Cocrystallization of Active Pharmaceutical Ingredients Derived from Traditional Chinese Medicines

This review highlights the cocrystals of active pharmaceutical ingredients (APIs) derived from traditional Chinese medicines (TCMs) in categories, ∆pK_a rule, preparation, characterization, and physicochemical properties, reported in 113 literature reports. It is founded that the formation of all of the cocrystals is in accordance with ∆pK_a rule. Three preparation methods such as evaporation cocrystallization, grinding method, and suspension method, are used most, accounting for 44, 27, and 16%, respectively. Almost all cocrystals are characterized by powder X-ray diffraction (PXRD). Thermal analysis techniques are used for 81% of cocrystals, and more than half of cocrystals are characterized by IR. Forty-four percent of cocrystals are determined by single crystal X-ray diffraction (SXRD) since it is difficult to get the single crystals of cocrystals. Most cocrystals of APIs in TCMs exhibit 1-10 folds enhancement in solubility, dissolution, dissolution rate, and bioavailability, and a few of them are increased by dozens or even hundreds of times in these properties. This review provides a meaningful reference for more and more APIs in TCMs prepared for pharmaceutical cocrystals in future.