Crystallization behavior of mannitol in frozen aqueous solutions

Raghu K. Cavatur, N. Murti Vemuri, Abira Pyne, Zofia Chrzan, David Toledo-Velasquez, Raj Suryanarayanan

Research output: Contribution to journalArticlepeer-review

101 Scopus citations


Purpose. To study the effect of cooling rate, the influence of phosphate buffers and polyvinylpyrrolidone (PVP) on the crystallization behavior of mannitol in frozen aqueous solutions. Methods. Low-temperature differential scanning calorimetry and powder X-ray diffractometry were used to characterize the frozen solutions. Results. Rapid cooling (20°C/min) inhibited mannitol crystallization, whereas at slower cooling rates (10°C and 5°C/min) partial crystallization was observed. The amorphous freeze-concentrate was characterized by two glass transitions at -32°C and -25°C. When the frozen solutions were heated past the two glass transition temperatures, the solute crystallized as mannitol hydrate. An increase in the concentration of PVP increased the induction time for the crystallization of mannitol hydrate. At concentrations of ≥100 mM, the buffer salts significantly inhibited mannitol crystallization. Conclusions. The crystallization behavior of mannitol in frozen solutions was influenced by the cooling rate and the presence of phosphate buffers and PVP.

Original languageEnglish (US)
Pages (from-to)894-900
Number of pages7
JournalPharmaceutical research
Issue number6
StatePublished - 2002


  • Differential scanning calorimetry
  • Frozen
  • Mannitol
  • X-ray powder diffractometry


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