Hard gelatin capsules

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MANUFACTURE OF HARD GELATIN SHELL
Presented ByMs.Surabhi Singh

• Guide Prof. Suresh G. Sudke

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INTRODUCTION

• Bad taste and objectionable odor were the major
  problem
• One piece capsule - FAB Moths and Dublauc (1834)
• Gelatin coated pills- Garot (1939)
• Two piece gelatin capsule- JCL Lehuby (1946)
• Taezet (French)- Palatable capsules
• F Hubel (America)- Low cost iron molds
• Eli-Lilly (1897) and Park Davis (1901)- Major
  manufacturer
• After 1930s and 1940s they were major supplier
  worldwide

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DEFINATION

• Capsules are unit solid dosage forms in which
  one or more medicinal and inert ingredients are
  enclosed in a small shell or container usually
  made of gelatin.

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TYPES
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PARTS OF HGC

• Body
• Cap

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ADVANTAGES

• Less compaction, rapid dissolution and better
  bioavailability
• Less adjuncts are required
• Economic
• Mask the unpleasant taste and odor of drugs
• Smooth, elegant and attractive in appearance
• Easy to swallow

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ADVANTAGES

• Shells are physiologically inert
• Easy to handle and carry
• Protect the drug from light
• Available in variety of colors
• Allow the filling of powder, granules, pellets,
  beads, semisolids, etc.

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DISADVANTAGES

• Not useful for hygroscopic and deliquescent drugs
• Not suitable for rapidly water soluble salts
• Shells sensitive to moisture
• Proven for microbial growth
• Potential stability problems
• Required specialized equipments to manufacture

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FORMULATION OF HGC SHELLS

• Gelatin
• Plasticizer
• Preservatives
• Colorants
• Opacifier
• Flavors
• Wetting agents
• Demineralized water

• .

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GELATIN

• Mixture of fractions of different molecular
  weight
• Molecular weight varying from 15,000 to 250,000
• Fractions of amino acids joined with peptide
  linkage
• Made from 18 different amino acids
• Predominant amino acids are alanine and glycine

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WHY ONLY GELATIN?

• Non-toxic, edible and widely used in foodstuffs
• Readily soluble in biological fluids
• Good strong, flexible, film-forming material
• Gelatin films are homogeneous in structure
• No allergic reactions
• Reversibly change from solution to gel

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TYPES OF GELATIN
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SOURCES OF GELATIN

• Collagens obtained from-
• Animal bones
• Hide portions
• Frozen pork skin
• Connective tissues

• Elemental analysis-
• Carbon 50.5
• Hydrogen 6.8
• Nitrogen 17.0
• Oxygen- 25.2

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PHARMAGEL A
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PHARMAGEL B
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PHYSICOCHEMICAL PROPERTIES OF GELATIN
Sr. No. Property Method Type A Type B
1 pH (1 solution) at 25C -- 3.8 6.0 5.0 7.4
2 Isoelectric point USP BP 9.0 9.2 8.9 9.2 4.8 5.0 4.8 5.2
3 Bloom strength (g) USP BP 75- 300 50 320 75 275 50 300
4 Viscosity (cPs) -- 2.0 7.5 2.0 7.5
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PHARMACOPOEIAL SPECIFICATION OF GELATIN
Sr. No. Test USP BP IP
1 Microbial limits
1a Total bacterial count lt 1000 -- NMT 1000
1b Salmonella species Negative Negative Negative
1c Escherichia coli Negative Negative Negative
2 Sulphur dioxide lt 0.15 lt 200 ppm NMT 200 ppm
3 Arsenic 0.8 lt 2 ppm NMT 2 ppm
4 Heavy metals lt 0.005 -- NMT 50 ppm
5 Copper -- lt 10 ppm --
6 Lead -- lt 5 ppm --
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PHARMACOPOEIAL SPECIFICATION OF GELATIN
Sr. No. Test USP BP IP
7 Zinc -- lt 25 ppm --
8 Iron lt 15 ppm -- --
9 Residue on ignition lt 2.0 lt 3.25 NMT3.25
10 Loss on drying -- lt16 NMT 16
11 pH -- 3.8- 7.6 3.8- 7.6
12 Bloom strength -- gt 150 g 150- 250 g
13 Odor Negative Positive Negative
14 Taste Negative Positive Negative
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PLASTICIZERS

