Predicting the excess solubility of acetanilide, acetaminophen, phenacetin, benzocaine, and caffeine in binary water/ethanol mixtures via molecular simulation.
Predicting the excess solubility of acetanilide, acetaminophen, phenacetin, benzocaine, and caffeine in binary water/ethanol mixtures via molecular simulation.
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DOI：
10.1063/1.4906491
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发表时间：
2015-01
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影响因子：
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通讯作者：
Andrew S. Paluch;Sreeja Parameswaran;Shuai Liu;Anasuya Kolavennu;D. Mobley
中科院分区：
文献类型：
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作者：
Andrew S. Paluch;Sreeja Parameswaran;Shuai Liu;Anasuya Kolavennu;D. Mobley
通过分子模拟自由能计算，结合传统分子模型，给出了预测小分子固体(如药物固体)在二元溶剂中的过量溶解度的一般框架。本研究采用分子动力学与一般琥珀力场相结合的方法，预测了乙酰苯胺、对乙酰氨基酚、非那西丁、苯佐卡因和咖啡因在水/乙醇二元溶剂中的过量溶解度。模拟结果能较好地预测增溶作用的存在，模拟结果与已有的实验数据吻合较好。除了该方法的一般性外，预测的准确性表明，分子模拟可能是药物开发过程中选择溶剂的有价值的设计工具。
We present a general framework to predict the excess solubility of small molecular solids (such as pharmaceutical solids) in binary solvents via molecular simulation free energy calculations at infinite dilution with conventional molecular models. The present study used molecular dynamics with the General AMBER Force Field to predict the excess solubility of acetanilide, acetaminophen, phenacetin, benzocaine, and caffeine in binary water/ethanol solvents. The simulations are able to predict the existence of solubility enhancement and the results are in good agreement with available experimental data. The accuracy of the predictions in addition to the generality of the method suggests that molecular simulations may be a valuable design tool for solvent selection in drug development processes.