Hard and Soft Gelatin Capsule, Advantages, Disadvantages, Excipients, Capsule Filling Machine, Evaluation.

Capsule: hard and soft gelatin capsule.

Capsules are solid unit oral dosage forms of medicament or medicaments enclosed inside empty water-soluble shells. The water-soluble shell is made of gelatine. There are two types of capsule dosage forms. These are hard capsules (hard gelatine capsules) and soft capsules (Soft gelatine capsules).

• Advantages

  • 1. Easy to swallow due to its slippery properties after moistening.

  • 2. Mask taste and odor of medicament.

  • 3. Dose accuracy

  • 4. Medicaments protection from the outside environment

  • 5. Longer shelf life

  • 6. Available in various sizes

  • 7. Attractive appearance

  • 8. Easy to handle, easy to transport easy to carry, easy to store due to its light weight.

  • 9. Easy to manufacture

  • 10. Economical

• Disadvantages

  • 1. Not suitable for hygroscopic medicaments.

  • 2. Not suitable for concentrated preparation that needs to be diluted before administration

HARD CAPSULE:

The Capsule shell of a hard capsule is made of gelatine, a coloring agent, and preservative. Hard gelatine capsules are made of two cylindrical halves that fit together to encapsulate solid or powder medicaments. These two pieces are known as the cap and body. The cylindrical half of a capsule slightly larger in diameter and shorter in length is called a cap. The cylindrical half of the capsule slightly shorter in diameter and longer in length is called the body. Solid or powder of medicament to be encapsulated is filled in the body of the capsule. The cap fits over the body of the capsule to seal the medicament.

A hard gelatine capsule is made of gelatine, water, coloring agents, preservatives, and other additives to improve the stability and strength of the capsule. Empty hard gelatine capsule is available in several sizes. They are numbered from 000 to 5 as per their sizes. The amount of solid or powder encapsulated in any specific capsule depends upon the medicament's density.

• Capsule Number 000, Approx Capacity: 950 mg

• Capsule Number 00, Approx Capacity: 650 mg

• Capsule Number 0, Approx Capacity: 450 mg

• Capsule Number 1, Approx Capacity: 300 mg

• Capsule Number 2, Approx Capacity: 250 mg

• Capsule Number 3, Approx Capacity: 200 mg

• Capsule Number 4, Approx Capacity:150 mg

• Capsule Number 5, Approx Capacity: 100 mg

Excipients (Additives): The following excipients are used in the manufacturing of capsule dosage form.

• 1. Diluents: Diluents are used to increase the bulk of medicaments to be encapsulated. Diluents are used if the dose of the drug is too small. Ex. lactose, mannitol, starch, etc.

• 2. Absorbent: Some medicaments are hygroscopic, deliquescent or eutectic in nature. The hygroscopic or deliquescent powder absorbs moisture from the capsule wall. This makes the capsule wall brittle. This problem can be solved by using absorbent.

Some medicaments tend to liquefy upon their mixing. They are called eutectic powder. These medicaments are mixed with absorbent separately and then encapsulated in a capsule. Examples of absorbents are magnesium oxide, magnesium carbonate, calcium oxide, calcium carbonate, kaolin, etc.

• 3. Glidants: Glidants ensure the free flow of medicament powder inside the capsule filling machine. Examples are magnesium stearate, calcium stearate, etc.

• 4. Antidusting compound: They are added in formulation to stop powder medicaments dust formation during capsule filling. Example: edible oil.

Hard gelatine capsule filling machine:

It is used to fill various types of medicaments such as powder, pellet, granules, or liquid into hard gelatine capsules. Hand-operated hard gelatine capsule filling machine consists of

• 1. A loading tray with 200 to 300 holes to hold empty gelatine capsules. It has one cap plate to hold the capsule's cap and one base plate to hold the capsule body.

• 2. A powder tray,

• 3. A pin plate with 200 to 300 pins,

• 4. A sealing plate fitted with a rubber top.

• 5. A lever and a cam handle. A brush to clean excess powder.

All parts of the machine are made of stainless steel. It can be easily dismantled for cleaning of machine and reassembled for filling of empty capsule.

Working: Fill empty hard gelatine capsules into holes in the loading tray and place them over the bed of the machine. Operate a cam handle to lock the body of the empty gelatine capsule and to separate the body from the cap of the empty gelatine capsule. Separate the cap from the body by operating the lever of the machine. Place the powder tray properly. Fill the accurately weighed mixture of medicaments and additives powder over the powder tray. Spread powder by using a scraper to fill powder into the body of the capsule. Lower down the pin plate to press powder into the body of the capsule. Remove the powder tray and place the cap holding tray. It is called a sealing plate. Press sealing plate with rubber top. Operate a lever to unlock the body and cap of the capsule. Remove the loading tray and collect the filled capsule.

• Cleaning of capsule: After filling of capsule requires to removal of dust present on the capsule. It is carried out by using a soft cloth.

• Capsule sealing: Ensure all capsules are sealed properly to stop powder leakage from the capsule. During handling there may be unsealed capsules.

