HPLC EVALUATION OF SOLVOLYSIS OF A NOVEL ESTER FLUOCINOLONE ACETONIDE 21-(2′-PHENOXYPROPIONATE) IN COMPARISON WITH FLUOCINONIDE

Abstract

In this study the solvolysis of novel fluocinolone acetonide 21-(2′-phenoxypropionate) in comparison with fluocinonide was analyzed in order to evaluate this process as an in vitro model for prodrug activation. The solvolysis was performed in ethanol:water (90:10 v/v) mixture using the excess of NaHCO₃. The solvolytic mixtures of those esters with different lipophilicity were assayed by proposed RP-HPLC method using isocratic elution with methanol:water (75:25 v/v); flow rate 1 mL min⁻¹, and detection at 238 nm. Solvolytic rate constants (at 25°C) for novel prodrug fluocinolone acetonide 21-(2′-phenoxypropionate) (0.0434 h⁻¹) and fluocinonide (0.0593 h⁻¹) have been compared. This in vitro model of solvolysis and corresponding rate constants are in good correlation with our preliminary data of anti-inflammatory potencies of those prodrugs. Limits of detection, important for the initial stage of solvolysis, were experimentally determined with values of 4.10 μM and 0.24 μM for fluocinolone acetonide 21-(2′-phenoxypropionate) and fluocinonide, respectively.

Keywords:

• fluocinolone acetonide esters
• fluocinonide
• prodrug
• RP-HPLC
• solvolysis
• solvolytic rate constants

ACKNOWLEDGMENTS

This work was partially supported by the Ministry of Education and Science, Belgrade, Serbia, as part of Project No. 172041.