Influence of particle size on the crystallization kinetics of amorphous felodipine powders

The goal of this study was to investigate the influence of particle size on the crystallization kinetics of amorphous felodipine powders stored below the glass transition temperature and to evaluate the role of surface versus bulk crystallization in influencing the kinetic profiles. Raman spectroscopy and powder X-ray diffraction (PXRD) were used to monitor the crystallization of different particle size fractions of pure amorphous felodipine and solid dispersions containing 3 wt.% polyvinyl pyrrolidone (PVP) stored at 30 °C. Optical microscopy was employed to measure surface and bulk growth rates of felodipine in the absence and presence of PVP at 30 °C. Solution concentration-time profiles for the various samples prior to and after crystallization were also measured. The growth rate of felodipine from the free surface was approximately 6 times faster than from the bulk in the absence of any polymer while the ratio of the surface to bulk growth rates was 23 in the presence of PVP. The overall crystallization rates of the amorphous powders were particle size dependent with smaller particle sizes crystallizing faster. Felodipine alone crystallized within 7 days. However, in the presence of the polymer, crystallization was retarded and was incomplete after 6 months. For the polymer-containing powders, biphasic crystallization was observed whereby rapid initial crystallization (50–60 days) was followed by a much slower rate over the remaining time period. The initial rapid crystallization was attributed to a faster rate of surface growth. The dissolution profiles of the different powders were dependent on both the particle size and the extent of crystallinity, with the level of supersaturation achieved varying considerably.

Crystallization kinetics as a function of particle size was monitored for amorphous powders using Raman spectroscopy and powder X-ray diffraction. Crystallization rates were particle size dependent. Polymer containing powders showed biphasic crystallization. Faster initial crystallization was attributed to a faster rate of surface growth. The impact of surface area on crystallization is therefore an important consideration for physical stability.Figure optionsDownload as PowerPoint slide