Abstract：
For a pair of hydrated and anhydrous crystals, the hydrate is more stable than the anhydrate when the water activity is above the critical water activity (awc). Conventional methods to determine awc are based on either hydrate-anhydrate competitive slurries at different aw or solubilities measured at different temperatures. However, these methods are typically resource-intensive and time-consuming. Here, we present simple and complementary solution- and solid-based methods and illustrate them using carbamazepine and theophylline. In the solution-based method, awc can be predicted using intrinsic dissolution rate (IDR) ratio or solubility ratio of the hydrate-anhydrate pair measured at a known water activity. In the solid-based method, awc is predicted as a function of temperature from the dehydration temperature and enthalpy obtained by differential scanning calorimetry (DSC) near a water activity of unity. For carbamazepine and theophylline, the methods yielded awc values in good agreement with those from the conventional methods. By incorporating awc as an additional variable, the hydrate-anhydrate relationship is categorized into four classes based on their dehydration temperature (Td) and enthalpy (ΔHd) in analogy with the monotropy/enantiotropy classification for crystal polymorphs. In Class 1 (ΔHd< 0 and Td ≥ 373 K), no awc exists. In Class 2 (ΔHd>0andTd≥373K), awc always exists under conventional crystallization conditions. In Class 3 (ΔHd<0andTd<373K), awc exists when T>Td. In Class 4 (ΔHd>0andTd<373K), awc exists only when T
摘要：
对于一对水合和无水的晶体，当水活度高于临界水活度(awc)时,水合物比无水物更稳定。确定awc的常规方法基于在不同aw下的水合物-无水物竞争性浆料或在不同温度下测量的溶解度。然而,这些方法通常是资源密集型和耗时的。这里,我们提出了简单和互补的基于解决方案和固体的方法，并使用卡马西平和茶碱进行了说明。在基于解决方案的方法中，awc可以使用在已知水活度下测量的水合物-无水物对的固有溶解速率(IDR)比或溶解度比来预测。在基于固体的方法中，根据脱水温度和通过差示扫描量热法（DSC）获得的焓，将awc预测为温度的函数，水分活度为1。卡马西平和茶碱，这些方法产生的awc值与常规方法的awc值非常吻合。通过将awc合并为附加变量，水合物-无水物关系根据其脱水温度（Td）和焓（ΔHd）分为四类，与晶体多晶型物的单调性/对映体分类相似。在1类(ΔHd<0和Td≥373K)中，没有awc存在。在2类(ΔHd>0和Td≥373K)中，awc总是存在于常规的结晶条件下。在第3类（ΔHd<0和Td<373K）中，当T>Td时,awc存在。在第4类（ΔHd>0和Td<373K）中，awc仅在T
