Effect of heating rate and kinetic model selection on activation energy of nonisothermal crystallization of amorphous felodipine

Sayantan Chattoraj, Chandan Bhugra, Zheng Jane Li, Changquan Calvin Sun

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

The nonisothermal crystallization kinetics of amorphous materials is routinely analyzed by statistically fitting the crystallization data to kinetic models. In this work, we systematically evaluate how the model-dependent crystallization kinetics is impacted by variations in the heating rate and the selection of the kinetic model, two key factors that can lead to significant differences in the crystallization activation energy (Ea) of an amorphous material. Using amorphous felodipine, we show that the Ea decreases with increase in the heating rate, irrespective of the kinetic model evaluated in this work. The model that best describes the crystallization phenomenon cannot be identified readily through the statistical fitting approach because several kinetic models yield comparable R2. Here, we propose an alternate paired model-fitting model-free (PMFMF) approach for identifying the most suitable kinetic model, where Ea obtained from model-dependent kinetics is compared with those obtained from model-free kinetics. The most suitable kinetic model is identified as the one that yields Ea values comparable with the model-free kinetics. Through this PMFMF approach, nucleation and growth is identified as the main mechanism that controls the crystallization kinetics of felodipine. Using this PMFMF approach, we further demonstrate that crystallization mechanism from amorphous phase varies with heating rate.

Original languageEnglish (US)
Pages (from-to)3950-3957
Number of pages8
JournalJournal of Pharmaceutical Sciences
Volume103
Issue number12
DOIs
StatePublished - Dec 2014

Bibliographical note

Funding Information:
Financial support for this work was provided by Boehringer-Ingelheim Pharmaceuticals Inc., USA. S.C. thanks the University of Minnesota for a Doctoral Dissertation Fellowship and a David and Marilyn Grant Fellowship in Pharmaceutics.

Keywords

  • Activation energy
  • Amorphous
  • Calorimetry (DSC)
  • Crystallization
  • Heating rate
  • Kinetics
  • Nonisothermal
  • Physical stability
  • Thermal analysis

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