Journal of Pharmaceutical Sciences 2014-02-01

Inversion of population distribution of felodipine conformations at increased concentration in dimethyl sulfoxide is a prerequisite to crystal nucleation.

Ilya A Khodov, Sergey V Efimov, Michael Yu Nikiforov, Vladimir V Klochkov, Nikolaj Georgi

Index: J. Pharm. Sci. 103(2) , 392-4, (2014)

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Abstract

Knowledge of the preferred conformations of biologically active compounds is of the utmost importance for a better understanding of the structure-activity relationships underlying their biological activity, as well as their mechanism of action. Moreover, investigating the mechanism of nucleation from a saturated solution can facilitate the discovery and preparation of new polymorphic forms. To search regularities in the crystal nucleation of biologically active compounds (drugs) from a saturated solution, we studied the conformational preference of felodipine in dilute and saturated solution in dimethyl sulfoxide. The inversion of conformation distribution at increased concentration occurs: conformers that dominate in a dilute solution become the least abundant in the saturated one. Conformers that dominate in the saturated solution are of the same type as revealed in crystalline state by X-ray.© 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.