Estimation of drug solubility in water, PEG 400 and their binary mixtures using the molecular structures of solutes

Ghafourian, Taravat and Bozorgi, A.H.A. (2010) Estimation of drug solubility in water, PEG 400 and their binary mixtures using the molecular structures of solutes. European Journal of Pharmaceutical Sciences, 40 (5). pp. 430-440. ISSN 0928-0987

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Abstract

With the aim of solubility estimation in water, polyethylene glycol 400 (PEG) and their binary mixtures, quantitative structure-property relationships (QSPRs) were investigated to relate the solubility of a large number of compounds to the descriptors of the molecular structures. The relationships were quantified using linear regression analysis (with descriptors selected by stepwise regression) and formal inference-based recursive modeling (FIRM). The models were compared in terms of the solubility prediction accuracy for the validation set. The resulting regression and FIRM models employed a diverse set of molecular descriptors explaining crystal lattice energy, molecular size, and solute-solvent interactions. Significance of molecular shape in compound's solubility was evident from several shape descriptors being selected by FIRM and stepwise regression analysis. Some of these influential structural features, e.g. connectivity indexes and Balaban topological index, were found to be related to the crystal lattice energy. The results showed that regression models outperformed most FIRM models and produced higher prediction accuracy. However, the most accurate estimation was achieved by the use of a combination of FIRM and regression models. The results also showed that the use of melting point in regression models improves the estimation accuracy especially for solubility in higher concentrations of PEG. Aqueous or PEG/water solubilities can be estimated by these models with root mean square error of below 0.70. © 2010 Elsevier B.V.

Item Type: Article
Keywords: allopurinol; azathioprine; caffeine; guanine; macrogol 400; solvent; strychnine; uric acid; water; xanthine; drug; macrogol derivative; solution and solubility; water, accuracy; analytical error; aqueous solution; article; chemical structure; crystal structure; drug solubility; molecular interaction; molecular size; prediction; priority journal; quantitative structure property relation; solute; statistical model; validation study; chemistry; quantitative structure activity relation; regression analysis; solubility; solution and solubility, Molecular Structure; Pharmaceutical Preparations; Polyethylene Glycols; Quantitative Structure-Activity Relationship; Regression Analysis; Solubility; Solutions; Solvents; Water, Molecular Structure; Pharmaceutical Preparations; Polyethylene Glycols; Quantitative Structure-Activity Relationship; Regression Analysis; Solubility; Solutions; Solvents; Water
Schools and Departments: School of Life Sciences > Biochemistry
Depositing User: Taravat Ghafourian
Date Deposited: 30 Nov 2017 13:09
Last Modified: 30 Nov 2017 13:09
URI: http://sro.sussex.ac.uk/id/eprint/64140

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