Isothermal and Nonisothermal Decomposition of Thymopentin and Its Analogs in Aqueous Solution

Abstract

Purpose. The degradation kinetics of thymopentin (RKDVY) and its analogs (RKDVW and RPDVY) in aqueous solution was studied by isothermal and nonisothermal methods.

Methods. The isothermal decomposition of thymopentin and its analogs was investigated as a function of pH (2−10), temperature (37, 57, and 80°C) and ionic strength (μ = 0.02 to 1). Nonisothermal decomposition studies were performed using a linear temperature programmer. The temperature increasing rate was set to 0.25°C per hour and the temperature interval varied from 40 to 88°C.

Results. The decomposition of thymopentin and its analogs followed first order kinetics. The dependence of the rate constant on temperature followed a linear Arrhenius plot. This indicated that the degradation mechanism of thymopentin and its analogs might be the same within the temperature range studied. The energies of activation were found to be in close agreement for the isothermal and nonisothermal studies, suggesting that the nonisothermal studies may save considerable amount of time in the early stages of drug development. The logK-pH profile of thymopentin suggests that maximum stability is achieved in the pH range of 6−8.

Conclusions. These results indicate that the nonisothermal methodology provides an attractive alternative to isothermal methods, as it requires a much lower amount of both material and time, to determine the peptide stability and to estimate the shelf-life for peptide pharmaceutical preparations.