Investigation of solution and vapor phase mediated phase transformation in thiamine hydrochloride.
Thiamine 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 approximately 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 degrees C/75% RH). Based on Raman spectroscopy (40 degrees 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, approximately 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.
Chakravarty
Paroma
P
Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Govindarajan
Ramprakash
R
Suryanarayanan
Raj
R
D002482:Cellulose / Q000737:chemistry; D044367:Phase Transition; D033362:Powder Diffraction; D012995:Solubility; D013831:Thiamine / Q000737:chemistry*; D014867:Water / Q000737:chemistry*; D014961:X-Ray Diffraction
D014867:Water; D002482:Cellulose; C109691:microcrystalline cellulose; D013831:Thiamine