Gelatin is extensively used in various pharmaceutical formulations, including as a biodegradable matrix material in implantable delivery systems. However, its most common application is in the production of hard or soft gelatin capsules.
Gelatin capsules are unit-dosage forms primarily intended for oral administration. Soft capsules are also available for rectal and vaginal use. Hard capsules can be filled with solids (such as powders, granules, pellets, tablets, and their mixtures), as well as semisolid and liquid fillings. In contrast, soft capsules are mainly filled with semisolid or liquid substances. In hard capsules, the active drug is always part of the filling, whereas in soft capsules, the drug can also be incorporated into the thick capsule shell.
Gelatin dissolves in warm water (above 30°C), causing the capsule to swell and eventually dissolve in gastric fluid, releasing its contents rapidly.
Hard capsules are produced in two parts by dipping lubricated stainless steel mold pins into a gelatin solution heated to 45 to 55°C. The viscosity of the solution, which varies based on the capsule size and whether the cap or body is being formed, determines the film thickness. The gelatin adheres to the pins through gelation, and the resulting film thickness is controlled by the solution’s viscosity. The capsule shells are then passed through a stream of cool air to set the gelatin, followed by slow drying with large volumes of humidity-controlled air heated slightly above ambient temperature, blown directly over the pins. The capsule halves are then removed from the pins, trimmed, and assembled.
Gelatin used for hard capsules may include various coloring agents and antimicrobial preservatives. Small quantities of surfactants may also be present in the shells as residues from the pin lubricant. However, the use of preservatives is now discouraged in accordance with current GMP principles. Capsule shells can be treated with formaldehyde to make them insoluble in gastric fluid. Standard capsules range in volume from 0.13 to 1.37 mL. For veterinary use, capsules with volumes between 3 and 28 mL are available, and capsules with a capacity of 0.025 mL are available for toxicity studies in rats.
Unlike two-piece hard capsules, soft gelatin capsules are manufactured, filled, and sealed in a single process. The gelatin used for soft shells has a lower gel strength and viscosity compared to that used for hard capsules, resulting in more flexible shells. Soft shell formulations include plasticizers such as polyalcohols (glycerin, propylene glycol, polyethylene glycol). Sorbitol can be added as a moisturizing agent, with the additional water acting as a plasticizer. Coloring and opacifying agents are also incorporated.
The filling can chemically interact with the gelatin and plasticizer, potentially causing migration of filling components into the shell and vice versa. These interactions must be considered during the formulation of both the gelatin shell and the filling. The primary method for producing soft gelatin capsules is the rotary die method (RP Scherer), while the Globex system (Industrial Technologic Solutions Ltd) is an alternative for small volumes of round capsules. Soflet Gelcaps (Banner Pharmacaps) are tablets coated with a gelatin film.
Gelatin is also utilized for the microencapsulation of drugs, where the active drug is enclosed within a microsized capsule or beadlet, allowing it to be handled as a powder. The first microencapsulated drugs were fish oils and oily vitamins in gelatin beadlets prepared by coacervation.
Low-molecular-weight gelatin has been studied for its ability to enhance the dissolution of orally ingested drugs. Ibuprofen–gelatin micropellets have been developed for the controlled release of the drug. Other applications of gelatin include the preparation of pastes, pastilles, pessaries, and suppositories. Additionally, it serves as a tablet binder and coating agent, as well as a viscosity-increasing agent for solutions and semisolids.
Therapeutically, gelatin has been used in wound dressings and as a plasma substitute, although anaphylactoid reactions have been reported in the latter use. Absorbable gelatin is available in various forms, including sterile film, ophthalmic film, sterile sponge, sterile compressed sponge, and sterile powder from sponge. Gelatin sponge possesses hemostatic properties.
Gelatin is also widely used in food products and photographic emulsions.