Temperature- and glass transition temperature-dependence of bimolecular reaction rates in lyophilized formulations described by the Adam-Gibbs-Vogel equation

Temperature- and glass transition temperature-dependence of bimolecular reaction rates in lyophilized formulations described by the Adam-Gibbs-Vogel equation
February 2004
Sumie Yoshioka, Yukio Aso, Shigeo Kojima, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan
Journal of Pharmaceutical Sciences, Volume 93, Issue 4 , Pages 1062 - 1069
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Abstract
Bimolecular reaction rates in lyophilized aspirin-sulfadiazine formulations containing poly(vinylpyrrolidone), dextran, and isomalto-oligomers of different molecular weights were determined in the presence of various water contents, and their temperature- and glass transition temperature (Tg)-dependence was compared with that of structural relaxation time ( calculated according to the Adam-Gibbs-Vogel equation, in order to understand how chemical degradation rates of drugs in lyophilized formulations are affected by molecular mobility. The rate of acetyl transfer in poly(vinylpyrrolidone) K30 and dextran 40k formulations with a constant Tg, observed at various temperatures, exhibited a temperature dependence similar to that of at temperatures below Tg. Furthermore, the rates of acetyl transfer and the Maillard reaction in formulations containing -glucose polymers and oligomers increased, as the Tg of formulations decreased, either associated with decreases in molecular weight of excipient or with increases in water content. The observed Tg dependence was similar to that of in the range of Tg higher than the experimental temperature. The results suggest a possibility that bimolecular reaction rate at temperatures below Tg can be predicted from that observed at the Tg on the basis of temperature dependence of structural relaxation time in amorphous systems, if the degradation rate is proportional to the diffusion rate of reacting compounds. ? 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93: 1062-1069, 2004
Keywords
acetyl transfer ? lyophilized formulation ? glass transition temperature ? molecular mobility