pilot plant capsules tablets es

8/10/2019 Pilot Plant Capsules Tablets ES

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PI LOT PLANT SCALE-UP

TECHNIQUES FOR CAPSULES

AND L IQUID ORALS

By: Praful Joshi


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Production considerations for

Capsules:

Materials

Method of production

Filling equipment


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Materials:

Gelatin

Plasticizers

Colorants

Opacifying agents

Preservative

Water


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Plasticizer:

- Plasticizer usedglycerin or sorbitol

- 5-10% is used in hard gelatin shell

- 10-15% is used in soft gelatin shell


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Colorants:

- Soluble dyes

-Insoluble dyes


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Opacifying Agents:

Titanium Dioxide (0.5%)


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Water:

Hot de-mineralized water is used in the preparation of dipping

solution.


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Method of production of

Gelatin:

Type A:

By acid hydrolysis: exhibits isoelectric

point at pH 9.0

Firmness

Type B:

By alkaline hydrolysis: exhibits

isoelectric point at pH 4.7Plasticity


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Method of production of

Gelatin:

Mixture of both the types of gelatin is used for

capsule manufacturing process reason being

availability and cost considerations Iron content in gelatin should not be more

than 15ppm if greater than 15ppm then it

reacts with color, shell and product

Gelatin viscosity should be 38 +/- 2 mps


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Type A Acid Hydrolysis:

Pork skin

Washed

1%-5% HCl10-30 hours

Acid removed

hot water extraction

Filter and vacuum

concentrated

Cooled to solidify

Air dryMill to size


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Type B Alkaline Hydrolysis:

Method-2:

Calf skin

Wash

10% Lime

6-12 weeks

Water wash

10-30 hours

Hot water extraction

Filter

Vacuumconcentration

Cooled to solidify

Air dry

Mill to size


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Manufactur ing of Hard Gelatin Capsules:

Gelatin gel of

Controlled viscosity is taken

Pins dipped for a particular

period of time

Gel sticks to the pin

Pins are spun for uniform

distribution of gel

Pins passed through

Drying chamber

Gel solidifies and is stripped

(removed)

Gel trimmed to particular length

(Body and Cap)

Joining of cap to body


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Encapsulation of Hard gelatin

capsules:

To produce capsules on high speed equipment, theprocessed powder blend must have the proper particlesize distribution and bulk density required to promotegood flow characteristics and to result in the formation of

compacts of the right size and sufficient cohesiveness tobe filled in the capsules

Physical properties - Bulk density, powder flowcharacteristics

Chemical Properties - prolonged trials of many hoursusing multiple batches are required for a process can be

judged as acceptable for routine production

The size and types of equipment may affect thegranulation properties


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Manufacture of Soft Gelatin Capsules:

Gelatin gelgelatin + plasticizer + water

Maintained at a particular temperature to remain as gel.

2 hoppers fill contents and gelatin (high temperature (930C)

molten state

flows easily)


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Gel passed between two compression roles (having depressions)

at cold temperature for solidification of gelatin

After gelatin is solidified gelatin ribbons are formed with

depressions and contents are filled into these depressions


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After the contents are filled sealing of the shells is done between

370C and 400C

Liquids should be filled at gravity at 350C

Oils, suspensions and semisolids can be encapsulated


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F il l ing equipments:

Eli Lilly, Indianapolis, Indiana

Parke-Davis, Detroit, Michigan

Hofliger and Karg, Waiblingen, Stuttgart, Germany

mG2 Macchine Automatiche, Pianoro, Italy

Fratelli Zanasi, Bologna, Italy

Cap-Fill Products, Ardmore, Pennsylvania

Dott Bonapace, Milano, Italy

Abbott Laboratories, North Chicago, Illinois

Hoffmann-La Roche, Nutley, New Jersey


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F il l ing operations:

Empty capsules

Formulation

Finishing

Special Techniques Imprinting, Sealing,

Capsule locking


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Processing conditions:

Humidity and temperature should be

controlled during manufacturing and storage

High Humidity

swelling of capsule shells,dimension increases

Low Humidity shrinking of capsule shells,

brittle and dimension decreases

High temperature

degradation of capsule

shells


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Evaluation of Capsules:

Following are the tests that should be carried out

for evaluation of the capsules

Uniformity of weight

Content of the active ingredients in thecapsules

Disintegration Test

Dissolution Test


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Production considerations in

L iquid Orals:

Tank Selection

Mixing and Dispersion

Filtration and Clarification

Transfer and Filling

Preservative Evaluation


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Tank Selection:

Depends on size, shape, working capacityand construction

Material used for tank construction should

not affect physical or chemical stabilityGlass-lined tanks are not used possibility of

breakage and thus contaminating theproduct

Magnetic SS interiors are used since particlesresulting from abrasion can be extractedfrom the bulk liquid by in-line magnets


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M ixing and Dispersion:

Mixing of wide variety of vehicles, suspending

agents, emulsifying agents, thickening agents

and flavoring agents employed in liquid

products makes the evaluation of mixing

equipment an important parameter in pilot

operation

Insertion of tank baffles or reduction inagitation speed are used in case of air

entrapment during mixing of viscous liquids


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F il tration and Clar i f ication:

Filtration an important parameter for ensuring the clarity in

the scale-up products

Pressurized filtration depending upon the viscosity, volume

and rate requirements


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Preservative Evaluation:

Preservative evaluation should be done in

addition to physical and chemical tests

Depending on the nature of the product anddegree of protection required carbon dioxide

or nitrogen can be overlaid during filling or

holding stages.

Bacteriological testing should be done, to knowif the concentration of preservative is to be

increased in the formulation


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Thank you

Seminar on Pilot Plant Scale-Up Techniques for Capsules andLiquid OralsBy Praful Joshi

Faculty: Dr. Bijaya Ghosh

pilot plant capsules tablets es

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