Mechanism of amorphous itraconazole stabilization in polymer solid dispersions: Role of molecular mobility

Sunny P. Bhardwaj, Kapildev K. Arora, Elizabeth Kwong, Allen Templeton, Sophie Dorothee Clas, Raj Suryanarayanan

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Physical instability of amorphous solid dispersions can be a major impediment to their widespread use. We characterized the molecular mobility in amorphous solid dispersions of itraconazole (ITZ) with each polyvinylpyrroli-done (PVP) and hydroxypropylmethylcellulose acetate succinate (HPMCAS) with the goal of investigating the correlation between molecular mobility and physical stability. Dielectric spectra showed two mobility modes: α-relaxation at temperatures above the glass transition temperature (Tg) and β-relaxation in the sub-Tg range. HPMCAS substantially increased the α-relaxation time, with an attendant increase in crystallization onset time and a decrease in crystallization rate constant, demonstrating the correlation between α-relaxation and stability. The inhibitory effect on α-relaxation as well as stability was temperature dependent and diminished as the temperature was increased above Tg. PVP, on the other hand, affected neither the α-relaxation time nor the crystallization onset time, further establishing the link between α-relaxation and crystallization onset in solid dispersions. However, it inhibited the crystallization rate, an effect attributed to factors other than mobility. Interestingly, both of the polymers acted as plasticizers of β-relaxation, ruling out the latter's involvement in physical stability.

Original languageEnglish (US)
Pages (from-to)4228-4237
Number of pages10
JournalMolecular pharmaceutics
Issue number11
StatePublished - Jan 1 2014


  • Crystallization kinetics
  • Crystallization onset
  • Dielectric spectroscopy
  • Itraconazole
  • Molecular mobility
  • PVP
  • Solid dispersion
  • Synchrotron radiation

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