title: Investigation of fatty acid esters to replace isopropyl myristate in the sterility test for ophthalmic ointments.
abstract: Several pharmacopoeias recommend the membrane filtration method for the sterility test of ophthalmic ointments. Isopropyl myristate, a fatty acid ester that exhibits high toxicity mainly against Gram-negative microorganisms, is indicated as a solvent for ointments. In this study, six fatty acid esters (diethyl adipate, diisopropyl adipate, ethyl laurate, ethyl myristate, methyl caprylate and isopropyl palmitate) were evaluated as solvents to replace isopropyl myristate in the sterility test for ophthalmic ointments. The logarithm of the partition coefficient (logP) of the fatty acid esters was calculated from the sum of the substituent hydrophobicity constants (pi) of the functional groups present in their molecules. The ability of the solvents to dissolve an ophthalmic ointment base was investigated. The D-value method was used to assess the antimicrobial activity of isopropyl palmitate, ethyl myristate, ethyl laurate and isopropyl myristate against Pseudomonas aeruginosa. Isopropyl palmitate was the least toxic solvent to this microorganism, since it had the highest D-value (171.1 min). No significant difference was observed between the D-values of ethyl myristate (89.4 min) and isopropyl myristate (92.5 min). Ethyl laurate exhibited the lowest D-value (27.2 min). Using gas chromatography coupled to mass spectrometry, other fatty acid esters were detected as the predominant impurities in the solvents, as well as acid contaminants in low or insignificant amounts.
authors.affiliation: Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, Pampulha, Belo Horizonte 31270-901, Minas Gerais, Brazil.
authors.forename: Valéria Macedo
authors.initials: VM
authors.lastname: Cardoso
authors.forename: Ana Gabriela Reis
authors.initials: AG
authors.lastname: Solano
authors.forename: Maria Auxiliadora Fontes
authors.initials: MA
authors.lastname: Prado
authors.forename: Elzíria de Aguiar
authors.initials: Ede A
authors.lastname: Nunan
mesh_terms: D004339:Drug Compounding; D004340:Drug Contamination; D005128:Eye Diseases / Q000188:drug therapy; D005227:Fatty Acids / Q000737:chemistry / Q000494:pharmacology / Q000592:standards; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008956:Models, Chemical; D009226:Myristates / Q000737:chemistry / Q000494:pharmacology / Q000592:standards; D009824:Ointments / Q000592:standards; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D012997:Solvents / Q000737:chemistry / Q000494:pharmacology / Q000592:standards; D013242:Sterilization / Q000592:standards
chemical_list: D005227:Fatty Acids; D009226:Myristates; D009824:Ointments; D012997:Solvents; C008205:isopropyl myristate