Gelatin

Absorption

The bioavailability of gelatin was indirectly studied by the determining the bioavailability of total hydroxyproline in gelatin using a pharmacokinetic method after oral ingestion in rats.
The relative and absolute bioavailability of gelatin were 74.12% and 85.97%, respectively. The amino acid profile of plasma showed that 41.91% of the digested gelatin was absorbed from the intestine in the peptide form, and there was a linear correlation between the absorbed amount of an amino acid and its content in gelatin (R(2) = 0.9566). Furthermore, 17 types of collagen peptide were purified by multi-step chromatography and identified with ultra-performance liquid chromatography-electrospray ionisation-mass spectrometry .

Toxicity

LD50 Rat >3750 mg/kg .
Gelatin solutions have shown to increase the risk of anaphylaxis and may be harmful by increasing mortality, renal failure, and bleeding likely due to extravascular uptake and impairment of coagulation. .
Gelatin can cause an unpleasant taste, a sensation of abdominal heaviness, bloating, heartburn, as well as belching .
Using gelatin as a plasma expander appears to have no significant advantages over crystalloids or isotonic albumin on mortality and may have a slightly higher risk of requiring allogeneic blood transfusion in perioperative and critically ill patients.
A meta-analysis found that using gelatin as a volume expander in vivo has no significant advantages over currently used volume expanders such as isotonic albumin or crystalloids and may slightly increase the risk of requiring a blood transfusion .

Description

Gelatin does not occur in nature as such, but is derived by hydrolysis of collagen, the chief protein component in connective tissues of the animal body. Extraction of gelatin for use as a glue by cooking hides dates back to the earliest recorded history of man and appears in the literature of the items up to the present day. During the early years of the Napoleonic era it was manufactured on a large scale in an attempt to alleviate the food shortages resulting from the English naval blockade of Europe. Gelatin was first manufactured in the U.S. in 1809. In 1845 a U.S. patent was granted for a gelatin which contained all the ingredients fitting it for table use, and required only the addition of hot water and subsequent cooling to prepare it for serving.
Quantitatively, collagen is concentrated in the skin, the bone of the skeletal system and the tendons attaching muscles to the skeleton, although it occurs throughout all of the tissues and organs to a lesser degree. Chemically, collagen and gelatin are virtually indistinguishable, but the process of collagen extraction results in converting the fibrous, water-insoluble, highly organized macromolecules (tropocollagens) irreversibly into gelatin which has dissimilar physical characteristics. Variations in gelatin properties due to source and treatment make it a highly diverse, heterogeneous substance, particularly with regard to molecular weight.
The major sources of collagen are cattle hides, pig skins and bones. The resulting gelatin is of two types commonly designated A and B, depending upon which of two processes are used to convert the collagen into gelatin. Type A gelatin is derived primarily from pig skin by acid processing; it has an isoelectric point between pH 7 and pH 9. Type B is from cattle hides and bones by alkaline or lime processing and has an isoelectric point between pH 4.7 and pH 5.1. Gelatin from different sources and as prepared by the different processes exhibits small differences in amino acid composition as shown in the following table. The nutritionally essential amino acid, tryptophan, is absent in gelatin. Gelatin also is unusual in that it contains large proportions of glycine, proline and hydroxyproline, and a small percentage of hydroxylysine, an amino acid rare in proteins. (SCOGS, 1975).
The major use of gelatin in the U.S. is in food products, principally in gelatin desserts, meat products, consommes, marshmallows, candies, bakery and dairy products and ice cream. A substantial portion of each year’s production (imported and domestic) is also used in the pharmaceutical, photographic and paper industries. (SCOGS, 1975).
Gelatin is colorless or slightly yellow, transparent, brittle, practically odorless, tasteless, presenting as sheets, flakes or a coarse powder. On being warmed, gelatin disperses into the water resulting in a stable suspension. Water solutions of gelatin will form a reversible gel if cooled below the specific gel point of gelatin. The gel point is dependent on the source of the raw material. Gelatin extracted from the tissues of warm-blooded animals will have a gel point in the range of 30°C - 35°C. Gelatin extracted from the skin of cold-water ocean fish will have a gel point in the range of 5°C - 10°C. Gelatin is soluble in aqueous solutions of polyhydric alcohols such as glycerin and propylene glycol.

Chemical properties

white to slightly yellow powder, also knownas glutin,is a protein found in many animal tissues including skin, cartilage, horn, and bone. Gelatin is used in leather dressings, in photography, in metallurgy, in the plastics industry, and in pharmaceuticals.

