Definition
ChEBI: A triglyceride obtained by acetylation of the three hydroxy groups of glycerol. It has fungistatic properties (based on release of acetic acid) and has been used in the topical treatment of minor dermatophyte infections.
Description
§ 184.1901(a) Triacetin (C8H14O6) (102-76-1), also known as 1,2,3-propanetriol
triacetate or glyceryl triacetate, is the triester of glycerin and acetic
acid. Triacetin can be prepared by heating glycerin with acetic
anhydride alone or in the presence of finely divided potassium
hydrogen sulfate. It can also be prepared by the reaction of oxygen
with a liquid-phase mixture of allyl acetate and acetic acid using
a bromide salt as a catalyst.
Originator
Enzactin,Ayerst,US,1957
Occurrence
Reported found in papaya.
Preparation
By direct reaction of glycerol with acetic acid in the presence of Twitchell’s reagent, or in benzene solution of glycerol and
boiling acetic acid in the presence of a cationic resin (Zeo-Karb H) pretreated with dilute H2SO4.
Production Methods
Triacetin is prepared by the esterification of glycerin with acetic
anhydride.
Manufacturing Process
200 grams of allyl acetate, 450 grams of glacial acetic acid and 3.71 grams of
cobaltous bromide were charged to the reactor and the mixture was heated to
100°C. Pure oxygen was then introduced into the reactor below the surface of
the liquid reaction mixture at the rate of 0.5 standard cubic feet per hour.
Initially, all of the oxygen was consumed, but after a period of time oxygen
introduced into the mixture passed through unchanged. During the course of
the reaction, a small quantity of gaseous hydrogen bromide (a total of 1.9
grams) was introduced into the reaction zone, along with the oxygen. The
reaction was allowed to continue for 6 hours following which the reaction
mixture was distilled. Essentially complete conversion of the allyl acetate took
place. A yield of 116 grams of glycerol triacetate was obtained, this being
accomplished by distilling the glycerol triacetate overhead from the reaction
mixture, at an absolute pressure of approximately 13 mm of mercury.
Therapeutic Function
Topical antifungal
Taste threshold values
Sweet and creamy with an oily mouthfeel.
General Description
Triacetin is a triester of glycerin and acetic acid that occurs naturally in papaya. It is mainly used as a synthetic flavoring agent in ice-creams, nonalcoholic beverages and baked goods.
Pharmaceutical Applications
Triacetin is mainly used as a hydrophilic plasticizer in both aqueous
and solvent-based polymeric coating of capsules, tablets, beads, and
granules; typical concentrations used are 10–35% w/w.
Triacetin is used in cosmetics, perfumery, and foods as a solvent
and as a fixative in the formulation of perfumes and flavors.
Clinical Use
Glyceryl triacetate (Enzactin, Fungacetin) is a colorless, oilyliquid with a slight odor and a bitter taste. The compound issoluble in water and miscible with alcohol and most organicsolvents.
The activity of triacetin is a result of the acetic acid releasedby hydrolysis of the compound by esterases presentin the skin. Acid release is a self-limiting process becausethe esterases are inhibited below pH 4.
Safety
Triacetin is used in oral pharmaceutical formulations and is
generally regarded as a relatively nontoxic and nonirritant material
at the levels employed as an excipient.
LD50 (dog, IV): 1.5 g/kg
LD50 (mouse, IP): 1.4 g/kg
LD50 (mouse, IV): 1.6 g/kg
LD50 (mouse, oral): 1.1 g/kg
LD50 (mouse, SC): 2.3 g/kg
LD50 (rabbit, IV): 0.75 g/kg
LD50 (rat, IP): 2.1 g/kg
LD50 (rat, oral): 3 g/kg
LD50 (rat, SC): 2.8 g/kg
in vitro
Litton Bionetics, Inc. (1976) evaluated the mutagenic potential of Triacetin in a plate test using Salmonella typhimurium
strains TA1535, TA1537, and TA1538 with and without metabolic activation. Test concentrations were 0.0013%, 0.00065%,
and 0.000325% and the solvent was dimethyl sulfoxide (DMSO).
A negative control (solvent) and appropriate positive controls
were used and gave expected results. Triacetin was not mutagenic with or without metabolic activation.
Unichema Chemie B.V. (1994) reported that Triacetin was
not mutagenic at 50 to 5000 μg/plate in an Ames test using S.
typhimurium strains TA1535, TA1537, TA98, and TA100 with
and without metabolic activation.
in vivo
The mutagenic potential of Triacetin was determined using
adult Drosophila melanogaster (Efremova 1962). A dose of 0.2
to 0.3 mg Triacetin had a spontaneous mutation rate of approximately one mutation per 750 chromosomes.
storage
Triacetin is stable and should be stored in a well-closed, nonmetallic
container, in a cool, dry place.
Incompatibilities
Triacetin is incompatible with metals and may react with oxidizing
agents. Triacetin may destroy rayon fabric.
Regulatory Status
GRAS listed. Accepted in Europe as a food additive in certain
applications. Included in the FDA Inactive Ingredients Database
(oral capsules and tablets and gels). Included in nonparenteral
medicines licensed in the UK. Included in the Canadian List of
Acceptable Non-medicinal Ingredients.
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