Preparation of Baicalin Nanocrystals Using an Impinging Jet Crystallizer

Baicalin as a flavonoid compound exhibits diverse and significant pharmacological activities. Nevertheless, its intrinsically poor aqueous solubility has been an obstacle to its clinical application. To overcome this limitation, this study devised an innovative crystallization strategy, thereby enabling the controllable synthesis of baicalin nanocrystals. Initially, the crystallization process of baicalin microcrystals in a stirred tank crystallizer was optimized, and the effects of parameters such as additive types, equivalents, stirring rates, and crystallization temperatures on the particle size and morphology of crystals were explored. Subsequently, technologies including X-ray diffraction (XRD), proton nuclear magnetic resonance spectroscopy (¹H NMR), online microscopy imaging, and pH monitoring were utilized to elucidate the crystallization mechanism of baicalin, thereby laying the theoretical foundation for the preparation of baicalin nanocrystals. Finally, this study innovatively introduced an impinging jet crystallizer, based on the foregoing research findings. In contrast to the traditional reactors, this device integrates the advantages of both impinging jet reactor and batch crystallizer, which can simultaneously strengthen the micro- and macro-mixing processes. This dual-scale modulation strategy achieves precise kinetic control by synchronizing nucleation enhancement with growth suppression and regulation. To identify the optimal process parameters of the impinging jet crystallizer, a computational fluid dynamics (CFD) simulation and experimental research were combined. Eventually, the baicalin nanocrystals featuring an average particle size of less than 300   nm and spherical morphology were successfully prepared.