Effects of Moisture on the Growth Rate of Felodipine Crystals in the Presence and Absence of Polymers

Abstract

The purpose of this study was to examine how moisture affects the growth rate of felodipine crystals from amorphous systems. Amorphous felodipine films with 0−10% w/w poly(vinylpyrrolidone) (PVP) or hypromellose acetate succinate (HPMCAS) were prepared by spin coating and stored at room temperature at different relative humidities (RHs). Linear growth rates were determined using optical microscopy. Crystals grown from felodipine alone had the fastest growth rate under all conditions. An approximately log−linear relationship between crystal growth rate and storage RH was observed between 13% and 80% RH. Above 80% RH, an abrupt 15−40-fold increase in growth rate occurred, producing crystals of a different morphology. Polymeric additives decreased crystal growth rates, more so with increasing polymer concentration. Growth rates from PVP-containing films increased with increasing storage RH, but thosefor HPMCAS systems did not. Below 52% RH, PVP was the better growth inhibitor; above 64% RH, HPMCAS inhibited crystal growth more effectively. At high RH, the dependence of crystal growth rate on PVP concentration was vastly reduced probably as a result of moisture-induced drug−polymer phase separation.Polymeric additives were thus found to inhibit the crystal growth rate of felodipine in the presence of moisture, with the extent of the inhibition dependent on a number of different factors.