Kinetics of thermal degradation of betamethasone valerate and betamethasone dipropionate in different media

Abstract

The effect of pH, media, phosphate concentration and ionic strength on the kinetics of thermal degradation of betamethasone valerate and betamethasone dipropionate has been investigated. A validated HPLC method has been used to determine the parent compounds and their major thermal degradation products identified in the reaction. Betamethasone-17-valerate gave rise to two major products, namely, betamethasone-21-valerate and betamethasone alcohol, and betamethasone dipropionate degraded into three major products, namely, betamethasone-17-propionate, betamethasone-21-propionate and betamethasone alcohol, in different media. Betamethasone valerate showed maximum stability at pH 4-5 while betamethasone dipropionate was maximally stable at pH 3.5-4.5. The degradation of betamethasone valerate and betamethasone dipropionate was found to follow first-order kinetics and the apparent first-order rate constants (kobs) for thermal degradation in different media range from 0.399-9.07×10-3 h-1 and 0.239-1.87×10-3 h-1, respectively. The values of the rate constants decrease with increasing solvent polarity, phosphate concentration and ionic strength. The second-order rate constants (k΄) for the phosphate ion inhibited reactions lie in the range of 3.02-1.30×10-6 M-1 s-1.