Hydrotropic Antisolvent Crystallization for the Reduction in the Particle Size of Methylcobalamin

The active form of vitamin B12, methylcobalamin, is vital for normalizing neurological and hematological manifestations of B12 deficiency. Particle size reduction gives various advantages over larger particles, including increased surface area, improved biological activity, and greater penetration capacity, which could benefit medication. In the present study, hydrotropy and antisolvent crystallization have been combined to reduce the particle size of methylcobalamin along with the improved yield. Hansen solubility parameters (HSPs) have been utilized for selecting the solvent and antisolvent. For hydrotropic antisolvent crystallization (HAC), acetone, propan-1-ol, and resorcinol were selected as the antisolvent, solvent, and hydrotrope, respectively. Solubility enhancement by resorcinol and the effect of various parameters have been investigated. The three-level three-factor full factorial (FF) design has been employed to study the individual and interactive effects of the ratio of antisolvent to solvent (5–40 v/v), the rate of addition (5–20 mL/h), and methylcobalamin concentration (3–9.2 mg/mL) on particle size. The crystallized particles were characterized by various techniques to assess their structure, size, stability, and purity. The hydrotropic antisolvent crystallization has offered easy recovery of resorcinol and acetone. Finally, the greener aspects of the proposed method have been highlighted to showcase its sustainability