Difficulties in filling hard gelatine capsules

• 1. Hygroscopic and deliquescent powder: Hygroscopic substances absorb moisture or water vapor from surroundings. Deliquescent substances liquefy after absorbing moisture or water vapor from surroundings. These substances inside the capsule absorb moisture or water vapor from the capsule wall. This makes the capsule shell brittle. It can be solved by adding absorbent as an additive with medicaments before it fills into the capsule shell. These capsules should be stored in an airtight glass vial.

• 2. Eutectic mixture: Two or more substances liquefy after their mixing to form an eutectic mixture. These substances are mixed with absorbent separately and then filled into a capsule shell.

• 3. Potent powder: Potent drugs have strong pharmacological effects. They produce action in very low doses such as 50mg or less. It is difficult to fill these drugs into capsules accurately due to low doses. These drugs are mixed with diluents or bulking agent to increase their volume and weight before filling into gelatine capsule shell/

• 4. Granular medicaments: It is difficult to fill granular drugs into capsule shells. They are not compressible inside the capsule shell. They flow out from the capsule shell during compression. It can be solved by mixing alcohol with moist granules.

• 5. Liquids: Liquid that dissolves gelatine cannot be filled into a capsule shell. Oils or any liquid that cannot dissolve gelatine can be filled into a capsule shell. If their quantity is small then they can be mixed with absorbent before their filling into the capsule.

• 6. Incompatible medicaments: Incompatible drugs are not filled in one capsule. One drug is filled in a small capsule. This small capsule and other drugs are filled in larger capsule sizes.

SOFT GELATINE CAPSULE

Soft gelatine capsule encloses liquid or semisolid medicaments. The soft gelatine capsule shell is soft and elastic and made of gelatine with a plasticizer such as glycerine, sorbitol, or propylene glycol. Plasticizer makes soft gelatine capsules flexible. It also contains preservatives to prevent the growth of fungus and bacteria. Soft gelatine capsule is available in various shapes such as cylindrical, tube, and oval. Normally 0.1 ml to 30 ml of medicament can be filled in one gelatine capsule shell. Oil such as liver oil, vitamin A, vitamin D, suspension, food concentrate, ophthalmic preparations, etc are dispensed as soft gelatine capsules.

Preparation of soft gelatine capsules

Manufacturing of soft gelatine shell and filling of medicaments into soft gelatine shell is carried out simultaneously. A rotary die machine is used for this purpose. It consists of two hoppers and two rotator dies. One hopper has liquid gelatine mixture and the other hopper has liquid medicament. Rotator dies rotates in opposite direction to each other at the same speed.

The gelatine liquid mixture comes out from the hopper as two ribbons (Continuous sheet) of gelatine. These continuous sheets of gelatine come over both rotating dies and enter in between both dies. At this stage measured amount of medicament is pumped to be enclosed inside both continuous sheets of gelatine. Heat and pressure from both rotating dies to seal the ribbon and cut them to form a soft gelatine capsule. The capsule formed is passed through the bathing step to remove lubricants from the external shell of the soft gelatine capsule.

EVALUATION OF CAPSULE or STANDARDISATION OF CAPSULES:

Capsules are evaluated on the following parameters

• 1. Appearance: Inspect capsules visually to detect defects or abnormalities like cracks, discoloration, etc.

• 2. Weight variation: There should be uniformity in the weight of capsules. Weigh 20 capsules and determine the average weight of the capsule. Then weigh each capsule individually. Decide weight variation. It should be in between 90% to 110%.

• 3. Content uniformity: Capsules must pass the uniformity test as per the monograph in the pharmacopeia.

• 4. Disintegration: The disintegration test apparatus for the tablet is used to check the disintegration of the capsule. The disintegration test apparatus has six tubes. Add one capsule to each tube. Suspend these tubes in a basket carrying water at 370C ±20C. Switch on the apparatus and operate it. A hard gelatine capsule passes the test if no residue is present in the tube at the end of 60 minutes. A soft gelatine capsule passes the test if no residue is present in the tube at the end of 30 minutes.

• 5. If any one or two capsule fails to pass the test then repeat it using 12 capsules. Not less than 16 tablets should pass the test from 16 tablets (6 in the first test and 12 in the second test).

• 6. Dissolution test: The dissolution test apparatus for the tablet is used to check the dissolution of the capsule. Pace the specified number of capsules in the dry basket. Place 1000 ml of distilled water or dissolution medium specified in the monograph of the capsule in the dissolution test apparatus vessel. Maintain its temperature at 37 degrees C ±20C. The deep basket containing the capsule in a dissolution medium. Rotate the basket at the speed mentioned in the monograph of the capsule. Withdraw samples from the vessel at the time interval mentioned in its monograph. Determine the active constituent amount in the sample by using the assay method mentioned in the monograph. The sample passes the test if the medicament amount is not less than 70% of the amount mentioned in the monograph.

Packaging and storage of capsules

• Preferably capsule should be packed in a well-closed glass container or plastic container.

• It should be stored in a dry place at a temperature of around 30 degrees C.

• Capsules can also be packed in strip or blister packing.

• Capsules stored in glass containers are more stable than in strip or blister packing.

• But it is true till the glass container is not opened. It will be reversed after the opening of the glass container.

Cotton is placed inside the vial to protect the capsule during its transportation. Silica gel or anhydrous calcium chloride packet is placed inside the vial to protect the capsule from moisture.

Alok Bains