Reduction in particle size of methylcobalamin using antisolvent crystallization

Abstract

Vitamin B12 is a vital water-soluble micronutrient required for maintaining the human health. However, one of the major encountered problems related to human health is a deficiency of vitamin B12 due to a strict vegetarian diet, malabsorption, pernicious anemia, surgical resection, etc. The deficiency of vitamin B12 can be overcome by taking vitamin supplements like methylcobalamin. Oral delivery of vitamin supplements is the most widely preferred route for administration as well as it gives good patient compliance. Particle size reduction of active ingredient enhances the dissolution rate which is very important in oral delivery. In the present study, methylcobalamin was re-crystallized using antisolvent crystallization technique and effect of various parameters like time (5–15 min), volume of solvent (0.5–1.5 mL), rate of addition (0.056–0.16 mL/min) and temperature (15–31 °C) on particle size was investigated. The aciculate shape of methylcobalamin was observed when re-crystallized using water as a solvent and acetone as an antisolvent. Increase in time from 5 min to 15 min increased the particle size (4.85 μm to 8.18 μm) while the increase in the volume of solvent from 0.5 mL to 1.5 mL has decreased the particle size (8.18 μm to 5.32 μm) and less effect was observed on particle size with a decrease in temperature (31 °C to 15 °C). The maximum impact on particle size (8.18 μm to 3.21 μm) was observed with the rate of addition from 0.16 mL/min to 0.056 mL/min. For water-acetone system, the particle size of methylcobalamin was found to decrease from 40.5 µm to 2.37 µm at 31 °C, 10 mL antisolvent, 0.5 mL solvent, 0.067 mL/min and 15 min. Hence, ∼18 times reduction in particle size was observed using antisolvent crystallization.