Nonproprietary Names

USP-NF: Acetyltriethyl Citrate

Synonyms

ATEC; Citroflex A-2; triethyl acetylcitrate; triethyl O-acetylcitrate; triethyl citrate acetate.

Chemical Name and CAS Registry Number

1,2,3-Propanetricarboxylic acid, 2-acetyloxy, triethyl ester [77-894]

Empirical Formula and Molecular Weight

C14H22O8 318.3

Structural Formula

Functional Category

Plasticizer.

Applications in Pharmaceutical Formulation or Technology

Technology Acetyltriethyl citrate is used to plasticize polymers in formulated pharmaceutical coatings.(1) The coating applications include capsules, tablets, beads and granules for taste masking, immediate release, sustained-release and enteric formulations.(2–5) It is also used in diffusion-controlled release drug delivery systems.(6)

Description

Acetyltriethyl citrate occurs as a clear, odorless, practically colorless oily liquid.

Pharmacopeial Specifications

See Table I. Table I: Pharmacopeial specifications for acetyltriethyl citrate. Test USP32–NF27 Identification Specific gravity þ1.135–1.139 Refractive index 1.432–1.441 Acidity Water þ40.3% Heavy metals 40.001% Assay (anhydrous basis) 599.0%

Typical Properties

Acid value 0.02 Boiling point 2948C (decomposes) Flash point 1888C Pour point 438C Solubility Soluble 1 in 140 of water; miscible with acetone, ethanol, and propan-2-ol. Viscosity (dynamic) 54mPas (54cP) at 258C.

Stability and Storage Conditions

Acetyltriethyl citrate should be stored in dry, closed containers at temperatures not exceeding 388C. When stored in accordance with these conditions, acetyltriethyl citrate is a stable product.

Incompatibilities

Acetyltriethyl citrate is incompatible with strong alkalis and oxidizing materials.

Method of Manufacture

Acetyltriethyl citrate is prepared by the esterification of citric acid with ethanol followed by acylation with acetic anhydride.

Safety

Acetyltriethyl citrate is used in oral pharmaceutical formulations and is generally regarded as a nontoxic and nonirritating material. However, ingestion of large quantities may be harmful. LD50 (cat, oral): 8.5g/kg(7) LD50 (mouse, IP): 1.15g/kg LD50 (rat, oral): 7g/kg

Handling Precautions

Observe normal precautions appropriate to the circumstances and quantity of material handled. Acetyltriethyl citrate may be irritating to the eyes or the respiratory system as a mist or at elevated temperatures. Gloves and eye protection are recommended for normal handling and a respirator is recommended if used at elevated temperatures.

Regulatory Status

Approved in the USA for direct food contact in food films. 17 Related Substances Acetyltributyl citrate; tributyl citrate; triethyl citrate.

Comments

The EINECS number for acetyltriethyl citrate is 201-066-5. The 10 PubChem Compound ID (CID) for acetyltriethyl citrate is 6504. 19 Specific References 1 Jensen JL et al. Variables that affect the mechanism of drug release from osmotic pumps coated with acrylate/methacrylate copolymer latexes. J Pharm Sci 1995; 84: 530–533. 2 Gutierrez-Rocca JC, McGinity JW. Influence of water soluble and insoluble plasticizer on the physical and mechanical properties of acrylic resin copolymers. Int J Pharm 1994; 103: 293–301. 3 Lehmann K. Chemistry and application properties of polymethacrylate coating systems. McGinity JW, ed. Aqueous Polymeric Coatings for Adipic Acid 11 4 5 6 7 Pharmaceutical Dosage Forms. New York: Marcel Dekker, 1989; 153– 245. Steurnagel CR. Latex emulsions for controlled drug delivery. McGinity JW, ed. Aqueous Polymeric Coatings for Pharmaceutical Dosage Forms. New York: Marcel Dekker,1–61. Gutierrez-Rocca JC, McGinity JW. Influence of aging on the physicalmechanical properties of acrylic resin films cast from aqueous dispersions and organic solutions. Drug Dev Ind Pharm 1993; 19(3): 315–332. Siepmann J et al. Diffusion-controlled drug delivery systems: calculation of the required composition to achieve desired release profiles. J Control Release 1999; 60(2–3): 379–389. Lewis RJ, ed. Sax’s Dangerous Properties of Industrial Materials, 11th edn. New York: Wiley, 2004; 58–59.

General References

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Author

s ME Quinn, PJ Sheskey.

Date of Revision

18 February 2009.