Temperature- and glass transition temperature-dependence of bimolecular reaction rates in lyophilized formulations described by the Adam-Gibbs-Vogel equation.
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 (tau 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 tau at temperatures below Tg. Furthermore, the rates of acetyl transfer and the Maillard reaction in formulations containing alpha-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 tau 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.
National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan. yoshioka@nihs.go.jp
Sumie
S
Yoshioka
Yukio
Y
Aso
Shigeo
S
Kojima
D000465:Algorithms; D001241:Aspirin / Q000737:chemistry; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D003911:Dextrans / Q000737:chemistry; D005079:Excipients; D005612:Freeze Drying; D006813:Humidity; D006863:Hydrogen-Ion Concentration; D007534:Isomaltose / Q000737:chemistry; D007700:Kinetics; D008970:Molecular Weight; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry; D013411:Sulfadiazine / Q000737:chemistry; D013696:Temperature
D003911:Dextrans; D005079:Excipients; D004364:Pharmaceutical Preparations; D013411:Sulfadiazine; D007534:Isomaltose; D011205:Povidone; D001241:Aspirin