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
journal contribution
posted on 2023-06-09, 03:26 authored by Taravat Ghafourian, A.H.A. BozorgiWith 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 SciencesISSN
0928-0987Publisher
ElsevierExternal DOI
Issue
5Volume
40Page range
430-440Department affiliated with
- Biochemistry Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2017-11-30First Open Access (FOA) Date
2017-11-30First Compliant Deposit (FCD) Date
2017-11-30Usage metrics
Categories
No categories selectedKeywords
allopurinol; azathioprine; caffeine; guanine; macrogol 400; solvent; strychnine; uric acid; water; xanthine; drug; macrogol derivative; solution and solubility; wateraccuracy; 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 solubilityMolecular Structure; Pharmaceutical Preparations; Polyethylene Glycols; Quantitative Structure-Activity Relationship; Regression Analysis; Solubility; Solutions; Solvents; Water
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC