Investigation of Solution and Vapor Phase Mediated Phase Transformation in Thiamine Hydrochloride

ABSTRACTThiamine hydrochloride (THCl) can exist as an anhydrate (AH), a hemihydrate (HH) and as a nonstoichiometric hydrate (NSH) where the water content can range between 0 and ~1 mole of water per mole of THCl. We have investigated the NSH → HH phase transformation, in the presence of microcrystalline cellulose (MCC), following (i) wet massing, (ii) fluid- bed granulation, and (iii) exposure to water vapor (40°C/75% RH). Based on Raman spectroscopy (40°C), wet massing of NSH alone caused near complete transformation to HH in < 100 min. In the presence of MCC, the transformation rate was decelerated. During fluid-bed granulation, ~20% of NSH was transformed to HH and the deceleratory effect of MCC was much less pronounced. Exposure to water vapor, of both NSH-MCC powder blends and granules (prepared by fluid-bed) resulted in complete HH formation within 6 days. Presence of MCC in the powder blend did not affect HH formation kinetics, but facilitated phase transformation in the granules. NSH → HH conversion appeared to follow two-dimensional nucleation and growth model in powder blends, whereas the granules showed either three-dimensional diffusion controlled or a first-order kinetics. In a wet mass, polyvinyl pyrrolidone, a widely used binder, was much more effective than MCC in inhibiting HH formation during wet massing. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:3941–3952, 2010