Physical properties

Gelatin is colorless or slightly yellow, transparent, brittle, practically odorless, tasteless, presenting as sheets, flakes or a coarse powder. On being warmed, gelatin disperses into the water resulting in a stable suspension. Water solutions of gelatin will form a reversible gel if cooled below the specific gel point of gelatin. The gel point is dependent on the source of the raw material. Gelatin extracted from the tissues of warm-blooded animals will have a gel point in the range of 30°C - 35°C. Gelatin extracted from the skin of cold-water ocean fish will have a gel point in the range of 5°C - 10°C. Gelatin is soluble in aqueous solutions of polyhydric alcohols such as glycerin and propylene glycol.

Occurrence

Gelatin is a protein obtained by partial hydrolysis of collagen, the chief protein component in skin, bones, hides, and white connective tissues of the animal body. Type A gelatin is produced by acid processing of collagenous raw material; type B is produced by alkaline or lime processing. Because it is obtained from collagen by a controlled partial hydrolysis and does not exist in nature, gelatin is classified as a derived protein. Animal glue and gelatin hydrolysate, sometimes referred to as liquid protein, are products obtained by a more complete hydrolysis of collagen and can thus be considered as containing lower molecular-weight fractions of gelatin.

History

Extraction of gelatin for use as a glue by cooking hides dates back to the earliest recorded history of man and appears in the literature of the items up to the present day. During the early years of the Napoleonic era it was manufactured on a large scale in an attempt to alleviate the food shortages resulting from the English naval blockade of Europe. Gelatin was first manufactured in the U.S. in 1809. In 1845 a U.S. patent was granted for a gelatin which contained all the ingredients fitting it for table use, and required only the addition of hot water and subsequent cooling to prepare it for serving.

The Uses of Gelatin

As stabilizer, thickener and texturizer in food; manufacture of rubber substitutes, adhesives, cements, lithographic and printing inks, plastic Compounds, artificial silk, photographic plates and films, matches, light filters for mercury lamps; clarifying agent; in hectographic masters; sizing paper and textiles; for inhibiting crystallization in bacteriology, for preparing cultures. Pharmaceutic aid (suspending agent; encapsulating agent; tablet binder; tablet and coating agent). Gelatin is a hydrophilic chemical useful in histochemistry, bacterial culture media and light microscope autoradiography.

The Uses of Gelatin

gelatin is used as a natural sealant against moisture loss and as a formulation thickener. The films produced by gelatin are tacky when moist and hard, and brittle when dry. It is obtained by the partial hydrolysis of mature collagen derived from the skin, connective tissue, and bones of animals. It does not have the waterbinding ability of soluble collagen.

The Uses of Gelatin

Gelatin is a protein that functions as a gelling agent. it is obtained from collagen derived from beef bones and calf skin (type b) or pork skin (type a). type b is derived from alkali-treated tissue and has an isoelectric point between ph 4.7 and 5.0. type a is derived from acid-treated tissue and has an isoelectric point between ph 7.0 and 9.0. it forms thermally reversible gels which set at 20°c and melt at 30°c. the gel strength is measured by means of a bloom gellometer and ranges from 50 to 300 with a 250 bloom being the most common. it is used in desserts at 8–10% of the dry weight, in yogurt at 0.3–0.5%, in ham coatings at 2–3%, and in confectionery and capsules at 1.5–2.5%.

Indications

Gelatin is used for weight loss and for treating osteoarthritis, rheumatoid arthritis, and brittle bones (osteoporosis). Some people also use it for strengthening bones, joints, and fingernails. Gelatin is also used for improving hair condition and to shorten the recovery after exercise and sports-related injury . Gelatin is used in preparations of foods, cosmetics, and medicine .
Plasma volume expander in hypovolaemic shock . Haemostatic .
Gelatin-based hydrogels are being used in drug delivery and tissue engineering because they are able to promote cell adhesion and proliferation. In addition, these hydrogels can be used as wound dressings because of their attractive fluid absorbance properties. Manufacturing technologies such as ultraviolet stereolithography and two-photon polymerization can be used to prepare structures containing photosensitive gelatin-based hydrogels .

Background

Gelatin is a multifunctional ingredient that is used in foods, pharmaceuticals, cosmetics, and photographic films as a gelling agent, stabilizer, thickener, emulsifier, as well as film former.
As a thermoreversible hydrocolloid with a small gap between its melting and gelling temperatures, gelatin provides unique advantages over carbohydrate-based gelling agents. Gelatin is mainly produced from porcine skin, and cattle hides and bones.
Some alternative raw substances have recently garnered attention from both researchers and the industry not only because they overcome religious concerns shared by both Jews and Muslims but also because they may provide scientific advantages over gelatins from mammal origins.
Fish skins from a number of fish species a type of substance that has been comprehensively studied as a source for gelatin production. Fish skins have a significant potential for the production of high-quality gelatin with different melting and gelling temperatures over a much larger range than mammalian gelatins but have a sufficiently high level of gel strength and viscosity.
Interestingly, horse gelatin has been studied and it was found that in the horse, gelatin influences the homeostasis of the amino acids required for cartilage synthesis . An increasing number of novel applications have been found for collagen and gelatin.
Gelatin is generally recognized as safe (GRAS) by the FDA to be a non-hazardous food or food ingredient. The FDA withdrew its approval for the use of all intravenous drug products containing gelatin. Gelatin continues to be approved for other routes of administration.