• Maintain the flexibility of capsule shell
• For e.g. Glycerin, Sorbitol, etc.
• HGC shell ratio of Gelatin Glycerin is 0.41
• Ratio of Gelatin Glycerin determines hardness of
  shell

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PRESERVATIVES

• Employed to prevent microbial growth.
• Sorbic acid,
• Benzoic acid,
• Parabens (methyl paraben and propyl parabens)
• Sulfur dioxide (sodium bisulphite and sodium
  metabisulphite)

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COLORS
Improves the aesthetic values of the preparation
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COLORS (AZO DYES)
Sr. No. WHO Name FDA Name EEC No. CI No.
1 Allura Red AC FDC Red No. 40 -- --
2 Amaranth -- E123 16185
3 Azorubin -- E122 14720
4 Ponceau 4R -- E124 16255
5 Sunset Yellow FCF FDC Yellow No. 6 E110 15985
6 Tartrazine FDC Yellow No. 5 E102 19140
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COLORS (NON-AZO DYES)
Sr. No. WHO name FDA name EEC No. CI No.
7 Brilliant blue FCF FDC Blue No. 1 E133 42090
8 Erythrosine FDC Red No. 3 E127 45430
9 Indigo Carmine FDC Blue No. 2 E132 73015
10 Patent Blue V -- E131 42021
11 Quinoline Yellow DC Yellow No. 10 E104 47005
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OPACIFIER

• Render shell opaque
• Protects the drugs against light
• Hide the ingredients
• e.g. Titanium dioxide, calcium sulfate, etc.

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FLAVOURS

• Enhance the aesthetic value of capsules
• NMT 2
• Ethyl vanillin, essential oils, etc.

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WETTING AGENTS

• Ensure the uniform spreading of gelatin over pins
• Lubricates the metal molds
• The concentration of wetting agent is critical
• Sodium lauryl sulphate NMT 2

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STEPS IN HGC SHELL MFG

• Joining
• Sorting
• Printing
• Sealing and self locking

• Dipping
• Rotation/ Spinning
• Drying
• Stripping
• Trimming

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STEPS IN HGC SHELL MFG
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SHAPES

• .

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SIZES
Size Volume (ml) Fill powder weight (0.8 g/ml density) (g)
000 1.37 1.096
00 0.95 0.760
0 0.68 0.544
1 0.50 0.400
2 0.37 0.296
3 0.30 0.240
4 0.21 0.161
5 0.13 0.104
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QUALITY CONTROL TESTS

• Capsules are stored at 252C at 50 RH for 12
  hours before evaluation
• Average weight test
• Disintegration test
• Loss on drying
• Microbial limit
• Shell integrity test

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AVERAGE WEIGHT TEST (IP)
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AVERAGE WEIGHT TEST (IP)
Size Target weight (mg)
0 96 (86-106)
1 76 (68- 84)
2 63 (57- 69)
3 50 (45-55)
4 40 (36- 44)
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DISINTEGRATION TEST (IP)

• Comply disintegration tests for tablets and
  capsules using discs
• The shells disintegrates within 15 minutes

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MICROBIAL LIMIT TEST (IP)

• Total microbial count NMT 1000 per gram
• One gram of shell should be free from Salmonella
  species and Escherichia coli

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LOSS ON DRYING (IP)

• Use 0.3 g capsule shells for study
• Dry it in oven at 105C for 4 hours
• The target LOD value should be between (12.5 to
  16)

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SHELL INTEGRITY TEST

• Standard capsule shells stored at 252C and 50
  RH for 24 hours retains their original integrity.
• Standard capsule shells kept at 402C and 80 RH
  for 24 hours becomes soft, sticky and swollen

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RECENT ADVANCES

• Implants
• Floating capsules
• Delayed release capsules
• Protein and peptide delivery
• Pulsatile drug delivery in capsule form
• Colon targeted drug delivery (enzyme/ pressure
  sensitive polymers

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CONCLUSIONS

• HGC s are convenient to swallow .
• Capsules easily pass compendial tests
• Provides accuracy with uniformity of dosage.
• High speed filling rates of 1,00,000 capsules per
  hour
• A study (2010) showed that capsules were
  preferred over tablets by 90 participants

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THANK YOU