Tributyl Citrate

1. Nonproprietary Names

USP-NF: Tributyl Citrate

2. Synonyms

Citric acid, tributyl ester; Citroflex 4; TBC; tri-n-butyl citrate; tributyl 2-hydroxy-1,2,3-propanetricarboxylate.

3. Chemical Name & CAS Registry

1,2,3-Propanetricarboxylic acid, 2-hydroxy, tributyl ester [77-94-1]

4. Empirical Formula & Molecular Weight

C18H32O7 360.5

5. Structural Formula

6. Applications

Tributyl citrate is used to plasticize polymers in formulated pharmaceutical coatings. The coating applications include capsules, tablets, beads, and granules for taste masking, immediate release, sustained-release, and enteric formulations.(1–6)

7. Description

Tributyl citrate is a clear, odorless, practically colorless, oily liquid.

8. Pharmacopeial Specifications

See Table I.

9. Typical Properties

Acid value 0.02 Boiling point 3228C (decomposes) Flash point 1858C Pour point 628C Refractive index nD 25 = 1.443–1.445 Solubility Miscible with acetone, ethanol, and vegetable oil; practically insoluble in water. Specific gravity 1.037–1.045 for Citroflex 4. Viscosity 32 mPa s (32 cP) at 258C

10. Stability & Storage

Tributyl citrate should be stored in well-closed containers in a cool, dry location at temperatures not exceeding 388C. When stored in accordance with these conditions, tributyl citrate is a stable material.

11. Incompatibilities

Tributyl citrate is incompatible with strong alkalis and oxidizing materials.

12. Method of Manufacture

Tributyl citrate is prepared by the esterification of citric acid with butanol.

13. Safety

Tributyl citrate is used in oral pharmaceutical formulations. It is generally regarded as an essentially nontoxic and nonirritating material. However, ingestion of large quantities may be harmful. LD50 (cat, oral): >50 mL/kg(7) LD50 (mouse, IP): 2.9 g/kg LD50 (rat, oral): >30 mL/kg

14. Handling Precautions

Observe normal precautions appropriate to the circumstances and quantity of material handled. Tributyl citrate may be irritating to the eyes. It may also be irritating to the respiratory system at elevated temperatures. Gloves and eye protection are recommended for normal handling, and a respirator is recommended for elevated temperatures.

15. Regulatory Status

Approved in the USA for indirect food contact in food films. Included in the Canadian List of Acceptable Non-medicinal Ingredients.

16. Related Substances

Acetyltributyl citrate; acetyltriethyl citrate; triethyl citrate.

17. Comments

The EINECS number for tributyl citrate is 201-071-2. The PubChem Compound ID (CID) for tributyl citrate is 6507.