AAPS PharmSciTech

, Volume 12, Issue 2, pp 610–619 | Cite as

A Kinetic Study of the Polymorphic Transformation of Nimodipine and Indomethacin during High Shear Granulation

  • Zhen Guo
  • Mingxin Ma
  • Tianyi Wang
  • Di Chang
  • Tongying Jiang
  • Siling Wang
Research Article


The objective of the present study was to investigate the mechanism, kinetics, and factors affecting the polymorphic transformation of nimodipine (NMD) and indomethacin (IMC) during high shear granulation. Granules containing active pharmaceutical ingredient, microcrystalline cellulose, and low-substituted hydroxypropylcellulose were prepared with ethanolic hydroxypropylcellulose solution, and the effects of independent process variables including impeller speed and granulating temperature were taken into consideration. Two polymorphs of the model drugs and granules were characterized by X-ray powder diffraction analysis and quantitatively determined by differential scanning calorimetry. A theoretical kinetic method of ten kinetic models was applied to analyze the polymorphic transformation of model drugs. The results obtained revealed that both the transformation of modification I to modification II of NMD and the transformation of the α form to the γ form of IMC followed a two-dimensional nuclei growth mechanism. The activation energy of transformation was calculated to be 7.933 and 56.09 kJ·mol−1 from Arrhenius plot, respectively. Both the granulating temperature and the impeller speed affected the transformation rate of the drugs and, in particular, the high shear stress significantly accelerated the transformation process. By analyzing the growth mechanisms of granules in high-shear mixer, it was concluded that the polymorphic transformation of NMD and IMC took place in accordance with granule growth in a high-shear mixer.


differential scanning calorimetry granule growth mechanism high shear granulation polymorphic transformation kinetic X-ray powder diffraction 



The authors would like to thank Collette N.V, Belgium, for supplying the MicroGral® high-shear mixers and for their logistic and technical support. This work was supported by the National Basic Research Program of China (973 Program; No.2009CB930300) and Major National Platform for Innovative Pharmaceuticals (No. 2009ZX09301-012).


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Copyright information

© American Association of Pharmaceutical Scientists 2011

Authors and Affiliations

  • Zhen Guo
    • 1
  • Mingxin Ma
    • 2
  • Tianyi Wang
    • 1
  • Di Chang
    • 1
  • Tongying Jiang
    • 1
  • Siling Wang
    • 1
  1. 1.School of PharmacyShenyang Pharmaceutical UniversityShenyangPeople’s Republic of China
  2. 2.Shenyang Xingqi Pharmaceutical Co. Ltd.ShenyangPeople’s Republic of China

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