Crystal growth rates and molecular dynamics of nifedipine

Abstract

The unusually fast crystallization of the organic compound nifedipine has been investigated in detail using different solutions as precursors for the formation of the initial glassy nifedipine films. Starting from these amorphous films the crystallization process was investigated by time-resolved light microscopy at different temperatures around T_g of nifedipine. In all studied cases (acetone, acetonitrile, ethyl acetate, dichloromethane, tetrahydrofuran) the measured mean crystallization rates are, on average, 10 000 times higher than rates reported in previous studies. Such high rates cannot be explained by a classical diffusional crystal growth mechanism of nifedipine. Instead, nifedipine shows a strong propensity for diffusionless growth. Solvent assisted or solvent induced preordering of the glassy modification is suggested to be the most probable driving force behind these fast crystallization processes. The nifedipine crystallization rates can be controlled not only by specific solvent–molecule interactions but also by temperature. Below 40 °C, the temperature dependence of the rates is generally small. Above 40 °C, a slowing down of the crystallization rates with increasing temperatures indicates a kinetic competition between different polymorphs. The molecular dynamics of nifedipine molecules in the amorphous phase as well as the relaxation times are studied by dielectric measurements. The dielectric data corroborate the inherently strong propensity of nifedipine to crystallize diffusionlessly under all conditions.