Pharmaceutical Research

, Volume 27, Issue 8, pp 1558–1567 | Cite as

Fast Surface Crystallization of Amorphous Griseofulvin Below T g

  • Lei Zhu
  • Janan Jona
  • Karthik Nagapudi
  • Tian Wu
Research Paper



To study crystal growth rates of amorphous griseofulvin (GSF) below its glass transition temperature (T g) and the effect of surface crystallization on the overall crystallization kinetics of amorphous GSF.


Amorphous GSF was generated by melt quenching. Surface and bulk crystal growth rates were determined using polarized light microscope. X-ray powder diffraction (XRPD) and Raman microscopy were used to identify the polymorph of the crystals. Crystallization kinetics of amorphous GSF powder stored at 40°C (T g−48°C) and room temperature (T g−66°C) was monitored using XRPD.


Crystal growth at the surface of amorphous GSF is 10- to 100-fold faster than that in the bulk. The surface crystal growth can be suppressed by an ultrathin gold coating. Below T g, the crystallization of amorphous GSF powder was biphasic with a rapid initial crystallization stage dominated by the surface crystallization and a slow or suspended late stage controlled by the bulk crystallization.


GSF exhibits the fastest surface crystallization kinetics among the known amorphous pharmaceutical solids. Well below T g, surface crystallization dominated the overall crystallization kinetics of amorphous GSF powder. Thus, surface crystallization should be distinguished from bulk crystallization in studying, modeling and controlling the crystallization of amorphous solids.


amorphous solids coating crystallization kinetic griseofulvin surface-enhanced crystallization 



The work is supported by Amgen summer internship program. We thank Dr.Yuan-hon Kiang, Dr. Darren Reid in Amgen and Professor Lian Yu in University of Wisconsin—Madison for helpful discussions and valuable comments.


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of ChemistryUniversity of Wisconsin—MadisonMadisonUSA
  2. 2.Small Molecule Process and Product DevelopmentAmgen Inc.Thousand OaksUSA

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