University of Sussex
Browse
Ghafourian-EJPS-rev.pdf (715.8 kB)

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

Download (715.8 kB)
journal contribution
posted on 2023-06-09, 03:26 authored by Taravat Ghafourian, A.H.A. Bozorgi
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.

History

Publication status

  • Published

File Version

  • Accepted version

Journal

European Journal of Pharmaceutical Sciences

ISSN

0928-0987

Publisher

Elsevier

Issue

5

Volume

40

Page range

430-440

Department affiliated with

  • Biochemistry Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2017-11-30

First Open Access (FOA) Date

2017-11-30

First Compliant Deposit (FCD) Date

2017-11-30