Acetyltriethyl Citrate

1. Nonproprietary Names

USP-NF: Acetyltriethyl Citrate

2. Synonyms

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

3. Chemical Name & CAS Registry

1,2,3-Propanetricarboxylic acid, 2-acetyloxy, triethyl ester [77-89-4]

4. Empirical Formula & Molecular Weight

C14H22O8 318.3

5. Structural Formula

6. Applications

Acetyltriethyl citrate is used to plasticize polymers in formulate 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)

7. Description

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

8. Pharmacopeial Specifications

See Table I.

9. 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) 54 mPa s (54 cP) at 258C.

10. Stability & Storage

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.

11. Incompatibilities

Acetyltriethyl citrate is incompatible with strong alkalis and oxidizing materials.

12. Method of Manufacture

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

13. 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): 8.5 g/kg(7) LD50 (mouse, IP): 1.15 g/kg LD50 (rat, oral): 7 g/kg

14. 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.

15. Regulatory Status

Approved in the USA for direct food contact in food films.

16. Related Substances

Acetyltributyl citrate; tributyl citrate; triethyl citrate.

17. Comments

The EINECS number for acetyltriethyl citrate is 201-066-5. The PubChem Compound ID (CID) for acetyltriethyl citrate is 6504.