Diluents

Binders $ adhesives

Disintegrants

Colours sweeten

ers $ flavors

39Diluent or filler Bulking agent

Increase size of the tablet Suitable for handling

Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate

40 Requirements for a good diluent

Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

29

Single pot granulation The granulation is done in a normal high shear processor and dried in same equipment

eg Single Pot Processor One-Pot Processor

30 Single pot granulator

31 Rapid mixer granulator

32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)

Liquid binder addition (Approx 1-2 mins)

Wet massing

Wet sieving of granules

Drying

Dry sieving of granules

33

Short processing time

Lesser amount of liquid binders required

Highly cohesive material can be granulated

Increase in temperature may cause chemical degradation of thermolabile material

Over wetting of granules can lead to

large size lumps formation

ADVANTAGES DISADVANTAGES

34 Fluid bed granulator

Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas

Granulating and drying can be completed in one

step inside the machine

35

-Homogeneous granules

---Gentle product handling

--Uniform spraying of all particles in the fluid bed

36 Advantages Reduces dust formation during

processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor

space requirements

DISADVANTAGES

The Fluid Bed cleaning is labor-intensive and time consuming

Difficulty of assuring reproducibility

37

Tablets Excipients

38

The common types of tabletrsquos excipients are described in the figure

Diluents

Binders $ adhesives

Disintegrants

Colours sweeten

ers $ flavors

39Diluent or filler Bulking agent

Increase size of the tablet Suitable for handling

Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate

40 Requirements for a good diluent

Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

30 Single pot granulator

31 Rapid mixer granulator

32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)

Liquid binder addition (Approx 1-2 mins)

Wet massing

Wet sieving of granules

Drying

Dry sieving of granules

33

Short processing time

Lesser amount of liquid binders required

Highly cohesive material can be granulated

Increase in temperature may cause chemical degradation of thermolabile material

Over wetting of granules can lead to

large size lumps formation

ADVANTAGES DISADVANTAGES

34 Fluid bed granulator

Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas

Granulating and drying can be completed in one

step inside the machine

35

-Homogeneous granules

---Gentle product handling

--Uniform spraying of all particles in the fluid bed

36 Advantages Reduces dust formation during

processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor

space requirements

DISADVANTAGES

The Fluid Bed cleaning is labor-intensive and time consuming

Difficulty of assuring reproducibility

37

Tablets Excipients

38

The common types of tabletrsquos excipients are described in the figure

Diluents

Binders $ adhesives

Disintegrants

Colours sweeten

ers $ flavors

39Diluent or filler Bulking agent

Increase size of the tablet Suitable for handling

Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate

40 Requirements for a good diluent

Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

31 Rapid mixer granulator

32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)

Liquid binder addition (Approx 1-2 mins)

Wet massing

Wet sieving of granules

Drying

Dry sieving of granules

33

Short processing time

Lesser amount of liquid binders required

Highly cohesive material can be granulated

Increase in temperature may cause chemical degradation of thermolabile material

Over wetting of granules can lead to

large size lumps formation

ADVANTAGES DISADVANTAGES

34 Fluid bed granulator

Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas

Granulating and drying can be completed in one

step inside the machine

35

-Homogeneous granules

---Gentle product handling

--Uniform spraying of all particles in the fluid bed

36 Advantages Reduces dust formation during

processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor

space requirements

DISADVANTAGES

The Fluid Bed cleaning is labor-intensive and time consuming

Difficulty of assuring reproducibility

37

Tablets Excipients

38

The common types of tabletrsquos excipients are described in the figure

Diluents

Binders $ adhesives

Disintegrants

Colours sweeten

ers $ flavors

39Diluent or filler Bulking agent

Increase size of the tablet Suitable for handling

Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate

40 Requirements for a good diluent

Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

32 High shear mixture granulationDry Powder mixing (Approx 2-5 mins)

Liquid binder addition (Approx 1-2 mins)

