Influence of the Polymer Glass Transition Temperature and Molecular Weight on Drug Amorphization Kinetics Using Ball Milling

In this study, the putative correlation between the molecular mobility of a polymer and the ball milling drug amorphization kinetics (i.e., time to reach full drug amorphization, t(a)) was studied using different grades of dextran (Dex) and polyvinylpyrrolidone (PVP) and the two model drugs indomethacin (IND) and chloramphenicol (CAP). In general, IND had lower t(a) values than CAP, indicating that IND amorphized faster than CAP in the presence of the polymers. In addition, an increase in polymer molecular weight (M(w)) also led to an increase in t(a) for all systems investigated up to a critical M(w) for each polymer, which was in line with an increase of the glass transition temperature (T(g)) up to the critical M(w) of each polymer. Hence, the increase in t(a) seemed to correlate well with the T(g)/M(w) of the polymers, which indicates that the polymers’ molecular mobility had an influence on the drug amorphization kinetics during ball milling.