Kinetics of degradation of a cyclic lactam analog of α-melanotropin (MT-II) in aqueous solution

The kinetics of degradation of MT-II in aqueous buffered solution was studied in order to facilitate the formulation of a stable oral dosage form. A stability-indicating high-performance liquid Chromatographic (HPLC) assay was used to measure the concentrations of MT-II remaining at various time periods. The rate of degradation of MT-II was studied as a function of pH, phosphate buffer concentration, temperature and ionic strength. Results indicated that the degradation of MT-II followed apparent first-order kinetics. The pH-rate profile showed that MT-II was most stable at approximately pH 5.0. Data obtained from this study also indicated that the degradation rate of this peptide was directly proportional to phosphate buffer concentration and temperature. The shelf-life of MT-II in aqueous buffer solutions at 25°C was 27 h. The activation energy was 7.5 kcal/mol. The degradation rate of MT-II appeared to be independent of the ionic strength of the aqueous buffered solution.