Abstract
Background: Solubility of drugs is an important issue in pharmaceutical industry and the solubility of polymorphs play a critical role in dealing with the solubility issue. This work summerizes the effects of crystal structure on drug’s solubility with special focus on the modeling approaches.
Methods: The reported solubility data of polymorphs of drugs (i.e. buspirone HCl, clopidogrel hydrogen sulfate, dabigatran exetilate mesylate, flufenamic acid, glycine, indomethacin, mefenamic acid and sofosbuvir) in mono-/mixed-solvent systems were collected from the literature. The data and modeling results were briefly reviewed and the solubility ratios of the polymorphs were calculated. The applicability of the proposed cosolvency models to simulate the solubility of different polymorphs of a solute in mono- or mixed-solvents at various temperatures were shown employing the collected data. The accuracy of the models was assessed by computing the mean percentage deviations (MPDs) of the simulated and measured solubilities.
Results: The overall MPD for correlated solubility data of polymorphs of drugs in mono-solvents at various temperatures using a correlative multi-parameter model was 8.9% and that for mixed-solvents using the Jouyban-Acree model was 6.7%. The results of predictions in mixed-solvents provided acceptable errors (overall MPD of 16.6%) and could be recommended for practical applications in the industry.
Conclusion: The provided computational methods provided satisfactory results and could be considered as practical solution in the industrial applications.