Thermodynamics, molecular mobility and crystallization kinetics of amorphous griseofulvin.
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.
Global Pharmaceutical R&D, Abbott Laboratories, USA.
Deliang
D
Zhou
Geoff G Z
GG
Zhang
Devalina
D
Law
David J W
DJ
Grant
Eric A
EA
Schmitt
D000935:Antifungal Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D004355:Drug Stability; D005898:Glass / Q000737:chemistry; D006118:Griseofulvin / Q000737:chemistry*; D006361:Heating; D007700:Kinetics; D015394:Molecular Structure; D009038:Motion; D013816:Thermodynamics; D044366:Transition Temperature
D000935:Antifungal Agents; D006118:Griseofulvin