The Physical Stability of Amorphous Nifedipine Determined by Isothermal Microcalorimetry.

Abstract

The applicability of isothermal microcalorimetry to evaluation of the physical stability of amorphous nifedipine was examined. Amorphous nifedipine was obtained by fusion and subsequent rapid cooling, and its crystallization heat at a constant temperature was measured using a heat-conductive microcalorimeter. The heat production due to crystallization of amorphous nifedipine and the transformation of its metastable crystalline form into a stable crystalline one was detected at a temperature above its glass transition temperature T_g). The time required for half an amorphous nifedipine sample to be crystallized (t₅₀) was calculated from the heat production time profile, and the reciprocal of t₅₀ (1/t₅₀) was used as a measure of the crystallization rate, which increased as the temperature increased. The Williams, Landel and Ferry (WLF) plot of 1/t₅₀ was linear, indicating that the crystallization rate was affected by the nifedipine matrix viscosity, which decreased as the temperature increased. Moisture decreased the T_g of the fused nifedipine and increased its crystallization rate. The effects of temperature and humidity can be interpreted by changes in the matrix viscosity, which is related to the molecular motion of nifedipine.