pilot plant for tablet dosage form

PILOT SCALE-UP FOR TABLET DOSAGE FORM

Presented by Shikha singhMCOPS Manipal university

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DEFINED AS A PART OF THE PHARMACEUTICAL INDUSTRY WHERE A LAB SCALE FORMULA IS TRANSFORMED INTO A VIABLE PRODUCT BY THE DEVELOPMENT OF LIABLE PRACTICAL PROCEDURE FOR MANUFACTURE

Presentaion by - Shikha Y Singh

R & D

Pilot Plant

Production

PILOT SCALE-UP

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Presentaion by - Shikha Y SinghOBJECTIVES

To produce physically

and chemically

stable therapeutic

dosage forms.

Review of the

processing equipment

Guidelines for

production and process

control

Evaluation and

validation

To identify

the critical

features of the

process

To provide master

manufa-cturing formula

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REPORTING RESPONSIBILITY:

Effective, economically, consistently reproducible on a production scale

Cost of manufacture: since low production costs provide a competitive advantage.

Each unit operation is optimised.


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PERSONNEL REQUIREMENTS: Scientists with experience in pilot plant

operations as well as in actual production area are the most preferable.

As they have to understand the intent of the formulator as well as understand the perspective of the production personnel.

The group should have some personnel with engineering knowledge as well as scale up also involves engineering principles.

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SPACE REQUIREMENTS:

Physical testing area

Standard equipment floor space

Storage area

Space for cleaning of equipments


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REVIEW OF FORMULA:Ingredients Quantity per

tablet (mg)Aminophylline 100

Tricalcium phosphate

50

Pregelatinized starch

15

Water

q.s.

Talc

30

Mineral oil, light

2

: Aminophylline tablets

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RAW MATERIALS:

Intermediate- or large-scale operations, materials handling- IMPORTANT

Prevent cross contamination. Accurate delivery of drug More sophisticated methods of handling

materials E.g-vacuum loading systems, metering pumps,

screw feed system.

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RELEVANT PROCESSING EQUIPMENTS: Relevant processing equipment used in different

stages of tablet operations: Material handling Dry blending Granulation Drying Reduction of particle size compression Direct compression Tablet coating


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DRY BLENDING

To ensure good distribution

Inadequate blending- drug content variation

To ensure no lumps or agglomerates- otherwise flow problem

Screening, milling of the ingredients makes the process- more reliable and reproducible


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EQUIPMENT USED

V-Blender Double cone Blender Ribbon Blender Slant cone Blender Bin Blender Orbiting Screw Blenders

vertical & horizontal high intensity mixers


14Ribbon BlenderDouble Cone Blender

Slant Cone Blender Bin Blender

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GRANULATION

To impart good flow properties to the material

To increase the apparent density of the powders

To change the particle size distribution Uniform dispersion of active ingredient

Equipment Used :1.Sigma blade mixer2.Heavy duty planetary

mixerWet methods

1.Roller Compaction mill 2.Shear millDry methods


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Sigma Blade Mixer

Planetary Mixer

Roller MillRotary Shear


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DRYING

Conventional method-hot air oven Factors to be considered during scale-up: Airflow Air temperature Depth of the granulation Granulation bed Too deep Process-Inefficient Too dense


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EQUIPMENT USED

TRAY DRYER (8 hour) FLUIDIZED BED DRYER (1 hour)

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REDUCTION OF PARTICLE SIZE: (SIZING)

Compression factor gets affected by particle size distribution are

Followability Compressibility Uniformity of tablet weight Content uniformity Tablet hardness Tablet colour uniformity


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Hammer Mill

Mechanical Sieving

Oscillating Granulator

EQUIPMENT USED

Or some screening devices


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COMPRESSION FUNCTIONS: Filling of empty die cavity with

granulation Pre-compression of granulation Compression of granulation Ejection of the tablet from the die

cavity ADVANCES- better control of Feeder mechanism Pre-compression Compression force


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Single Rotary Press

Double Rotary Press

EQUIPMENT USED

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TABLET COATING

3 important techniques involved in coating:

Sugar Coating modifications: conventional pan perforated pan/ FB columns

Film Coating Enteric Coating

Sugar coating

Solvent film coating

Aq. Film coating


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Coating PansAccela Coata

Dria CoaterFluidized Bed Coating

EQUIPMENT USED

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PRODUCTION RATES:

Timescale for a pharmaceutical tablet to be produced-fraction of a second

Production rate is around 10,000 tablets/minute Technical innovations- improved production

rates to more than 500,000 tablets/hour High rate of tablet output of modern presses

requires continuous tablet weight monitoring Electronic monitoring devices such as Thomas

Tablet Sentinel, Pharmakontroll or Killan control System-MC.

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PROCESS EVALUATION:

PARAMETERS

General appearance

Weight variation

Disintegration test

Dissolution Test Heating and coolingRates

Friability test

Content uniformitytest

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Presentaion by - Shikha Y SinghPREPARATION OF MASTER MANUFACTURING PROCESS:

Weight sheet

Processing directions

Manufacturing procedure

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Presentaion by - Shikha Y SinghGMP CONSIDERATIONS:

General

Sifting, Mixing and GranulationCompressions

Coating

Printing

Packaging (Strip and Blister)

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TRANSFER OF ANALYTICAL METHOD TO QUALITY ASSURANCE:

Scale-up of a new product- analytic test methods developed

Steps involved in transfer process: Review the process Proper analytical instrumentation is available Personnel are trained to perform the tasks Recovery studies Validation studies


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ANY QUERIES???


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pilot plant for tablet dosage form

Health & Medicine