Different Capsule Dosage Forms
Pharmaceutical and nutraceutical products are increasingly being administered in the form of capsules. These have many advantages over tablets which, until recently, have been the more widely adopted dosage form. Empty capsules are now available in variety of shapes, sizes and materials, each capsule generally containing a single dose of active ingredient. As with tablets, certain other encapsulation excipients may be incorporated in the material that is loaded into a capsule. These include inert diluents, lubricants and glidants, wetting agents and disintegrants. The capsule shell may also incorporate antimicrobial preservatives, fillers, flavouring agents, sweeteners and coloring agents. It may also be coated with a film of material designed to alter the release of the API. Branding and dosage information may be printed on the outer surface of the capsule.
There are essentially two forms of capsule used for pharmaceutical and nutraceutical products – hard capsules and soft capsules. Traditional capsules are made from gelatin, which is a widely produced animal-based product. More recently HPMC (hydroxyprolymethyl cellulose) and Pullulan have become a successful alternatives and are available commercially for both pharmaceutical and nutraceutical products.
Hard capsules are normally employed for dry solid active ingredients. The capsules are manufactured in two halves – a body and cap – to assist with filling. Gelatin has been the material of choice for capsules because of the ability of a solution to gel and form a solid at a temperature just above room temperature. Traditional gelatin capsules are therefore formed by dipping finger-shaped pin forms at room temperature into hot gelatin solution and then extracting them and allowing the resulting surface film of gelatin to dry out on the pins through a series of controlled air drying kilns. Once the film dries out, the capsules are stripped from the pins by bronze jaws and trimmed to length by stationary knives while the capsules are being spun in chucks or collets. After being trimmed to the exact length, the cap and body sections are ejected from the machine. Manufacturers supply the unlocked body and cap of each capsule ready to be filled with the appropriate drug or nutraceutical ingredients.
More than one type of drug can be encased in a pharmaceutical capsule. Indeed it is quite common for the drugs to be in different forms, e.g., one as a tablet and one as a smaller capsule or powder. Both drug types can be encased in a larger capsule.
The types of materials that can be loaded into empty capsules include:
- Dry solids – powders, granules, pellets or small tablets
- Semi-solids – suspensions or pastes
- Liquids – non aqueous liquids such as alcohols or oils
Soft Gelatin Capsule
Soft gelatin capsules, also called soft gels, are thicker than hard gelatin capsules, and require special manufacturing equipment, either a rotary capsule machine or a dosator machine that uses the principle of drop formation to create the capsules. A rotary capsule machine can continuously manufacture the capsules and insert the fill. Typical production rates are between 25000 and 30000 capsules per hour.
The gelatin in soft capsules usually contains 20-30% by weight of a plasticizer such as glycerine, sorbitol or ethylene glycol. The amount and choice of the plasticizer contribute to the hardness of the final product and may even affect its dissolution or disintegration characteristics, as well as its physical and chemical stability. The composition of the plasticizer is chosen to minimise any interaction or migration between the fill and the soft gel shell. A preservative, such as beta-naphthol, may be added to inhibit bacterial growth on the gelatin. Colouring agents and opacifiers may also be added as well as sweetening agents. The thickness of the gelatin depends on the material to be encased within the capsule and the temperature and humidity of the surroundings. Soft gels generally contain 30-40% water of the wet formulation, necessary to ensure proper processing during gel preparation and soft gel encapsulation. After the capsule is filled, the gelatin is progressively dried so that the final capsule may contain between 6% and 13% by weight of water.
Soft gel capsules are available in a variety of shapes and sizes e.g.,
- Cylindrical – 0.15 – 25 ml
- Ovoid – 0.05 – 7 ml
- Pear shaped – 0.3 – 5 ml
- Spherical - 0.05 – 5 ml
- Tubes – 0.3 – 5 ml
There are three types of fill materials that can be used with soft gel capsules:
- Neat substances, especially oils, e.g. cod liver oil
- Solutions – active materials dissolved in a carrier such as a oil (e.g., soybean), polyethylene glycol, or a solvent that does not degrade the gelatine shell (e.g., dimethyl isosorbined and diethylene glycol).
- Suspension or paste – material up to about 30% solids can be accommodated before viscosity and filling become a problem.
A small amount of water or alcohol (up to 10% by volume) may be added to the fill if needed to assist solubility of ingredient(s). Glycerin can also be added to retard any migration of plasticizer out of the gelatine shell into the fill. Up to 10% by weight of polyvinylpyrrolidone may also be added in combination with polyethylene glycol to improve stability of the fill.
Many materials cannot be encapsulated in soft gels owing to their solubility in water and thus their ability to affect the gelatine shell. Also substances that are unstable in the presence of moisture (e.g., aspirin) will not show sufficient chemical stability in soft gel capsules.
Modified Release Capsule
Both hard or soft gel capsules can be chemically modified to alter the release of the active ingredient(s). If the drug is water-soluble and in a hard capsule and a fast release is desired, the excipients should be hydrophilic and neutral whereas for slow release of water soluble drugs the excipients will slow the release. Rapid release from capsules can also be obtained by piercing the outer film with small holes or incorporating a small quantity of citric acid and sodium bicarbonate to assist in opening the capsule by evolution of carbon dioxide.
A small concentration (up to 1%) of sodium lauryl sulfate may be added to the gel of a soft capsule to enhance penetration of water and speed dissolution. If slow release from a soft capsule is required, polymer or alginates may be added.
Enteric capsules are another form of modified release capsule, and again they maybe in the hard or soft form. The encapsulating material is designed to resist the stomach acid until it reaches the intestinal fluid where at a higher pH it breaks down and releases the active ingredients. Coatings that have been employed for enteric capsules include cellulose acetate phthalate, and mixtures of waxes and fatty acids and/or their esters. These function by being insoluble in acid but soluble in alkali. Some modern coating materials have also been found to erode over time on exposure to gastrointestinal fluids, rather than as a function of pH by itself. Application of such coatings requires considerable skill and additional equipment, and should probably only be used for medications that are not be of a critical nature.