Evaluation of the Crystal Growth Rate of Felodipine Polymorphs in the Presence and Absence of Additives As a Function of Temperature

The purpose of the present study was to compare the effect of temperature and a polymeric additive, poly(vinyl pyrrolidone) (PVP), on the crystal growth rate of two polymorphs of felodipine from amorphous samples Comparing the growth rates of the two polymorphs in the presence of PVP should provide mechanistic information on whether PVP inhibits crystal growth of felodipine by interacting at the crystal surface of felodipine or in the amorphous regions. Optical microscopy was used to measure the growth rates at various temperatures in the range of 18-100 degrees C for the form I polymorph and 40-100 degrees C for the form II polymorph. Both surface and bulk growth rates for the form I polymorph were evaluated, while for the form II polymorph, only the bulk growth rate could be studied. No difference in the growth rate between surface and bulk crystals of form I was observed at higher temperatures (>70 degrees C). However, below 65 degrees C the surface crystal growth rate was faster than the bulk crystal growth rate. Another mode of growth rate was activated for the form I polymorph near the glass transition temperature of felodipine. In the absence of any polymer, the bulk growth rate of felodipine form I polymorph was faster than that of form II by 1-2 orders of magnitude. PVP was found to reduce the crystal growth rate of both polymorphs at all temperatures The ratio of the growth rate of felodipine in the absence of any polymer to that in the presence of PVP for both polymorphs appear to be similar in the temperature range 60-100 degrees C indicating that the inhibitory effect of PVP on felodipine crystal growth most likely arises from an effect on the amorphous material rather than at the crystal surface.