완충 수용액중 로이신엔케팔린 및 [D-알라2]-로이신엔케팔린아미드의 물리화학적 안정성

Physicochemical Stability of Leucine Enkephalin and [D-Ala2]-Leucine Enkephalinamide in Buffered Aqueous Solution

To evaluate the feasibility of transmucosal delivery of leucine enkephalin (Leu-Enk) and its synthetic analog, [D-ala2]-leucine enkephalinamide (YAGFL), their physicochemical stabilities in aqueous buffered solutions were first investigated using a stability indicating high performance liquid chromatography. The degradation of Leu-Enk and YAGFL followed the pseudo-first-order kinetics. From the pH-rate profiles, it was found that the maximal stability of the two pentapeptides was at the pH of about 5.0. The shelf lives (t90%) for the degradation of Leu-Enk and YAGFL at pH 5.0 and 40oC were found to be 48.13 and 50.9 days, respectively. From the temperature dependence of the degradation, activation energies for Leu-Enk and YAGFL were calculated to be 13.61 and 13.47kcal/mole, respectively. A higher ionic strength and a higher initial peptide concentration in buffered solution slowed the degradation of the two pentapeptides. The addition of 2-hydroxypropyl-beta-cyclodextrin into the peptide solution did not affect the stability significantly.