APT-Pilot Plant Techniques-Capsules & Liquid Orals

8/10/2019 APT-Pilot Plant Techniques-Capsules & Liquid Orals

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PILOT PLANT SCALE-UP

TECHNIQUES FORCAPSULES AND LIQUID

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 used glycerin 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 thepreparation 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 4.7 Plasticity


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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-1:

Dry bone or bone meal

Dicalcium phosphate and 5% HCl

10-15 days

10% Lime

4-8 weeks

Lime removal

pH adjustment

Hot water extraction

Filter

Vacuum concentration

Cooled to solidify

Air dry

Mill 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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Manufacture of Hard Gelatin

Capsules:

FFS Technology (Form Fill Seal)

Dipping

Spinning

Drying

Stripping

Trimming

Joining


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Manufacturing 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 the

granulation properties


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Manufacture of Soft Gelatin

Capsules:

Gelatin gel gelatin + 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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Manufacture of Soft Gelatin

Capsules:

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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Size of Capsules:

20 minim oblong

16 minim oval

9 minim round


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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

Filling equipments:


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Filling 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 capsuleshells


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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

Liquid 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 stability Glass-lined tanks are not used possibility of

breakage and thus contaminating the product

Magnetic SS interiors are used since

particles resulting from abrasion can beextracted from the bulk liquid by in-linemagnets


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Tank Selection:

Adequate clean-up procedures

developed

Valve assembly to be examined forcomplete drainage

For viscous liquids and suspensions

flush bottom valves are used to avoiddead spots


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Filtration and Clarification:

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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Transfer and Filling:

Filling important parameter in the

transfer of liquids from tank to tank and

into containers New batches should not be started until

the previous batches are completely

emptied from the tanks.


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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 and

degree 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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References:

The Theory and Practice of Industrial Pharmacy2ndEdition by Lieberman and Lachman

Pharmaceutical Sciences by Remington

Pharmaceutical Sciences by Cooper

Pharmaceutical Sciences by Tucker and HayesPharmaceutical Sciences by Tucker andRednick


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Thank you

Seminar on Pilot Plant Scale-Up Techniques forCapsules and Liquid Orals By Praful Joshi

Faculty: Dr. Bijaya Ghosh

Documents

APT-Pilot Plant Techniques-Capsules & Liquid Orals