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Investigation of Solution and Vapor Phase Mediated Phase Transformation in Thiamine Hydrochloride
Journal article   Peer reviewed

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

Paroma CHAKRAVARTY, Ramprakash GOVINDARAJAN and Raj SURYANARAYANAN
Journal of pharmaceutical sciences, Vol.99(9), pp.3941-3952
2010
DOI: 10.1002/jps.22240
PMID: 20575002

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Abstract

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.
Pharmaceutical technology. Pharmaceutical industry Biological and medical sciences Medical sciences General pharmacology Pharmacology. Drug treatments

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