title: Predicting the excess solubility of acetanilide, acetaminophen, phenacetin, benzocaine, and caffeine in binary water/ethanol mixtures via molecular simulation.
abstract: 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.
authors: Department of Chemical, Paper, and Biomedical Engineering, Miami University, Oxford, Ohio 45056, USA.
authors: Andrew S
authors: AS
authors: Paluch
authors: Department of Chemistry, University of New Orleans, New Orleans, Louisiana 70148, USA.
authors: Sreeja
authors: S
authors: Parameswaran
authors: Department of Pharmaceutical Sciences, University of California Irvine, Irvine, California 92697, USA.
authors: Shuai
authors: S
authors: Liu
authors: Department of Chemistry, University of New Orleans, New Orleans, Louisiana 70148, USA.
authors: Anasuya
authors: A
authors: Kolavennu
authors: Department of Pharmaceutical Sciences, University of California Irvine, Irvine, California 92697, USA.
authors: David L
authors: DL
authors: Mobley
mesh_terms: D000082:Acetaminophen / Q000737:chemistry; D000083:Acetanilides / Q000737:chemistry; D001566:Benzocaine / Q000737:chemistry; D002110:Caffeine / Q000737:chemistry; D000431:Ethanol / Q000737:chemistry*; D008958:Models, Molecular; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D010615:Phenacetin / Q000737:chemistry; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D014867:Water / Q000737:chemistry*
chemical_list: D000083:Acetanilides; D004364:Pharmaceutical Preparations; D012997:Solvents; D014867:Water; D000082:Acetaminophen; D002110:Caffeine; D000431:Ethanol; D010615:Phenacetin; C508827:acetanilide; D001566:Benzocaine
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