MANUFACTURING OF GELATIN FILLING OF GELATIN CAPSULE HARD AND SOFT GELATIN CAPSULES

1. Capsules
By
Mr. Mohammad Ali
Assistant Professor
Dept. of Pharmaceutics,
Bharathi College of Pharmacy, Bharathinagar

2. Gelatin
Heterogeneous product derived by irreversible hydrolytic extraction of
treated animal collagen
Sources
Animal bones
Hide portions
Frozen pork skin
Types
Type A – derived from an acid treated precursor
isoelectric point in the region of pH 9.0
Type B – derived from an alkali treated precursor
isoelectric point in the region of pH 4.7

3. Manufacture of Gelatin
Dry Bone 5% HCl (10-15 days) 10% lime (4-8 weeks) Lime removal pH adj.
Calf Skin 10% Lime (6-12 weeks) Water wash(10-30 hrs)
Pork Skin 1-5% HCl (10-30 hrs) Acid removal
Hot Water Extraction (Extraction)
Filter (Filteration)
Vacuum Conc. (Evaporation under vacuum)
Cool to Solidify (Crystallization)
Air Dry (Drying)
Mill to size (Size reduction & Size separation)

4. Manufacture of Hard Gelatin Capsules
Dipping
Rotation
Drying
Stripping
Trimming
Joining
Sorting
Printing
Storage

5. Capsule Sizes
Sizes Fill weight in grams
000 1.096
00 0.760
0 0.544
1 0.400
2 0.296
3 0.240
4 0.168
5 0.104

6. Filling of Hard Gelatin Capsules

7. Steps Involved
Rectification
Separation of caps from bodies
Dosing of fill material
Replacement of caps
Ejection of filled capsules

8. Q C Tests
Content Uniformity
I. Determine content of active ingredient – 10 caps. – Average - less than 15% (85-
115%)- Passes
2 or more – over 15% & less than 25% - II
II. Determine content of AI in 20 more – Average of 30 caps – Not more than 3 over 15%
& less than 25% - (75-125%) Passes
Weight Variation
I. Wt. of 20 caps – Average – all less than 10% - (90-110%) Passes
1 or more out of limit (more than 10% and less than 25% – II
II. Wt. of intact cap – open, empty contents & weight empty caps – More than 3 deviates
– III
III. Wt. of 40 more – Average of 60 caps – Not more than 6 deviates - Passes
Disintegration
I. 6 – if 1 fails – 12 more – Not less than 16 of 18 should disintegrate – Passes
Dissolution

9. Soft Gelatin Capsule

10. Intro
Medicaments enclosed in a soft, soluble gelatin shells
Also known as Soft Elastic Capsules or Soft Gels
Advantages
Liq. To solid form
Dosage uniformity & accuracy
Bioavailability
Lesser irritation in stomach
Sealed – suit able for liquid and volatile drugs
Atmospheric oxidation is prevented
Elegant in appearance
Can be prepared as Suppositories or Pessaries
Breath fresheners, perfumes, bath oils, suntan oils and skin
creams

11. Disadvantages
Limited no. of firms have the filling facility
Expensive when compared to direct compression tabs.
Intimate contact with the shell – oily vehicles-proteolytic effect
Not suitable for water miscible and volatile liquids – migrate into hydrophilic shell
Glycerin and PG cannot be the major constituent – Soften the gelatin
Not suited for acidic subs. – Hydrolysis and leakage
Not suited for alkaline subs. – Tan the shell and affect solubility
Substances not stable in the presence of moisture
Formulation of Soft Gelatin Shell
Gelatin
Water
Plasticizers –glycerin, sorbitol, propylene glycol
Coloring agents – H2O soluble dyes, lakes, pigments, veg. colors
Opacifying agents – Titanium dioxide
Flavouring agents – Ethyl vanillin, essential oils (not more than 2%)
Sweetening agents – Sucrose (not more than 5%)
Preservatives – Methyl & Propyl paraben, Sod. metabisulphite, Pot. Bisulphite
Acids – Fumaric acid to aid solubility

12. Manufacture of Soft Gelatin Capsules

13. Methods
Plate process
Accogel process
Bubble process
Rotary die process

14. Plate Process
 Set of moulds used
 Warm sheet of G placed on lower plate
 Vacuum applied below – sheet drawn into the die pocket
 Pockets filled with material
 2nd sheet of G placed over content
 Place plate of mould over
 Place under the press and pressure applied to form caps.
 Wash with vol. solvent

15. Accogel Process
 Consists of Measuring roll, Die roll, Sealing roll
 Liquid flows by Gravity

16. Bubble Process
Consists of Concentric tube dispenser

18. Rotary Die Process

19. Popularly used
Formation of Gelatin sheet, Filling & Sealing –
Simultaneous
Steps Involved
Preparation of Gelatin soln.
Preparation of materials
Process
Printing
Finishing / Washing
Storage – Closed containers at 45% RH and
21-24 °C
Packaging – Blister (or) Glass/Plastic containers
Rotary Die Process

20. QC Tests
Stability Test – 20-30% RH; 21-24 C Includes
Includes: 1). Shell integrity 2). Determination of Shelf life
Weight variation
Content uniformity
Assay the contents: 9 of 10 – 85 to 115%
if not: further 20 – not less than 27 – 85 to 115%
Disintegration
Dissolution
Diameter