The effect of physical state on the drug dissolution rate

Abstract

In this work, the enhancement of drug dissolution rate through the preparation of new formulations containing Nimodipine in molecular level dispersion or in nanodispersion into poly(vinyl pyrrolidone) (PVP) matrix, was investigated. Differential scanning calorimetry (DSC) and modulated-temperature differential scanning calorimetry (MTDSC) in combination with X-ray powder diffractometry (XRPD) and scanning electron microscopy (SEM) studies showed that Nimodipine was amorphous in solid dispersions of 10 or 20 mass%, and mainly dispersed on a molecular level. This behaviour is attributed to the strong interactions taking place between the amine group of Nimodipine and carbonyl group of PVP. At higher drug loadings, crystal reflections in XRPD patterns and melting peaks of Nimodipine in DSC traces, indicated presence of drug in crystalline form. Micro-Raman studies in combination with SEM micrographs showed that the mean particle size increases with drug content in the formulations, up to 10 μm. Moreover, both XRPD patterns and micro-Raman spectra seem to indicate that Nimodipine crystallized in a second, thermodynamically stable, crystal modification II. The physicochemical characteristics of Nimodipine and the particle size distribution directly affect the dissolution rate enhancement, which is higher in amorphous dispersions.