Phase transformation in thiamine hydrochloride tablets: Influence on tablet microstructure, physical properties, and performance

Paroma Chakravarty, Raj Suryanarayanan, Ramprakash Govindarajan

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


The objective of this article was to monitor phase transformation in thiamine hydrochloride, from a nonstoichiometric hydrate (NSH) to a hemihydrate (HH), in stored tablets, prepared both by direct compression and wet granulation, and to relate the storage-induced phase transformation with changes in tablet microstructure, physical properties, and performance. Raman spectroscopy revealed complete NSH → HH transformation in tablets, within 30 h of storage at 40°C/75% relative humidity. When the tablets were prepared by wet granulation of NSH alone, there was a marked increase in both tablet volume and hardness on storage. However, when microcrystalline cellulose (MCC) was included in granulation, the resulting stored tablets also exhibited a pronounced increase in disintegration time. In contrast, tablets prepared by dry processing via compression of a NSH-MCC physical mixture did not exhibit any changes in properties, despite the in situ solid form conversion. Scanning electron microscopy revealed growth of needle-like HH crystals in all stored tablets and mercury porosimetry revealed considerable changes in the pore size distribution during storage. Longer storage led to crystal growth (Ostwald ripening), causing further gradual but less dramatic changes in properties. The phase transformation and the complex interparticulate associations in the tablet influenced the changes in tablet microstructure, compact physical properties, and product behavior.

Original languageEnglish (US)
Pages (from-to)1410-1422
Number of pages13
JournalJournal of Pharmaceutical Sciences
Issue number4
StatePublished - Apr 2012

Bibliographical note

Funding Information:
We thank Yushi Feng, Ph.D., Edward McCarty, David Moeckly, Ph.D., and Leslie King, Ph.D., all from Eli Lilly and Company, for their help. 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.


  • Crushing strength
  • Crystals
  • Hydrate
  • Microscopy
  • Microstructure
  • Phase transition
  • Porosity
  • Preformulation
  • Raman spectroscopy
  • Solid state
  • Tablet


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