Thermodynamics Research Today is a free monthly online journal that collates and summarizes the latest research about Thermodynamics, including details on enthalpy, entropy, energy transitions.

Molecular Mobility, Thermodynamics and Stability of Griseofulvin's Ultraviscous and Glassy States from Dynamic Heat Capacity.

Tombari E, Presto S, Johari GP, Shanker RM

Istituto per i Processi Chimico-Fisici del CNR, 56124, Pisa, Italy.

PURPOSE: To determine the calorimetric relaxation time needed for modeling griseofulvin's stability against crystallization during storage. METHODS: Both temperature-modulated and unmodulated scanning calorimetry have been used to determine the heat capacity of griseofulvin in the glassy and melt state. RESULTS: The calorimetric relaxation time, tau ( cal ), of its melt varies with the temperature T according to the relation, [Formula: see text], and the distribution of relaxation times parameter is 0.67. The unrelaxed heat capacity of the griseofulvin melt is equal to its vibrational heat capacity. CONCLUSIONS: Griseofulvin neither crystallizes on heating to 373 K at 1 K/h rate, nor on cooling. Molecular mobility and vibrational heat capacity measured here are more reliable for modeling a pharmaceutical's stability against crystallization than the currently used kinetics-thermodynamics relations, and molecular mobility in the (fixed structure) glassy state is much greater than the usual extrapolation from the melt state yields. Molecular relaxation time of the glassy state of griseofulvin is about 2 months at 298 K, and longer at lower temperatures. It would spontaneously increase with time. If the long-range motions alone were needed for crystallization, griseofulvin would become more stable against crystallization during storage.

Published 3 April 2008 in Pharm Res, 25(4): 902-12.
Full-text of this article is available online (may require subscription).

© 2005-2008 Thermodynamics Research Today. All Rights Reserved.