title: Fast surface crystallization of amorphous griseofulvin below T g.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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 degrees C (T (g)-48 degrees C) and room temperature (T (g)-66 degrees C) was monitored using XRPD.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, Wisconsin 53706, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhu
authors.forename: Janan
authors.initials: J
authors.lastname: Jona
authors.forename: Karthik
authors.initials: K
authors.lastname: Nagapudi
authors.forename: Tian
authors.initials: T
authors.lastname: Wu
mesh_terms: D002152:Calorimetry, Differential Scanning; D018360:Crystallography, X-Ray; D004355:Drug Stability; D005898:Glass / Q000737:chemistry*; D006046:Gold / Q000737:chemistry; D006118:Griseofulvin / Q000737:chemistry*; D015394:Molecular Structure; D010316:Particle Size; D011208:Powders; D013499:Surface Properties; D044366:Transition Temperature; D014961:X-Ray Diffraction
chemical_list: D011208:Powders; D006118:Griseofulvin; D006046:Gold