Insights into Cocrystallization and Coamorphization Engineering Techniques in the Delivery of Traditional Chinese Medicine: Formation Mechanism, Solid-State Characterization, and Improved Pharmaceutical Properties

Many active ingredients from traditional Chinese medicine (TCM) exhibit poor pharmaceutical properties (e.g., low aqueous solubility, slow dissolution, low bioavailability, poor stability, and high hygroscopicity, etc.), which are closely associated with various formulation performance issues. Cocrystals or coamorphous systems, incorporating drug and guest molecules into a homogeneous single crystalline or amorphous phase, have been shown to offer potential advantages in enhancing pharmaceutical properties of TCM. This review outlines the definition, classification, preparation methods, characterization techniques, and pharmaceutical properties (such as solubility, dissolution, stability, mechanical properties, permeability, and in vivo performance) of cocrystals and coamorphous systems. More insights into the formation mechanisms of cocrystals and coamorphous systems, the identification of single-phase homogeneous coamorphous systems, and the characterization of their intermolecular interactions between components are covered. Latest research studies on the delivery of TCM via cocrystallization and coamorphization technologies are also summarized. The mechanisms of enhancement in druggability-related properties through cocrystals and coamorphous systems are further discussed. In particular, several common kinetic solubility behaviors of cocrystal and coamorphous systems, including "spring and parachute" and "spring and hover" models, are deeply understood, which will contribute to the maintenance of high supersaturation and in vivo bioavailability.