Synergic Effects of Polymeric Additives on Dissolution and Crystallization of Acetaminophen

Abstract

To study how polymeric additives interact with the crystal surface of acetaminophen, and why they have different effects on drug crystallization and dissolution. The effects of different polymers on the etching patterns, crystallization and intrinsic dissolution rate (IDR) of acetaminophen have been studied. Some polymers have shown clear consistency in their effects on the etching patterns, crystallization and IDR of acetaminophen. For example, hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC) and polyvinylpyrrolidone (PVP), not only changed the etching patterns of the acetaminophen (010) face, but also inhibited acetaminophen crystallization significantly. Some polymers, like 2-hydroxyethyl cellulose (HEC), poly(vinyl alcohol) (PVA) and poly(ethylene glycol) (PEG) only had limited effects on the IDR and etching patterns, and no significant inhibitory effects on crystallization. Even though some polymeric additives have no structural similarity to acetaminophen, they still can affect dissolution and crystallization of acetaminophen due to the synergic effects of their neighboring subunits during surface adsorption. The effects of polymeric additives on crystallization and dissolution of acetaminophen are affected not only by the specific interactions between adsorbed polymer molecules and crystal surface, but also by the mobility of the functional groups involved in the specific interactions.