Structural characterization, physicochemical properties, and thermal stability of three crystal forms of nifedipine

In this study the single-crystal X-ray structure of the solvated. species (nifedipine)(2) (.) 1,4-dioxane is reported for the first time. Included solvent molecules are located in isolated cavities in the crystal, yielding a very stable solvate. Desolvation of this species involves complete disruption of the crystal structure, at the relatively high temperature of 150-153degreesC, i.e., 50degrees above the boiling point of 1,4-dioxane, and yields a monoclinic polymorph (Modification I) with a melting point of 174degreesC. When exposed to an aqueous medium for 48 h, the solvate transformed into a dihydrate. The aqueous solubilities of the above species were in the order: 1,4-dioxane solvate greater than or equal to Modification I > dihydrate. The solubility of nifedipine was increased sixfold when transformed into an amorphous form by quenched fusion. This amorphous form was relatively stable at room temperature but converted to Modification I when suspended in water at pH1. The fused materials also converted to Modification I through an intermediate, Modification III, within 6 days when kept at 40degreesC for 6 days. XRPD analysis showed that grinding increased the crystallinity of the amorphous form due to partial transformation to Modification L The, pulverized amorphous powder was more stable at 40degreesC and was approximately three times as soluble as Modification I. (C) 2003 Wiley-Liss, Inc.