Controlling Micro/Nano Morphology and Water Solubility of Dipotassium Pyrroloquinoline Quinone via Crystal Form Modification

The dipotassium salt of pyrroloquinoline quinone (PQQK2) is a promising nutraceutical with superior stability compared to its free acid, yet the influence of its solid-state form on solubility and particle morphology has not been explored. In this study, we report a systematic investigation on controlling the micro/nano morphology and water solubility of PQQK2 through crystalline form modification. Four different kinds of crystal forms of PQQK2, as indicated by powder X-ray diffraction patterns, are successfully obtained by simply controlling the addition of different kinds of poor solvent. These crystal forms exhibit four distinct nano/microscale morphological features including plate-like, prismatic, and strip-like crystals with ultra-long and varying lengths. Notably, the water solubility of PQQK2 varies significantly depending on the specific crystal form and morphology, which influences the effective surface area exposed to the water. This study provides, for the first time, a rational crystal engineering approach for tuning the physicochemical properties of PQQK2, offering valuable guidance for its formulation into high-performance dietary supplements and pharmaceutical preparations.