The effect of drug concentration on the thermal (dark) degradation of promethazin hydrochloride in aqueous solution.

The thermal (dark) degradation of promethazine hydrochloride in aqueous solution presents a complex kinetic picture. The process is oxygen dependent and is modified by EDTA. In citrate buffer, pH 4.0, ionic strength 0.5M, containing 0.1% EDTA, the thermal degradation at 90 degrees can be fitted to first order rate plots at drug concentrations up to 1.56 x 10.27 (0.5%) and to zero order rate plots at drug concentrations greater than 9.35 x 10.2M (3.0%). At intermediate concentrations no simple equation can describe the data. These effects have been correlated with the formation of drug micelles and the rate date have been interpreted on the basis of a first order monomer process and a half order micellar process occurring simultaneously.