Effect of polymers on nucleation and crystal growth of amorphous acetaminophen

Abstract

While some organic molecules readily form a glass on cooling from the melt, others undergo crystallization. In this study, the underlying reason for the good glass forming ability of acetaminophen upon cooling of the melt was investigated. The impact of polymers on the crystal nucleation and growth of supercooled acetaminophen was also probed. The good glass forming ability of acetaminophen was ascribed to a separation in temperature where rapid nucleation and rapid growth occurred. Poly(acrylic acid) (PAA) and poly(vinyl pyrrolidone) (PVP) were the most effective polymers at inhibiting crystal growth. These polymers were also observed to form hydrogen bonds with acetaminophen based on infra-red spectroscopy. However, PAA was found to increase the nucleation rates while HPMCAS, which had little effect on growth, was the most effective polymer at reducing nucleation. Thus it appears that polymers can stabilize a drug in the amorphous state either by reducing crystal nucleation and/or growth. An investigation of the mechanism of stabilization is therefore important for choosing the right polymer to produce robust amorphous systems.