Solid-state characterization of nifedipine solid dispersions.

Abstract

The purpose of this study is to characterize the nature and solid-state properties of a solid dispersion system of nifedipine (33.3% w/w) in a polymer matrix consisting of Pluronic F68 (33.3% w/w) and Gelucire 50/13 (33.3% w/w). The nature of nifedipine dispersed in the matrix was studied by powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC) and diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS). The rate and extent of water uptake of the solid dispersion were determined by weight gain. The dissolution rate of nifedipine solid dispersion was determined using Apparatus 2 of USP XXIII (1995). Quantitative PXRD showed that the saturation solubility of nifedipine in the polymer matrix is 2.1-3.0% w/w and indicated an excess of crystalline nifedipine in the solid dispersion. The maximum water uptake by the solid dispersion exposed to 75% RH at 45 degrees C was 3.3 times higher than for the dispersion exposed to 65% RH at 25 degrees C. Over 8 weeks, PXRD and DRIFTS of the nifedipine matrix stored at 25 or 4 degrees C were unchanged, showing constancy of crystallinity and intermolecular interactions. For a given mass of nifedipine (20 mg) and for a given particle size of nifedipine (<850 microm), the initial release rate of nifedipine from the solid dispersion was faster (46.2% of the nifedipine dissolved in 20 min) than that of the pure drug (1.2% of the nifedipine dissolved in 20 min). The results indicate that the nifedipine solid dispersion is physically stable over 8 weeks. Nifedipine is released faster from the solid dispersion than from the pure crystalline drug of the same particle size.