Kinetics of decomposition and formulation of hydrocortisone butyrate in semiaqueous and gel systems.

The stability of hydrocortisone butyrate in semiaqueous and formulated gel systems has been investigated. It was shown that hydrocortisone butyrate underwent reversible isomerization to the C-21 ester of butyric acid. This ester then hydrolyzed to hydrocortisone, which in turn degraded to a complex mixture of compounds. This step is metal catalyzed and can be inhibited by the addition of EDTA [disodium(ethylenedinitrilo)tetraacetate]. The kinetics of decomposition is modeled using nonlinear regression analysis, and the rate constants for the various decomposition pathways are quantified.