Wet massing

Wet sieving of granules

Drying

Dry sieving of granules

33

Short processing time

Lesser amount of liquid binders required

Highly cohesive material can be granulated

Increase in temperature may cause chemical degradation of thermolabile material

Over wetting of granules can lead to

large size lumps formation

ADVANTAGES DISADVANTAGES

34 Fluid bed granulator

Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas

Granulating and drying can be completed in one

step inside the machine

35

-Homogeneous granules

---Gentle product handling

--Uniform spraying of all particles in the fluid bed

36 Advantages Reduces dust formation during

processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor

space requirements

DISADVANTAGES

The Fluid Bed cleaning is labor-intensive and time consuming

Difficulty of assuring reproducibility

37

Tablets Excipients

38

The common types of tabletrsquos excipients are described in the figure

Diluents

Binders $ adhesives

Disintegrants

Colours sweeten

ers $ flavors

39Diluent or filler Bulking agent

Increase size of the tablet Suitable for handling

Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate

40 Requirements for a good diluent

Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

33

Short processing time

Lesser amount of liquid binders required

Highly cohesive material can be granulated

Increase in temperature may cause chemical degradation of thermolabile material

Over wetting of granules can lead to

large size lumps formation

ADVANTAGES DISADVANTAGES

34 Fluid bed granulator

Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas

Granulating and drying can be completed in one

step inside the machine

35

-Homogeneous granules

---Gentle product handling

--Uniform spraying of all particles in the fluid bed

36 Advantages Reduces dust formation during

processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor

space requirements

DISADVANTAGES

The Fluid Bed cleaning is labor-intensive and time consuming

Difficulty of assuring reproducibility

37

Tablets Excipients

38

The common types of tabletrsquos excipients are described in the figure

Diluents

Binders $ adhesives

Disintegrants

Colours sweeten

ers $ flavors

39Diluent or filler Bulking agent

Increase size of the tablet Suitable for handling

Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate

40 Requirements for a good diluent

Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

34 Fluid bed granulator

Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas

Granulating and drying can be completed in one

step inside the machine

35

-Homogeneous granules

---Gentle product handling

--Uniform spraying of all particles in the fluid bed

36 Advantages Reduces dust formation during

processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor

space requirements

DISADVANTAGES

The Fluid Bed cleaning is labor-intensive and time consuming

Difficulty of assuring reproducibility

37

Tablets Excipients

38

The common types of tabletrsquos excipients are described in the figure

Diluents

Binders $ adhesives

Disintegrants

Colours sweeten

ers $ flavors

39Diluent or filler Bulking agent

Increase size of the tablet Suitable for handling

Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate

40 Requirements for a good diluent

Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

35

-Homogeneous granules

---Gentle product handling

--Uniform spraying of all particles in the fluid bed

36 Advantages Reduces dust formation during

processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor

space requirements

DISADVANTAGES

The Fluid Bed cleaning is labor-intensive and time consuming

Difficulty of assuring reproducibility

37

Tablets Excipients

38

The common types of tabletrsquos excipients are described in the figure

Diluents

Binders $ adhesives

Disintegrants

Colours sweeten

ers $ flavors

39Diluent or filler Bulking agent

Increase size of the tablet Suitable for handling

Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate

40 Requirements for a good diluent

Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

36 Advantages Reduces dust formation during

processing reduces product loss Improves worker safetyprocess suitable to 1048708 Potent compounds Minimizing productoperator Exposure Minimizing cross contamination Reduced process time Reduced equipment and floor

space requirements

DISADVANTAGES

The Fluid Bed cleaning is labor-intensive and time consuming

Difficulty of assuring reproducibility

37

Tablets Excipients

38

The common types of tabletrsquos excipients are described in the figure

Diluents

Binders $ adhesives

Disintegrants

Colours sweeten

ers $ flavors

39Diluent or filler Bulking agent

Increase size of the tablet Suitable for handling

Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate

40 Requirements for a good diluent

Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

37

Tablets Excipients

38

The common types of tabletrsquos excipients are described in the figure

Diluents

Binders $ adhesives

Disintegrants

Colours sweeten

ers $ flavors

39Diluent or filler Bulking agent

Increase size of the tablet Suitable for handling

Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate

40 Requirements for a good diluent

Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

38

The common types of tabletrsquos excipients are described in the figure

Diluents

Binders $ adhesives

Disintegrants

Colours sweeten

ers $ flavors

39Diluent or filler Bulking agent

Increase size of the tablet Suitable for handling

Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate

40 Requirements for a good diluent

Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

39Diluent or filler Bulking agent

Increase size of the tablet Suitable for handling

Most common fillers in tablets1 Lactose2 Sugar or sugar alcohol (glucosesucrose sorbitol and mannitol)3 Cellulose and microcrystalline cellulose4 diCalcium phosphate dihydrate

