Effect of solution supersaturation on crystal formation of Vitamin K2 based on near infrared spectroscopy analysis technology

Abstract

Polymorphism is frequently encountered in most small molecule drugs and vitamin supplements, and the physical and chemical parameters of crystalline drugs may directly affect the solubility, bioavailability and clinical effects of the substances in the human body. Supersaturation is the key driving force of crystal nucleation and growth. Crystal forms and sizes are different under different supersaturation conditions. To rapid and efficient detection concentration of Vitamin K2, we established a solution concentration prediction model using near-infrared (NIR) spectroscopy in this study. The influence of supersaturation on Vitamin K2 crystal formation was explored. The results showed that for freezing crystallization, the supersaturation would be larger than evaporative crystallization and the size of the crystals would be smaller. The particle size of freezing crystallization is mainly in the range of 5–20 μm while the particle size of evaporative crystallization is mostly distributed in the range of 20–40 μm. This study also found that the crystal form obtained by solvent evaporation method was more regular, mostly in flake shape and smooth surface. These results have guiding significance for biological preparation of high-purity Vitamin K2 products with regular crystal shape, uniform particle size and good bioavailability.