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INDEXINDEX

1. Introduction. 2. Hard Gelatin Capsule. 3. Hard Gelatin Capsule Machine. 4. Chemical Requirements.5. Gelatin. 6. Preparation of empty gelatin capsule. 7. Hard gelatin capsule machine. 8. Hard gelatin capsule.9. Hard Gelatin Capsule Filling. 10. Quality control of capsules. 11. Advantages and Disadvanages.

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CAPSULES: 

Capsules are solid dosage forms in which the drug substance is enclosed within either a hard or soft soluble shell, usually formed from gelatin. The term capsule is derived from the Latin word capsula, meaning a small container.

The first capsule prepared from gelatin was a one-piece capsule patented in France by Mothes and Du Blanc in 1834. Today capsules may be classified as either hard or soft, depending on the nature of the shell. Most capsules of both types are intended to be swallowed whole; however, some soft gelatine capsules are intended for rectal or vaginal insertion as suppositories.

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Hard Gelatin Capsule:Hard Gelatin Capsule: The hard gelatin capsule consists of two pieces in

the form of cylinders closed at one end. The shorter piece is called the cap. This cap fits over the open end of longer piece called body.

Hard gelatin capsules are also known as dry-filled capsules or two piece capsules. Hard gelatin capsules consists of two parts known as capsule body (longer part) and the capsule cap(the shorter part) The drug substance placed in the body and the caps are slided over it, hence enclosing the drug substance.

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• Cap

• Body

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Capsule Capsule sizesize

Body fill Body fill volumes volumes

Capsule size Body volume(ml)

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0.500.370.280.20

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FORMULATION OF HARD GELATIN FORMULATION OF HARD GELATIN SHELL : SHELL :

Gelatin: It is prepared by the hydrolysis of collagen obtained from animal connective tissue, bone and pork skin. There are two types of gelatin

Type A (Acid hydrolysis of pork skin) TypeB (Alkaline hydrolysis of bones)

The two types of gelatin can be distinguished by iso electric point as: Type A iso electric point near to PH 9 Type B iso electric point near to PH 4.7

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Certified Dyes : Colour approved by D & C act. Opacifiers: Tio2 Plasticizers: Sorbitol, Glycerin. Preservatives: Propyl and Methyl Parabens Sugar

Water - 12 to 16 % but may vary depending on the storage condition

Sulfur dioxide (15%) - prevent decomposition during manufacture

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Types of excipients used:Types of excipients used:

Powder-filled capsule

Diluents

Lubricants and Glidants

Wetting agents

Disintegrants

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MANUFACTURING OF CAPSULE SHELL :MANUFACTURING OF CAPSULE SHELL : Steps involved in making empty gelatin capsules - 1) Dipping 2) Spinning 3) Drying 4) Stripping 5) Trimming and Joining 6) polishing

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FILLING OF HARD GELATIN FILLING OF HARD GELATIN CAPSULES :CAPSULES : Various Filling Machines Available…

• Eli-lily and Co• Farmatic • Hofliger and Karg • Zanasi • Parke-Davis.• Macofar• capsuegel

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ZANASI AUTOMATICCAPSULE FILLING MACHINE

HOFLIGER KARG AUTOMATICCAPSULE FILLING MACHINE

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POWDERS GRANULES

BEADS TABLETS

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FILLING HARD CAPSULE SHELLS:FILLING HARD CAPSULE SHELLS:

A hand operated gelatin capsule filling machine consist of following parts:

• A bed with 200-300 holes.• A capsule loading tray.• A powder filling tray.• A pin plate having 200 or 300 pins corresponding to the number of holes in the bed and cap holding tray.• A lever handle.• A cam handle.• A plate fitted with rubber top.

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THE PROCESS OF WORKING:THE PROCESS OF WORKING:

Rectification.

Separating the caps from empty capsules.

Filling the bodies.

Scraping the excess powder.

Replacing the caps.

Sealing the capsules. Cleaning the outside of the filled capsules.

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RECTIFICATION :RECTIFICATION :

• The empty capsules are oriented so that all point the same direction i.e, body end downwards.

• In general capsule pass one at a time through a channel just wide enough to provide grip at cap end.

• The capsule will always be aligned body end downwards regardless of which end entered the channel first with the help of specially designated blades.

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SEPARATION OF CAPS FROM BODY :SEPARATION OF CAPS FROM BODY : • The rectified capsules are delivered body end first into the upper portion of split bushings or split filling rings.

• A vaccume applied from below pull the body down into the lower portion of the split bushing.

• The diameter of the bush is too large to allow them to follow body.

• The split bushing are separated to expose the bodies for filling.

