Thermodynamics, Molecular Mobility and Crystallization Kinetics of Amorphous Griseofulvin

Deliang Zhou†, Geoff G. Z. Zhang†, Devalina Law‡, David J. W. Grant§ and Eric A. Schmitt*†
Global Pharmaceutical R&D, and Global Pharmaceutical Operations, Abbott Laboratories, and Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Weaver-Densford Hall, 308 Harvard Street SE, Minneapolis, Minnesota 55455-0343
Mol. Pharmaceutics, 2008, 5 (6), pp 927–936
DOI: 10.1021/mp800169g
Publication Date (Web): November 5, 2008
Copyright © 2008 American Chemical Society
†

Global Pharmaceutical R&D, Abbott Laboratories.

,
‡

Global Pharmaceutical Operations, Abbott Laboratories.

,
§

University of Minnesota.

,
* Author to whom correspondence should be addressed. Mailing address: Abbott Laboratories, 1401 Sheridan Road, Dept. R4P7, Bldg. M3B, North Chicago, IL 60064-6246. Tel: (847) 938-4835. Fax: (847) 937-8918. E-mail: eric.a.schmitt@abbott.com.
This article is part of the Amorphous Pharmaceutical Solids special issue.

Abstract

Abstract Image

Griseofulvin is a small rigid molecule that shows relatively high molecular mobility and small configurational entropy in the amorphous phase and tends to readily crystallize from both rubbery and glassy states. This work examines the crystallization kinetics and mechanism of amorphous griseofulvin and the quantitative correlation between the rate of crystallization and molecular mobility above and below Tg. Amorphous griseofulvin was prepared by rapidly quenching the melt in liquid N2. The thermodynamics and dynamics of amorphous phase were then characterized using a combination of thermal analysis techniques. After characterization of the amorphous phase, crystallization kinetics above Tg were monitored by isothermal differential scanning calorimetry (DSC). Transformation curves for crystallization fit a second-order John−Mehl−Avrami (JMA) model. Crystallization kinetics below Tg were monitored by powder X-ray diffraction and fit to the second-order JMA model. Activation energies for crystallization were markedly different above and below Tg suggesting a change in mechanism. In both cases molecular mobility appeared to be partially involved in the rate-limiting step for crystallization, but the extent of correlation between the rate of crystallization and molecular mobility was different above and below Tg. A lower extent of correlation below Tg was observed which does not appear to be explained by the molecular mobility alone and the diminishing activation energy for crystallization suggests a change in the mechanism of crystallization.

View: Full Text HTML | Hi-Res PDF | PDF w/ Links

Tools

History

  • Published In Issue December 01, 2008
  • Article ASAPNovember 06, 2008
  • Received: September 16, 2008
    Accepted: October 14, 2008
    Revised: October 13, 2008

Recommend & Share

Related Content

Other ACS content by these authors: