Compendium of the most significant studies with reference to properties, intake, effects.

Johnson W Jr. Final report on the safety assessment of acetyl triethyl citrate, acetyl tributyl citrate, acetyl trihexyl citrate, and acetyl trioctyl citrate. Int J Toxicol. 2002;21 Suppl 2:1-17. doi: 10.1080/10915810290096504. 

Gzyra-Jagieła K, Sulak K, Draczyński Z, Podzimek S, Gałecki S, Jagodzińska S, Borkowski D. Modification of Poly(lactic acid) by the Plasticization for Application in the Packaging Industry. Polymers (Basel). 2021 Oct 23;13(21):3651. doi: 10.3390/polym13213651.

Herrera N, Singh AA, Salaberria AM, Labidi J, Mathew AP, Oksman K. Triethyl Citrate (TEC) as a Dispersing Aid in Polylactic Acid/Chitin Nanocomposites Prepared via Liquid-Assisted Extrusion. Polymers (Basel). 2017 Aug 31;9(9):406. doi: 10.3390/polym9090406.

Pinho LAG, Lima AL, Sa-Barreto LL, Gratieri T, Gelfuso GM, Marreto RN, Cunha-Filho M. Preformulation Studies to Guide the Production of Medicines by Fused Deposition Modeling 3D Printing. AAPS PharmSciTech. 2021 Nov 2;22(8):263. doi: 10.1208/s12249-021-02114-7. 

Budavári Z, Porkoláb Z, Zelkó R. Study of triethyl citrate migration from coating polymers to tablet cores. Pharmazie. 2004 Nov;59(11):893-4. 

Zhang JF, Sun X. Physical characterization of coupled poly(lactic acid)/starch/maleic anhydride blends plasticized by acetyl triethyl citrate. Macromol Biosci. 2004 Nov 20;4(11):1053-60. doi: 10.1002/mabi.200400076.

Rabek CL, Van Stelle R, Dziubla TD, Puleo DA. The effect of plasticizers on the erosion and mechanical properties of polymeric films. J Biomater Appl. 2014 Jan;28(5):779-89. doi: 10.1177/0885328213480979.

Hirasawa W, Sei S, Mineda M, Endo N, Matahira Y, Makino K, Tsukada R, Sato H, Onoue S. UniORV, a New Multi-Unit Dosage Form, Improved Biopharmaceutical Properties of Tacrolimus in Rats and Humans. Pharm Res. 2020 Mar 5;37(3):64. doi: 10.1007/s11095-020-02785-0. 

Eilers H, Alexeyev OA. Effect of GT-Peptide 10 and Triethyl Citrate on P. acnes Biofilm Formation, Viability, and Dispersion. J Drugs Dermatol. 2016 Jun 1;15(6):778-81. 

Kolter K, Dashevsky A, Irfan M, Bodmeier R. Polyvinyl acetate-based film coatings. Int J Pharm. 2013 Dec 5;457(2):470-9. doi: 10.1016/j.ijpharm.2013.08.077. 

Raone B, Veraldi S, Raboni R, Ardigò M, Patrizi A, Micali G. Salicylic acid peel incorporating triethyl citrate and ethyl linoleate in the treatment of moderate acne: a new therapeutic approach. Dermatol Surg. 2013 Aug;39(8):1243-51. doi: 10.1111/dsu.12215. 

Shimizu T, Kameoka N, Iki H, Tabata T, Hamaguchi N, Igari Y. Formulation study for lansoprazole fast-disintegrating tablet. II. Effect of triethyl citrate on the quality of the products. Chem Pharm Bull (Tokyo). 2003 Sep;51(9):1029-35. doi: 10.1248/cpb.51.1029.

Park HM, Misra M, Drzal LT, Mohanty AK. "Green" nanocomposites from cellulose acetate bioplastic and clay: effect of eco-friendly triethyl citrate plasticizer. Biomacromolecules. 2004 Nov-Dec;5(6):2281-8. doi: 10.1021/bm049690f. 

Patel M, Schwendemann D, Spigno G, Geng S, Berglund L, Oksman K. Functional Nanocomposite Films of Poly(Lactic Acid) with Well-Dispersed Chitin Nanocrystals Achieved Using a Dispersing Agent and Liquid-Assisted Extrusion Process. Molecules. 2021 Jul 28;26(15):4557. doi: 10.3390/molecules26154557. 

Van Bocxlaer K, McArthur KN, Harris A, Alavijeh M, Braillard S, Mowbray CE, Croft SL. Film-Forming Systems for the Delivery of DNDI-0690 to Treat Cutaneous Leishmaniasis. Pharmaceutics. 2021 Apr 8;13(4):516. doi: 10.3390/pharmaceutics13040516. 

Triethyl Citrate  is a chemical compound, diester of citrate (citric acid or α and β-hydroxytricarboxylic acid) alkyl with ethyl alcohol.

The industrial production of citric acid takes place by mycological fermentation of raw sugar from Aspergillus niger and subsequent crystallisation with alkaline solutions.

It appears as oily liquid soluble in water and virtually odorless.

What it is used for and where

Food 

Ingredient on the European food additives list as E1505, thickener, stabiliser.

Stabilizer of soybean oil and various seasoning oils and margarine. Flavor enhancer to improve the taste in soft drinks, desserts, cooked foods. Also can be used as a solvent for flavoring berries. Leavening agent to improve foaming properties in baked goods.

Safety

With regard to safety, Triethyl Citrate (in the form of Acetyl Triethyl Citrate) is considered relatively safe based on the toxicological data published to date, and this pharmacokinetics study demonstrated that Acetyl Triethyl Citrate rapidly disappeared from plasma. Metabolite profiling data indicated that Acetyl Triethyl Citrate was extensively metabolized and excreted primarily as metabolites rather than the parent form. This is the first report demonstrating a bioanalytical method for the determination of Acetyl Triethyl Citrate in biological samples and its pharmacokinetic properties (1).

Pharmaceutical

In tablets, it is a non-toxic hydrophilic plasticizer that can be incorporated into the film coating of pressure-coated tablets consisting of hydroxypropyl methyl cellulose acetate succinate or enteric polymer films consisting of polymethyl methacrylate. Triethyl Citrate performs the function of reducing damage during the compression process.

Cosmetics

Chelating agent, a chemical compound that reacts with metal ions to form a stable, water-soluble complex. Used as an antioxidant, solvent, deodorant, odor inhibitor and plasticizer.  Skin care products plasticized with Triethyl Citrate have good resistance to oil, light and mildew.

Medical

It is used in protein films composed of sunflower protein or whey protein or for buccal and sublingual films or particulate systems.

A study on hidradenitis suppurativa, a chronic disease of the terminal follicular epithelium in areas bearing apocrine glands, demonstrated the efficacy of a lotion composed of Triethyl citrate, ethyl-linoleate, and g-peptide-10. This composition had already demonstrated efficacy in the treatment of acne (2).

Plastic 

Plasticizer for thermoplastic resins such as cellulose resin, vinyl resin and soft toys. As plasticizer for adhesives and sealants, it can replace dibutyl phthalate, diisobutyl phthalate, dimethyl phthalate, diethyl phthalate, etc.

General features for liquid Triethyl Citrate

• Boiling point  235 °C/150 mmHg (lit.)
• Melting point  -55 °C
• density  1.14 g/mL at 25 °C (lit.)
• vapor density  9.7 (vs air)
• vapor pressure  1 mm Hg ( 107 °C)
• FEMA  3083 | TRIETHYL CITRATE
• refractive index  n20/D 1.442(lit.)
• Fp  >230 °F
• storage temp.  -20°C

Triethyl Citrate studies

• Molecular Formula: C₁₂H₂₀O₇
• Linear Formula: HOC(COOC₂H₅)(CH₂COOC₂H₅)₂
• Molecular Weight:  276.28
• CAS: 77-93-0
• UNII 8Z96QXD6UM
• EC Number:   201-070-7
• DSSTox Substance ID: DTXSID0040701
• MDL number  MFCD00009201
• PubChem Substance ID 329823171
• FEMA   3083
• Bellstein: 1801199
• NACRES  NA.24

Synonyms: 

• Ethyl citrate
• Citric acid, triethyl ester

References__________________________________________________________________

(1) Kim H, Ji YS, Rehman SU, Choi MS, Gye MC, Yoo HH. Pharmacokinetics and Metabolism of Acetyl Triethyl Citrate, a Water-Soluble Plasticizer for Pharmaceutical Polymers in Rats. Pharmaceutics. 2019 Apr 3;11(4):162. doi: 10.3390/pharmaceutics11040162.

(2) Skroza N, Mambrin A, Tolino E, Marchesiello A, Proietti I, Bernardini N, Potenza C. Efficacy and tolerability of a lotion containing triethyl citrate, ethyl linoleate, and GT peptide-10 in the adjuvant treatment of hidradenitis suppurativa: Real-life data. Dermatol Ther. 2018 Jul;31(4):e12599. doi: 10.1111/dth.12599.