Investigation of fatty acid esters to replace isopropyl myristate in the sterility test for ophthalmic ointments
Investigation of fatty acid esters to replace isopropyl myristate in the sterility test for ophthalmic ointments
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DOI：
10.1016/j.jpba.2006.05.018
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发表时间：
2006-11-16
影响因子：
3.4
通讯作者：
Nunan, Elziria de Aguiar
中科院分区：
文献类型：
--
作者：
Cardoso, Valeria Macedo;Reis Solano, Ana Gabriela;Nunan, Elziria de Aguiar
多部药典推荐采用薄膜过滤法进行眼膏的无菌检查。肉豆蔻酸异丙酯是一种脂肪酸酯，主要对革兰氏阴性微生物具有高毒性，可用作软膏剂的溶剂。在本研究中，评价了6种脂肪酸酯（己二酸二乙酯、己二酸二异丙酯、月桂酸乙酯、肉豆蔻酸乙酯、辛酸甲酯和棕榈酸异丙酯）作为眼用软膏无菌检查中替代肉豆蔻酸异丙酯的溶剂。脂肪酸酯的分配系数的对数（log P）由其分子中存在的官能团的取代基疏水性常数（pi）的总和计算。研究了溶剂溶解眼用软膏基质的能力。采用D值法评价棕榈酸异丙酯、肉豆蔻酸乙酯、月桂酸乙酯和肉豆蔻酸异丙酯对铜绿假单胞菌的抗菌活性。棕榈酸异丙酯是对该微生物毒性最小的溶剂，因为它具有最高的D值（171.1 min）。肉豆蔻酸乙酯（89.4 min）和肉豆蔻酸异丙酯（92.5 min）的D值之间未观察到显著差异。月桂酸乙酯显示出最低的D值（27.2 min）。使用气相色谱-质谱联用，检测到其他脂肪酸酯作为溶剂中的主要杂质，以及少量或微量的酸污染物。(c)2006 Elsevier B. V.保留所有权利。
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 (log P) 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. (c) 2006 Elsevier B.V. All rights reserved.