Capsules

Capsules are solid dosage form of medication in which the drug is enclosed in either a hard or soft soluble container or shell made of gelatin. It is also defined as dosage forms in which one or more medicinal or inert substances are enclosed within a small gelatin shell. Most are intended to be swallowed whole, but occasionally the contents may be removed from the gelatin shell and employed as a premeasured medicinal powder.

Advantages of Capsules:

1. Tastelessness
2. Ease of administration
3. Easily filled either extemporaneously or in commercial scale
4. Permit physician to prescribe the exact medication needed by the patient
5. Eliminate the presence of numerous additives, as in the case of tablets which may influence the absorption of the drug and therefore the clinical absorption obtained.
6. Preferred method for administering new therapeutics for evaluation in initial clinical trials.
7. Preference of some patients for capsules.

Two kinds of gelatin capsules.

1. Hard Gelatin Capsules
2. Soft Gelatin Capsules

I. Hard Gelatin Capsules are also known as dry-filled capsule (DFC), which consists of 2 sections, one slipping over the other, completely surrounding the drugs. These are filled by introducing one dose of the formulation into the longer end or base of the capsule and then slipping on the capsule.

A. Preparation of Hard Gelatin Capsules

Preparation of filled hard capsules includes preparing the formulation, selecting the appropriate capsule, filling the capsule shells, and cleaning and polishing the filled capsules. The empty hard capsules are made from gelatin and sugar, colorant and opacifying agent such as titanium dioxide, and 0.15% sulfur dioxide is permitted by the USP to prevent decomposition of gelatin during manufacture.

Gelatin USP is made from the partial hydrolysis of collagen obtained from the skin, white connective tissue, and bones of animals. Type A is obtained by acid processing, while, type B is made by alkali processing.

Capsules shells are molded by dipping cold metallic molds or pins into gelatin solutions sustained at a uniform temperature and an exact degree of fluidity. The variations in gelatin solution viscosity lead to non-uniformity of capsule wall thickness. Once pins have been withdrawn from the gelatin solution, they are rotated while being dried in kilns through which a strong blast of filtered air with controlled humidity is forced. The capsules are mechanically trimmed, stripped and joined.

*Capsule Banding is a very important for manufacturers to make encapsulated products tampered-proof. In certain countries scarcity of drugs resulted in the unethical removal of the contents of capsule and refilled them with an inert material. Then both the refilled and the material which had been removed are resold. To avoid this many capsules are tampered-proof by sealing with a clear, colorless band of gelatin around the capsule joint. Opening the tampered-proof capsule will result to its destruction.

B. Storage Condition

Hard gelatin capsules are stored in a tightly closed glass or plastic containers, protected from dust and extremes of humidity and temperature. These capsules contain 12 - 16% water but water content vary according to the storage conditions. Capsules become brittle in low humidity but are flaccid and lose their shape if stored in high humidity. They do not protect hygroscopic materials from atmospheric water vapor as moisture can diffuse through the gelatin wall. When storage temperature condition is high the quality of the hard gelatin capsules are affected.

C. Sizes

Capsules are available in variable sizes. The hard gelatin capsules, when empty, are numbered from 000, the largest size which can be swallowed, to 5 which is the smallest. Ranges from 600mg to 30mg is approximated capsule capacity for capsules from 000 to 5, respectively. However, the capacity varies because of varying densities of powdered drug materials and degree of pressure used in filling the capsules. Commercially filled capsules are available in the conventional oblong shape except Lilly products, which are known as Pulvules because the products are encapsulated in a bullet shape capsules where the end of the base is tapered.

Approximate Amount of Powder Contained in Capsules

 

D. Selection of Capsules

Generally, hard gelatin capsules are used to encapsulate between 65mg and 1g of powdered material, including the active ingredient and any excipient needed. Experienced pharmacist, often can select the correct size of the capsule needed in a given prescription. A properly filled capsule should have its body filled with the drug mixture and its cap fully extended down the body. The caps is meant to enclose the powder, not to retain additional powder. It is always good to check the weight of each filled capsules.

Aside from choosing the size of capsule, experienced pharmacist is considering the color of the hard gelatin capsules to be used. From the transparent, colorless hard capsule, capsules are also available in various transparent colors such as blue, yellow, pink green, black or reddish-brown. The pink capsule is frequently used by pharmacists for prescription where capsule have been prescribed twice for an individual, or where capsule medication is given to two persons in the same family.

In such cases it is very important to note the color as well as the capsule size on the prescription, so that in case of renewals the refilled prescription will duplicate the original. Manufacturers employ colored capsules to five a specially product a distinctive appearance.