What are the applications of Application

Gelatin is a hydrophilic chemical useful in histochemistry, bacterial culture media and light microscope autoradiography

Production Methods

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°C 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°C) 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°C 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°C. 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.

Definition

A pale yellow protein obtained from the bones, hides, and skins of animals, which forms a colloidal jelly when dissolved in hot water. It is used in jellies and other foods, to make capsules for various medicinal drugs, as an adhesive and sizing medium, and in photographic emulsions.

General Description

Gelatin, NF, is a protein obtained by the partial hydrolysis of collagen, an albuminoid found in bones, skin, tendons, cartilage, hoofs, and other animal tissues. Gelatin is used in the preparation of capsules, in the coating of tablets, and, with glycerin, as a vehicle for suppositories. It has also been used as a vehicle when slow absorption is desired for drugs.

Agricultural Uses

Gelatin is a colorless or pale yellow water-soluble protein obtained by boiling collagen with water and evaporating the water. It is an ingredient in jellies and baked goods. It is also used to make medicinal capsules, and coat photographic films.

Pharmaceutical 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. Hard capsules can be filled with solid (powders, granules, pellets, tablets, and mixtures thereof), semisolid and liquid fillings, whereas soft capsules are mainly filled with semisolid or liquid fillings. In hard capsules, the active drug is always incorporated into the filling, while in soft capsules the drug substance can also be incorporated into the thick soft capsule shell. Gelatin is soluble in warm water (>30°C), and a gelatin capsule will initially swell and finally dissolve in gastric fluid to release its contents rapidly.
Gelatin is also used for the microencapsulation of drugs, where the active drug is sealed inside a microsized capsule or beadlet, which may then be handled as a powder. The first microencapsulated drugs (beadlets) were fish oils and oily vitamins in gelatin beadlets prepared by coacervation.
Low-molecular-weight gelatin has been investigated for its ability to enhance the dissolution of orally ingested drugs. Ibuprofen–gelatin micropellets have been prepared for the controlled release of the drug. Other uses of gelatin include the preparation of pastes, pastilles, pessaries, and suppositories. In addition, it is used as a tablet binder and coating agent, and as a viscosity-increasing agent for solutions and semisolids.
Therapeutically, gelatin has been used in the preparation of wound dressings and has been used as a plasma substitute, although anaphylactoid reactions have been reported in the latter application. Absorbable gelatin is available as sterile film, ophthalmic film, sterile sponge, sterile compressed sponge, and sterile powder from sponge. Gelatin sponge has hemostatic properties.
Gelatin is also widely used in food products and photographic emulsions.

Biochem/physiol Actions

Gelatin from fish skin can be used in the preparation of various gels based on their gelling characteristics. It can also be used as an additive in surimi processing to enhance the functional and mechanical properties of gel.

Pharmacokinetics

Gelatin contains collagen, which is one of the materials that make up cartilage and bone .
In addition to their well-established value as a nutritional protein source, collagen and collagen-derived products may exhibit various potential biological activities on cells and the extracellular matrix through the corresponding food-derived peptides post-ingestion. This could justify their applications in dietary supplements and pharmaceutical agents .
Gelatin is a protein that is used as a hemostatic in surgical procedures. It is also used as a plasma volume expander in hypovolemic shock. Gelatin rods structures may also be used to temporarily block tear outflow in cases of dry eye .

Safety Profile

An experimental teratogen. Experimental reproductive effects. When heated to decomposition it emits acrid smoke and irritating fumes.

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

Metabolism

Not Available

storage

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°C, 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°C, and gel strength may be reduced by half when a solution is heated at 80°C 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.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.(4) At temperatures above about 50°C, 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°C, and gel strength may be reduced by half when a solution is heated at 80°C 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.

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.

Regulatory Status

GRAS listed. Included in the FDA Inactive Ingredients Database (dental preparations; inhalations; injections; oral capsules, pastilles, solutions, syrups and tablets; topical and vaginal preparations). Included in medicines licensed in the UK, Europe, and Japan. Included in the Canadian List of Acceptable Non-medicinal Ingredients.