Role of polymer chemistry in influencing crystal growth rates from amorphous felodipine

Abstract

The inhibition of crystallization from organic amorphous solids is currently of great interest in the pharmaceutical field, since the amorphous form of the drug can enhance drug delivery. Polymers have been found to be effective crystallization inhibitors for many organic glasses and supercooled liquids. The objective of this study was to investigate potential correlations between drug–polymer hydrogen bonding and crystal growth inhibition. Quench cooled samples of a model hydrophobic drug, felodipine, were prepared with various polymers: poly(vinylpyrrolidone) (PVP), hydroxypropyl methylcellulose acetate succinate (HPMCAS), poly(vinylpyrrolidone)/vinyl acetate (PVP/VA) and poly(vinyl acetate) (PVAc). Crystal growth rates as a function of temperature (70–110 °C) were measured using optical microscopy, in the presence and absence of 3% w/w polymer. Differential scanning calorimetry (DSC) was used to evaluate glass transition temperatures (Tg) and melting points. Infrared (IR) spectroscopy was used to probe drug–polymer hydrogen bonding interactions. The various polymers were found to inhibit the crystal growth to different degrees. The order of inhibition effectiveness was PVP > PVP/VA > HPMCAS > PVAc with PVP being the best inhibitor among the polymers used. The growth rates in the presence of the polymers were similar to those of the drug alone at high temperatures but showed a significant reduction as the temperature was reduced. The Tg's of the drug–polymer dispersions were not significantly different from that of the pure drug. The order of the strength/extent of drug–polymer hydrogen bonding interactions was PVP > PVP/VA > HPMCAS ≥ PVAc. Hence polymers which can form stronger/more extensive hydrogen bonds with the drug appear to be better crystallization inhibitors.