Antisolvent Crystallization for the Size Reduction of Cholecalciferol: Parametric and Optimization Study

The active form of vitamin D₃, cholecalciferol, is one of the essential constituents that allows most cells to develop and differentiate, and also critical for parathyroid regulation and immune system improvement. Reducing the size of cholecalciferol can offer several benefits, such as improved surface area, enhanced biological activity, and better penetrating power. In this context, antisolvent crystallization is utilized to decrease the particle size of cholecalciferol. The solvent and antisolvent selections are made using Hansen solubility parameters (HSP). The effect of various factors like ratio of antisolvent to solvent (1:1–20:1, v/v), rate of addition (5–40, mL h⁻¹), stirring speed (200–500 rpm), concentration of cholecalciferol (2.5–15, mg mL⁻¹), and temperature (15–30 °C) is assessed using parametric study. The individual and interaction effects are studied using the central composite design (CCD) followed by model formulation and optimization. The lowest particle size (111.6 nm) is obtained at 2.5 mg mL⁻¹ concentration of cholecalciferol, 25 mL h⁻¹ rate of addition, 10:1 (v/v) antisolvent to solvent ratio, 20 °C temperature, and stirring speed of 300 rpm.