Thermodynamic and kinetic studies on the polymorphic transformations of puerarin hydrates

Puerarin (PUE), a bioactive flavonoid from the plant Pueraria lobata, exists in two hydrated forms: monohydrate (PUEMH) and dihydrate (PUEDH). The aim of the present work was to explore the thermodynamic and kinetic mechanism of the polymorphic transformation of PUE, including the solvent-mediated polymorphic transformation (SMPT) of PUEMH to PUEDH and the solid-state polymorphic transformations (SSPTs) of PUEMH and PUEDH. PUEMH and PUEDH were identified as isolated and channel hydrate, respectively. The thermodynamic parameters (ΔG < 0, ΔH < 0, and ΔS < 0) indicated that the SMPT was a spontaneous, exothermic and entropy-decreased reaction. The facilitating roles of stirring rate and temperature on the SMPT were favored by the primary and secondary nucleation process of PUEDH. In addition, the results of SSPTs suggested that PUEMH and PUEDH would transform to two different anhydrates (PUEAH-I and PUEAH-II) upon heating, respectively. The dehydration rate of PUEMH was slower than that of PUEDH due to the stronger hydrogen bond interactions. The rate-limiting step for the dehydration of PUEMH was the diffusion of water molecules, resulting in the increased dehydration activation during the dehydration process, while the dehydration activation energy of PUEDH showed opposite trend due to the complicated crystallization process of PUEAH-II.