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.

Tailor-made solvents for pharmaceutical use? Experimental and computational approach for determining solubility in deep eutectic solvents (DES).

A deep eutectic solvent (DES) is a mixture of two or more chemicals that interact via hydrogen bonding and has a melting point far below that of the individual components. DESs have been proposed as alternative solvents for poorly soluble active pharmaceutical ingredients (API). In this study, the solvation capacities of six deep eutectic solvents were compared to water and three conventional pharmaceutical solvents (PEG 300, ethanol and glycerol) for 11 APIs. The experimentally determined solubilities were compared to computational solubilities predicted by the Conductor-like Screening Model for Real Solvents (COSMO-RS). While the conventional pharmaceutical solvents PEG 300 and ethanol were the best solvents for the majority of the studied APIs, API-DES combinations were identified, which exceeded the API solubility found in the conventional pharmaceutical solvents. Furthermore, it was also possible to obtain high solubilities in the DESs relative to water, suggesting DESs to be potential solvents for poorly water soluble APIs. In addition, the relative increase in solubility found in the experimental data could be well predicted ab initio using COSMO-RS. Hence, COSMO-RS may in the future be used to reduce the experimental screening of potential DESs for a given API.