E. Characteristics of a Good Selection of Capsules

1. A diluent, such as lactose, should be added when drug dose for a single capsule is inadequate to fill the capsule.
2. Two or more capsules can be required to provide the particular dose, if the amount of the drug representing a usual dose is too large to place in a single capsule.
3. Lubricants such as magnesium stearate (frequently less than 1%) are added to facilitate the glow of the powder when an automatic capsule filling machine is used.
4. Wetting agents such as lithium carbonate are added to capsule formulations to enhance drug dissolution.

F. Methods of Filling Hard Gelatin Capsules

1. Manual Filling Method or Punch Method
   When a prescription calls for capsules the ingredients are to be mixed by trituration to a fine and uniform powder. Then the mixed powder is transferred on paper and flattened with a spatula in such that the layer of the powder is not greater than about ¹/₃ of the length of the capsule which is being filled. The cap is removed from the selected capsules and held in the left hand, the base is pressed repeatedly against the powder until it is filled. The cap is slipped into the base of the capsule and the whole is weighed. The spatula helps in filling the capsule by pushing the last quantity of the materials into the base.
   Granular material that does not lend itself well to the punch method may be poured into each capsule from the powder parer on which it was weighed. Crystalline materials, especially materials consisting of a mass of filament-like crystals as with the quinine salts, will not fit into a capsule easily unless first powdered. Once filled, capsules must be cleaned and polished. On a small scale, capsules may be cleaned individually or in a small numbers by rubbing them on a clean gauze or cloth. On a large scale, many capsule-filling machines have a cleaning vacuum that removes any extraneous material from the capsules as they leave the machine.
2. Machine Filling Method
   Devices for capsule filling are used such as:

• Hand-Operated Capsule-Filling Machine – this model fills 96 capsules per operation and is made to obtain an hourly production of 1000 capsules. Basic machine is the tray used to hold the fill over the empty capsules, the spreader and roller used to distribute the fill material in the tray and permit it to enter the capsules uniformly, and the packer used to compact the fill in the capsules.
• Capsule-Filling System – capable of filling 2000 capsules per hour. Useful for clinical drug trial lots and small scale production.
• Osaka Automatic Capsule Filler – capable of filling up to 165,000 capsules per hour.

II. Soft Gelatin Capsules are soft, globular, oblong, elliptical, or spherical in shape gelatin shell. Some sugar-coated tablets have only slight difference in appearance to soft gelatin capsules. The soft gelatin capsule has a seam at the point of closure of the two halves, and the contents can be liquid, paste, or powder. The sugar-coated tablets have compressed core but not a seam.

A. Preparation of Soft Gelatin Capsules

Soft Gelatin Capsules are prepared from gelatin shells to which sufficient glycerin or polyhydric alcohol (e.g. sorbitol) has been added to retain permanent flexibility, rendering the shells elastic or plastic-like. These shells are contained with preservatives (e.g. methyl and propyl parabens, sorbic acid) to prevent the growth of fungi. Commercially the shells are available hermetically sealed to prevent the walls from collapsing. One end is elongated so that when it is cut off for filling, sufficient gelatin is provided for the sealing. Soft gelatin capsules provide a convenient and highly acceptable dosage form when the suspending vehicle or solvent is oil.

B. Extemporaneous Preparation of Soft Gelatin Capsules

For extemporaneous filling the empty elastic capsules are made in much the same manner as hard capsules. Cut off the elongated end and inert the liquid with a glass dropper avoiding the soiling of the edges. Then seal the aperture with a hot gelatin solution. If the melted tips do not supply enough sealing solution prepared and additional quantity. Mix Gelatin (10 parts), acacia (1 part), glycerin (10.4 parts) and water (16.7 parts). Heat on a water bath for 12 hours, maintaining the consistency by the addition of water.

C. Uses

Soft gelatin shells may be used to contain liquids, suspension, pasty materials, dry powders, or pelletized materials. Drugs commercially prepared in soft capsules include ethchlorvynol (Placidyl, Abbott), demeclocycline hydrchloride (Declomycin, Lederle), Chlorotrianisene (TACE, Merrell Dow), chloral hydrate (Noctec, Squibb), digoxin (Lanoxicaps, Burroughs Wellcome), vitamin A and vitamin E.

D. Method of Production

For the commercial production of soft gelatin capsules, a number of processes are employed such as:

1. Plate Process – Using a rotary or reciprocating productive die.
2. Celton Capsule Machine Rotary Die Process
3. Norton Capsule Machine
4. Aerogel Capsule Machine

Quality Control

Weight Variation Test

The uniformity of dosage forms can be demonstrated by either weight variation or content uniformity methods. The requirement with respect to variation in the weight of capsule content as provided by the latest official compendia should be consulted for details of these procedures.

Disintegration Test

Usually not required for capsules unless they have been treated to resist solution in gastric fluid (enteric-coated). In this case they must meet the requirement for disintegration of enteric-coated tablets.