Investigation of solution and vapor phase mediated phase transformation in thiamine hydrochloride

Paroma Chakravarty, Ramprakash Govindarajan, Raj Suryanarayanan

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12 Scopus citations


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 ∼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 (408C/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.

Original languageEnglish (US)
Pages (from-to)3941-3952
Number of pages12
JournalJournal of Pharmaceutical Sciences
Issue number9
StatePublished - Sep 2010

Bibliographical note

Funding Information:
The fluid-bed granulation work was carried out at Eli Lilly and Company during PC’s summer internship. We thank Gregory Clanton for acquiring the X-ray diffractometry data and Edward McCarty for assistance with fluid-bed granulation. Dr. Gregory Stephenson, Dr. David Moeckly, and Dr. Leslie King are gratefully acknowledged for their support. Partial financial support for this project was received from Dane O. Kildsig Center for Pharmaceutical Processing Research. Paroma Chakravarty is the recipient of the Doctoral Dissertation Fellowship from the Graduate School, University of Minnesota. Part of this work was carried out in the I.T. Characterization facility of the University of Minnesota which receives partial support from NSF through the NNIN program.


  • Excipients
  • Hydrates
  • Physical stability
  • Water sorption
  • X-ray powder diffractometry


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