10 Crucial Factors in Formulation of Hard Gelatin Capsule

Formulation of Hard Gelatin Capsule

Hard Gelatin Capsules (HGC)

1. Hard gelatin capsules are used for enclosing solid medicament or dry powders of drug substance.
2. It is also known as dry filled capsule.
3. They are less flexible and consist of cap and body. The cap is short while body is long.
4. It is available in different sizes, shapes and colours.
5. Hard gelatine capsule are hygroscopic in nature.

Primary Ingredients in Hard Gelatin Capsule

Formulation of Hard Gelatin Capsule required the following primary ingredients-

Gelatin

1. Gelatin is a tasteless, odourless protein substance which is extracted by boiling the skin, tendons, ligaments, bones of ox and pig.
2. There are two types of gelatine: Type A which is produced by acid-catalyzed hydrolysis and Type B which is produced by alkali -catalyzed hydrolysis.
3. Due to non toxic nature gelatin is widely used in food industry.
4. Gelatin is readily soluble in biological fluid and it also has good film forming properties.
5. The molecular weight of gelatin is 15000-250000.

Plasticizers

1. Plasticizers are additives that increase the plasticity or fluidity of a material.
2. It provides structural integrity to the gelatin so the capsule can maintain its shape.
3. The amount of plasticizers determines the rubbery texture of the capsule.
4. Sorbitol and glycerin are the most commonly used plasticizers in HGC.
5. Primary Ingredients in HGC

Other components

1. Other components of HGC are colouring agents, preservatives such as methyl paraben, lubricants such as stearic acid and surface treatment agents.
2. Titanium dioxide (TiO₂) may also be included for opacifying effects.
3. Opaque capsules are used to provide protection against light or to conceal the contents.

Parts of Hard Gelatin Capsule

Formulation of Hard Gelatin Capsule

1. The major component of HGC is gelatin.
2. Gelatin manufacturing involves organic reactions and thus its preparation is a time consuming process and may require many weeks to complete the processing.
3. Previously gelatin capsules were fabricated by pharmaceutical manufacturers but currently, capsule shell production is done by third party suppliers.

Gelatin solution

• Capsule production is an automated operation that begins with solubilizing the dry gelatin with a mixture of plasticizer and purified water.
• The gelatin solution is heated and transferred to a dip pan or pot which holds specific amount of hot gelatin at particular temperature.
• The amount of gelatin in pot is maintained automatically by controlling flow from hopper.

Dipping

• In this process, stainless steel pins are submersed in the heated gelatin solution to simultaneously form caps and bodies.
• The pins are maintained at 20 – 22°C, whereas the dipping solution is maintained at 50°C in a heated, jacketed dipping pan.
• The length time to cast the film is about 12 sec.
• During production, the thickness of the capsule wall is controlled by the viscosity of the gelatin solution, speed and time of dipping.

Spinning

• After dipping, pins are elevated and spinned to uniformly distribute the gelatin over the surface to avoid the formation of a bead at the capsule ends.
• This operation is performed until pins are facing upward.

Drying

• Blasts of cool air, which dry and solidify the capsules, is the next operation.
• The viscous gelatin is allowed to dry on the pins (about 100 pairs of pins/mould) and when dry these are removed from the pins.

Stripping

• A series of bronze jaws are used to strip the cap and body capsules from the pins.
• Capsules are rotated on a fixed clamping device to keep them in parts of the place.

Trimming

• Once the capsules are dry, they are separated from the pins by a set of mechanical jaws.
• The stripped cap and body parts are further trimmed to the required length using stationary knives.
• The stripped cap and body parts are delivered to a collector where they are firmly held together.
• As collector rotate, knives trims shells to the required length.

Joining

• After trimming to the right length, the cap and body are aligned concentrically in channels and the two portions are slowly pushed together to join them.
• The joined whole empty capsule is ejected from the machine.

Polishing

• Empty capsules are polished in pan. Acela-cota pan is used to de-dust and polish.
• Capsules are rubbed with cloth to make surface smooth.

Brushing

• Capsules are fed under soft rotating brush to make them free from adsorbed particles.

Sorting

• The capsules moving on conveyor are examined visually for sorting defective units by the automated systems or by inspectors .

Printing

• Often capsules are printed before filling operation Printing is done on offer rotary printing machines having capacities of about 7.5 to 8 lakh capsules per hour.

Size of Hard Gelatin Capsules

1. Capsule consists of a base or body and a shorter cap, which fits firmly over its body (base).
2. Empty HGC are made in a variety of sizes.
3. For human use, eight sizes of capsules are available.
4. The capacity of capsule varies from 0.13 ml to 28 ml.
5. For human use, empty capsules ranging in size from 000 (largest) to 5 (smallest) are used.
6. Generally capsules encapsulate ingredients between 65 mg to 1 g.

Shape of Capsules

1. The standard HGC come in traditional, symmetrical bullet or cylindrical shapes.
2. Capsules are either dot sealed or banded to prevent body and cap separation after filling.
3. As an alternative and to achieve other functionalities self-locking capsules are manufactured, for example, coni-snap and snap fit by Park-Davis, Lo-cap as Posilok by Eli Lily and Star-Lok and Lox-It by Scherer.

Filling

1. Capsule filling is a complex process.
2. The HGC can be filled using manual, semi-automatic and automatic capsule filling machines.
3. The choice of capsule size and fill weight depends upon the unit dose requirements and the formulation to be filled.
4. The product to be encapsulated must be well developed to ensure mass uniformity.
5. Filling

1. Manual Filling:
   1. Punch method:
   2. In this method precise number and size of capsule to be filled is selected.
   3. Capsules body and cap is separated. The powder or granules to be filled are taken on a piece of clean paper and filled by holding the capsule body in between thumb and forefinger.
   4. It is a common technique used by pharmacist but is a slow and laborious.
2. Manual Filling:
   1. Volume fill method: This method is based upon the total amount of drug needed based upon the amount per dose per day and total number of dosing days.
   2. Tamping method: This method involves compression of contents. The majority of high speed filling machines does capsule filling using tamping method.
   3. Wax fill method: This method involves traditional steps of melting wax and mixing of the drugs followed by filling the capsules similar to punch method.
3. Machine Filing:
   1. Hand filling of small quantities of capsules is employed for small volume fills for controlled drug substances and to minimize and more readily account for product losses.
   1. For larger quantities up to 3000 capsules/min, automated capsule filling machines are most commonly used.

Read: 17 Important Pharmaceutical excipients in Tablets

Finishing

• On a small scale, capsules are cleaned individually by rubbing them with a clean gauze or cloth.
• On a commercial large scale, capsule-filling machines are affixed with a cleaning vacuum that removes any extraneous material from the capsule surfaces as they exit the equipment.

Manufacturing Defects

1. Major defects include
   1. hard shell formation, cracks, breaks, pinholes or splits,
   1. loss of integrity, colour variation,
   1. non-uniformity of appearance, surface spots and
   1. embedded particles on capsules, non-uniform body and cap, improper fitting,
   1. false odour, empty capsule, foreign matter inside the capsules, improper filling etc.
2. Whereas minor defects are pits, dents, thin area, specks, spots or blemishes, rough surface with adhering spots, improper opacity, etc.

Storage of Hard Gelatin Capsules

1. HGC must be protected against excessive heat and humidity.
2. Recommended storage conditions for empty HGC are 15 to 25 °C and a relative humidity (RH) of 35-65 %.

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