40 Requirements for a good diluent

Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

40 Requirements for a good diluent

Chemically inert biocompatible cheap Non-hygroscopic Good biopharmaceutical properties water soluble or hydrophilic compatibility Have an acceptable taste

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

41 Disintegrants To ensure that the tablet when in contact

with a liquid breaks up into small fragments which promotes rapid drug dissolution

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

42Steps of the disintegration process

First The liquid wets the solid and penetrates the pores of the tablet

tablet breaks into smaller fragments

(aggregates of primary particles)

Second The aggregates will deaggregate into their primary powder particles

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

43 The Method of Disintegrant Addition

Mixed with other ingredients prior to granulation amp thus incorporated within the granules (INTRAGRANULAR ADDITION)

Mixed with the dry granules(EXTRA GRANULAR ADDITION)

Incorporated as both an intragranular and an extra granular portion

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

44 Commonly Used Disintegrants 1 Starch 2Cellulose (eg sodium carboxymethyl

cellulose)Typical concentration of 1-5 by weight 3 High swelling disintegrants(Modified Starch or Modified cellulose in concentration of 1-2

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

45 Binder Ensure that granules and tablets can be

formed with the required mechanical strength ( glue that holds powders together to form granules )

Eg- starch pasteGlucose Gelatin solutionAcaciaSucrose

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

46Incorporation of binder1 Dry Powder As dry powder mixed with other ingredient before

wet granulation As a dry powder in dry granulation (roller

compaction slugging)

2 Solution binder As a solution in wet granulation Binder can be added either dry with other

excipients for granulation or Already dissolved in the granulating fluid water is the most common granulating fluid

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

47 Typical binder concentration is 2 ndash 10 by weight

Binders can be Insoluble in water eg starch Soluble in water eg HPMC Soluble in water and ethanol

egPovidone

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

48 LUBRICANT

Lubricants prevent adherence of granulepowder to die wall and to promote smooth ejection from the die after compaction

Mechanisms of Action

1 Fluid lubrication 2 Boundary lubrication

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

49 1 Fluid lubrication A layer of fluid is located between the

moving surfaces separating them from each other amp thus reduces the friction

eg liquid paraffin

2 Boundary lubrication The sliding surfaces are separated by only a very

thin film of lubricant So the nature of the solid surfaces will therefore

affect friction

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

50

Disadvantages of lubricants 1 Lubricants tend to be hydrophobic

Under-lubricated blends tend to flow poorly and show compression sticking problems

Over-lubricated blends can adversely affect tablet hardness and dissolution rate as well as tablet strengthEg Magnesium Stearate Calcium Stearate Talc Stearic Acid Sodium Lauryl Sulfate liquid Paraffin propylene glycol (PG)

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

51 Glidant or flow aid Improve flowability of the powder added during direct compaction and to

granulation before tableting ( they reducing interparticulate friction)

Common Glidants are 1 Talc ( at concentration 1-2 ) 2 Colloidal silica ( 02

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

52 Antiadherent

Reduce adhesion between the powder and the punch faces amp thus prevent particles sticking to the punches due to excess moisture or engraved andor embossed punch face

Many lubricants such as magnesium stearate have also antiadherent properties

Also talc and starch can act as antiadherents

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

53 Sorbent

Are substances that are capable of sorbing some quantities of fluids in an apparently dry state

Thus oils or oil-drug solutions can be incorporated into a powder mixture which is granulated amp compacted into tablets

eg Microcrystalline cellulose amp silica

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

54 Flavor

Give the tablet a more pleasant taste or to mask an unpleasant one

Flavoring agents are often thermolabile and so cannot be added prior to an operation involving heat

They are often mixed with the granules as an alcohol solution

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

55 Colourent

It is added to tablets to aid identification and patient compliance

added during coating It can also be added prior to

compaction ( can be added as an insoluble powder or dissolved in the granulation liquid )

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

56Sweeteners

They are used in chewable tablet to exclude or limit the use of sugar in the tablets

