Temperature- and glass transition temperature-dependence of bimolecular reaction rates in lyophilized formulations described by the Adam-Gibbs-Vogel equation
✍ Scribed by Sumie Yoshioka; Yukio Aso; Shigeo Kojima
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- English
- Weight
- 119 KB
- Volume
- 93
- Category
- Article
- ISSN
- 0022-3549
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✦ Synopsis
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 (T g )-dependence was compared with that of structural relaxation time (t 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 T g , observed at various temperatures, exhibited a temperature dependence similar to that of t at temperatures below T g . Furthermore, the rates of acetyl transfer and the Maillard reaction in formulations containing a-glucose polymers and oligomers increased, as the T g of formulations decreased, either associated with decreases in molecular weight of excipient or with increases in water content. The observed T g dependence was similar to that of t in the range of T g higher than the experimental temperature. The results suggest a possibility that bimolecular reaction rate at temperatures below T g can be predicted from that observed at the T g 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.