科研之友
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摘要
Pharmaceutical hydrates have been used as clinical development candidates and in marketed products. The physical stability of hydrates can pose unique challenges to their development because of their particular sensitivity to the moisture levels in their surroundings. By conducting simple experiments early during the form selection phase of a drug candidate's development, a basic understanding of the thermodynamic and kinetic aspects of a hydrate form's stability can be attained that can facilitate the successful navigation of these challenges. Differential scanning calorimetry was used to determine the thermal and kinetic properties of a number of pharmaceutically relevant hydrates. The activation energy (Ea) of dehydration and dehydration onset temperature (Tonset) of survey compounds were compiled and analyzed. A significant number of compounds possessed both high Ea and high Tonset of dehydration, suggesting that these hydrate crystal forms were particularly stable. The results of these studies suggest that dehydration Ea and dehydration Tonset together can be used as early indicators of a crystalline hydrate's physical stability and can alert to potential challenges in developing hydrate crystal forms of drug candidates.
- 出版日期2012-10