Mannitol 72 as sweet as sucroseSaccharin 500 times sweeter than sucrose Disadvantage has a bitter taste after some time and carcinogenic Aspartame Largely replace

saccharin Disadv Lack of stability in the

presence of moisture

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

57

Tablet compression

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

58 Tablet Compression Machine

Hopper for holding and feeding granules or powder to be compressed

Dies that define the size and shape of the tablet

Punches for compressing the granules within the dies

A feeding mechanism for moving granules from the hopper into the dies

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

59

Tablet machine or tablet press

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

60 The compression cycle for a singlepunch tablet machine

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

61Stages of Tablet Formation(Compaction Cycle)

Gravitational flow of the powder from hopper via the die table into the die

(the die is closed at its lower end by the lower punch)

Tablet formation The upper punch descends enters the die the

powder isCompressed until a tablet is formed After maximum applied force is reachedthe upper

punch leaves the powder

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

62 Tablet ejection

The lower punch rises until its tip reaches the level of the top of the die

The tablet is subsequently removed from the die and die table by a pushing device

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

63 Tablet presses

Single punch Rotary press High speed rotary press Multi layer rotary press

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

64 Single Punch press (Eccentric Press)

Bench-top models that make one tablet

At a time (single-station presses) Disadvantages production of

small batches of tablets

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

65 Rotary Press( Multi station Press) (10 000 tablets per minute)

Large scale production It consists of a number of dies and sets of

punches ( from 3 up to 60) The dies are mounted in a circle in the die

table both the die and the punches rotate together

during operation of the machine

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

66

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

67 The powder is held in a hopper whose

lower opening is located just above the die table

The powder flows on to the die table amp fed into the die by a feed frame

During powder compression both punches operate by vertical movement

After tablet ejection the tablet is knocked away as the die passes the feed frame

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

68 Reference Text book of physical pharmacy by Tripathi pg no

210-263 Sherwood BE amp Becker JW (1998) ldquoA new class of

high-functionality excipients silici-fied microcrystalline celluloserdquo Pharm Tech 22 78ndash88

Vogel PJ Schmidt PC Force ndashTime Curves of a Modern Rotary Tablet Machine II Influence ofCompression Force and Tableting Speed on the Deformation Mechanisms of Pharmaceutical Substances Drug Dev Ind Pharm 1993 19 1917

The theory and practice of industrial pharmacy fourth edition by lachmanlieberman page no 449-543

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69

69

• TABLETS
• CONTENTS
• TABLETS (2)
• THE ADVANTAGES OF THE TABLET
• Slide 5
• DISADVANTAGES OF TABLET
• DIFFERENT TYPES OF TABLETS
• Slide 8
• Slide 9
• TABLET GRANULATION
• Slide 11
• ADVANTAGES OF GRANNULATION
• Manufacturing of granules
• Dry granulation
• Slide 15
• Direct compression
• Slide 17
• Slide 18
• COMPRESSION GRANNULATION
• Roller compactor
• LIMITATIONS OF DRY GRANULATION
• WET GRANULATION
• Slide 23
• Advantages of wet granulation
• Slide 25
• Granulation mechanism
• Mechanism of granule formation
• GRANULATION EQUIPMENTS
• Slide 29
• Single pot granulator
• Rapid mixer granulator
• High shear mixture granulation
• Slide 33
• Fluid bed granulator
• Slide 35
• Slide 36
• Tablets Excipients
• Slide 38
• Diluent or filler
• Requirements for a good diluent
• Disintegrants
• Steps of the disintegration process
• The Method of Disintegrant Addition
• Commonly Used Disintegrants
• Binder
• Incorporation of binder
• Slide 47
• LUBRICANT
• Slide 49
• Disadvantages of lubricants
• Glidant or flow aid
• Antiadherent
• Sorbent
• Flavor
• Colourent
• Sweeteners
• Tablet compression
• Tablet Compression Machine
• Tablet machine or tablet press
• The compression cycle for a single punch tablet machine
• Stages of Tablet Formation (Compaction Cycle)
• Tablet ejection
• Tablet presses
• Single Punch press (Eccentric Press)
• Rotary Press( Multi station Press)
• Slide 66
• Slide 67
• Reference
• Slide 69