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 .