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, ta) 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 ta values than CAP, indicating that IND amorphized faster than CAP in the presence of the polymers. In addition, an increase in polymer molecular weight (Mw) also led to an increase in ta for all systems investigated up to a critical Mw for each polymer, which was in line with an increase of the glass transition temperature (Tg) up to the critical Mw of each polymer. Hence, the increase in ta seemed to correlate well with the Tg/Mw of the polymers, which indicates that the polymers' molecular mobility had an influence on the drug amorphization kinetics during ball milling.

Using dextran of different molecular weights to achieve faster freeze-drying and improved storage stability of lactate dehydrogenase.

Freeze-drying of protein formulations is frequently used to maintain protein activity during storage. The freeze-drying process usually requires long primary drying times because the highest acceptable drying temperature to obtain acceptable products is dependent on the glass transition temperature of the maximally freeze-concentrated solution (Tg'). On the other hand, retaining protein activity during storage is related to the glass transition temperature (Tg) of the final freeze-dried product. In this study, dextrans with different molecular weight (1 and 40 kDa) and mixtures thereof at the ratio 3:1, 1:1, and 1:3 (w/w) were used as cryo-/lyoprotectant and their impact on the stability of the model protein lactate dehydrogenase (LDH) was investigated at elevated temperatures (40 °C and 60 °C). The dextran formulations were then compared to formulations containing sucrose as cryo-/lyoprotectant. Because of the higher Tg' values of the dextrans, the primary drying times could be reduced compared to freeze-drying with sucrose. Similarly, the higher Tg and Tg' of dextrans relative to sucrose led to benefits during storage which was shown through improved protection of LDH activity.