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

Bimolecular reaction rates in lyophilized aspirin-sulfadiazine formulations containing poly(vinylpyrrolidone)(PVP), dextran and isomalto-oligomers of different molecular weights were determined in the presence of various water contents, and their temperature- and T_g-dependence was compared with that of structural relaxation time (t) calculated according to the Adam-Gibbs-Vogel (AGV) 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 PVP 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.

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