Gelatin

Category

Coating Agents; Film-forming Agents; Gelling Agents; Suspending Agents; Tablet Binder; Viscosity-increasing Agents

Grade

Pharmceutical Excipients

Description

Gelatin occurs as a light-amber to faintly yellow-colored, vitreous, brittle solid. It is practically odorless and tasteless, and is available as translucent sheets, flakes, and granules, or as a coarse powder.

UNII

2G86QN327L

Chemical Name

Gelatin

CAS Number

9000-70-8

Synonyms

Byco; Cryogel; E441; gelatina; gelatine; Instagel; Kolatin; Solugel; Vitagel

Administration route

Dental; inhalations; injections; oral; topical and vaginal

Dosage Form

Dental preparations; inhalations; injections; oral capsules, pastilles, solutions, syrups and tablets; topical and vaginal preparations

Stability and Storage Conditions

Dry gelatin is stable in air. Aqueous gelatin solutions are also stable for long periods if stored under cool conditions but they are subject to bacterial degradation. At temperatures above about 50℃, aqueous gelatin solutions may undergo slow depolymerization and a reduction in gel strength may occur on resetting. Depolymerization becomes more rapid at temperatures above 65℃, and gel strength may be reduced by half when a solution is heated at 80℃ for 1 hour. The rate and extent of depolymerization depends on the molecular weight of the gelatin, with a lower-molecular-weight material decomposing more rapidly.Gelatin may be sterilized by dry heat. The bulk material should be stored in an airtight container in a cool, well-ventilated and dry place.

Source and Preparation

Gelatin is extracted from animal tissues rich in collagen such as skin, sinews, and bone. Although it is possible to extract gelatin from these materials using boiling water, it is more practical to first pretreat the animal tissues with either acid or alkali. Gelatin obtained from the acid process is called type A, whereas gelatin obtained from the alkali process is called type B. The acid-conditioning process (manufacture of type A gelatin) is restricted to soft bone ossein (demineralized bones), sinew, pigskin, calfskin and fish skins for reasons of gaining sufficient yield. The material is cut in pieces and washed in cold water for a few hours to remove superficial fat. It is then treated with mineral acid solutions, mainly HCl or H2SO4, at pH 1-3 and 15-20℃ until maximum swelling has occurred. This process takes approximately 24 hours. The swollen stock is then washed with water to remove excess acid, and the pH is adjusted to pH 3.5-4.0 (pigskin, fish skin) or 2.0-3.5 (all other tissues) for the conversion to gelatin by hot-water extraction. The hydrolytic extraction is carried out in a batch-type operation using successive portions of hot water at progressively higher temperatures (50-75℃) until the maximum yield of gelatin is obtained. The gelatin solution is then filtered through previously sterilized cellulose pads, deionized, concentrated to about 20-25% w/v and sterilized by flashing it to 138℃ for 4 seconds. The dry gelatin is then formed by chilling the solution to form a gel, which is air-dried in temperature-controlled ovens. The dried gelatin is ground to the desired particle size. In the alkali process (liming), demineralized bones (ossein) or cattle skins are usually used. The animal tissue is held in a calcium hydroxide (2-5% lime) slurry for a period of 2-4 months at 14-18℃. At the end of the liming, the stock is washed with cold water for about 24 hours to remove as much of the lime as possible. The stock solution is then neutralized with acid (HCl, H2SO4, H3PO4) and the gelatin is extracted with water in an identical manner to that in the acid process, except that the pH is kept at values between 5.0-6.5 (neutral extraction). During the preparation of the bovine bones used in the production of gelatin, specified risk materials that could contain transmissible spongiform encephalopathies (TSEs) vectors are removed. TSE infectivity is not present in pharmaceutical grade gelatin.

Applications

Gelatin is widely used in a variety of pharmaceutical formulations, including its use as a biodegradable matrix material in an implantable delivery system, although it is most frequently used to form either hard or soft gelatin capsules.Gelatin capsules are unit-dosage forms designed mainly for oral administration. Soft capsules on the market also include those for rectal and vaginal administration.

Safety

Gelatin is widely used in a variety of pharmaceutical formulations, including oral and parenteral products.In general, when used in oral formulations gelatin may be regarded as a nontoxic and nonirritant material. However, there have been rare reports of gelatin capsules adhering to the esophageal lining, which may cause local irritation. Hypersensitivity reactions, including serious anaphylactoid reactions, have been reported following the use of gelatin in parenteral products.There have been concerns over the potential spread of BSE/TSE infections through bovine derived products. However, the risk of such contamination of medicines is extremely low. LD50 (rat, oral): 5 g/kg TDLo (mouse, IP): 700 mg/kg

Incompatibilities

Gelatin is an amphoteric material and will react with both acids and bases. It is also a protein and thus exhibits chemical properties characteristic of such materials; for example, gelatin may be hydrolyzed by most proteolytic systems to yield its amino acid components. Gelatin will also react with aldehydes and aldehydic sugars, anionic and cationic polymers, electrolytes, metal ions, plasticizers, preservatives, strong oxidizers, and surfactants. It is precipitated by alcohols, chloroform, ether, mercury salts, and tannic acid. Gels can be liquefied by bacteria unless preserved.Some of these interactions are exploited to favorably alter the physical properties of gelatin: for example, gelatin is mixed with a plasticizer, such as glycerin, to produce soft gelatin capsules and suppositories; gelatin is treated with formaldehyde to produce gastroresistance.