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FILLING :FILLING :

• Auger fill principle : because the auger mounted in the hopper rotates at a constant rate, the rate of the delivery of the powder to the capsules tend to be constant.Flat blade auger – Screw auger E.g. capsule type8 filling machine.

Scraping the excess powder.

Replacing the caps.

Sealing the capsules.

Cleaning the outside of the filled capsules.

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LIQUID-FILL BASED FORMULATION LIQUID-FILL BASED FORMULATION ADVANCES AND CHALLENGES:ADVANCES AND CHALLENGES:

• This technology offers an inherently safer process than powder filled capsules and tablets for highly potent or cytotoxic drugs, as dust generation does not occur with liquid-fill formulations.

• The process involves the addition and mixing of the active substance in a liquid or molten vehicle (which could be a single excipient or a multi-component mix). The drug formulation is then filled into capsules, which can be sealed if necessary to prevent leakage.

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DUO CAP TECHNOLOGY :DUO CAP TECHNOLOGY : • Single oral capsule dosage units comprising capsule-in-a capsule technology such as Duocap offer a broad range of therapeutic applications.

• The inner and outer capsules may contain the same active drug, providing multiple release profiles from the dosage unit – for example, an immediate release formulation from the outer capsule and a controlled release formulation from the inner capsule.

• Alternatively, the inner and outer capsules may contain different actives for use with combination therapies or actives that are incompatible.

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A

b

C

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CFS 1000 semi industrial machine for filling liquid and semi solid formulation into two piece capsule and sealing.

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MICRO ENCAPSULATION :MICRO ENCAPSULATION :

• It is a process by which very tiny droplets / particles of liquid / solid materials are surrounded or coated with a continious film of polymeric material.• The primary reason m.e is found to either sustained/prolonged drug release.•Used for masking taste & odour of many drugs to improve patient compliance.• Drugs which are sensitive to oxygen, moisture, light, can be stabilized by M.E & Incomptability among drugs can be prevented• Many drugs have been en capsulated to reduce toxicity, GI irritation Ex. of coating material used for encapsulation water soluble resins : gelatin, pvp water insoluble resins : poly ethylene, cellulose nitrates. Waxes : Paraffin, Bees wax Enteric resins : shellac, cellulose acetate pthallate.

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FILLING POSSIBILITIES :FILLING POSSIBILITIES :

• By using hard gelatine capsule a variety of materials can be filled like powders, granules, pellets, liquids, semisolids, tablets etc

• It is probably by using capsugels conisnap capsules are worlds most popular brands of two piece gelatine capsules.

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1) Powders or granules2) pellet mixture3) paste4) capsule5) Tablet

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TYPICAL SHELL HARDNESS AND THEIR USES

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Quality control of Quality control of capsules:capsules:

1. Close length test. 2. Shape, size & Color. 3. Thickness of capsule shell 4. Content of API. 5. Weight variation test . 6. Uniformity of content. 7. Disintegration test. 8. Dissolution test. 9 . Stability test .

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AdvantagesAdvantages Easy to swallow. Masking capacity . Protection of medicament . Therapeutically inert & easy to digest . Easy to handle and carry . Different sizes are available. Product Identification. Provide enteric & sustained release effects. Moisture content . No need of complicated machinery Filling of incompatible substance in the same shell.

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DIS -ADVANTAGES :DIS -ADVANTAGES :

1. Highly soluble salts (e.g., iodides, bromides, and chlorides) generally should not be dispensed in hard gelatin capsules. Their rapid release may cause gastric irritation.

2. Filling equipment is slower than tableting.

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CONCLUSION :CONCLUSION :

• Capsules are more advantageous than the other dosage forms. Capsules contain drug in a liquid form having more advantages in the pharmaceutical field.

• The novel advances such as micro filling,enteric coating of hard gelatin capsules, Duo cap technology and material and machinery advances have been a significant improvement in the current days Hence capsules are the most preferred dosage forms than other conventional dosage forms.

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REFERENCE BOOKS :REFERENCE BOOKS :

• Leon lachman and HerbertA. Liberman The theory and practice of industrial pharmacy special Indian edition 2009 pg no 374 – 398 • Tapash K. Ghosh Bhaskara R jasti Theory and Practice of CONTEMPORARY PHARMACEUTICS EDITED BY pg no 314-323 • Edited by james swarbick Encyclopedia of pharmaceutical technology vol 1 3rd edition pg no 406-430 • Ansels pharmaceutical dosage forms and drug delivery system 8th edition pg no 204-226 • LA Augsburger (1995) “Hard and soft gelatin capsules” in Modern Pharmaceutics GS Banker & CT Rhodes, Eds., Marcel Dekker, Inc.: New York, NY, pp 395–440.

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