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Abstract

We investigated the degradation of fluocinolone acetonide (FA) incorporated into an oil-in-water cream base. The study examined the influence of temperature (23 to 80 degrees C) and cream pH (pH 2.3 to 6) on FA degradation rates. FA degradation followed pseudo-first-order kinetics and adhered to the Arrhenius expression over the entire temperature range investigated. At all temperatures, the pH strongly influenced the observed degradation rate constant (kobs) values, with rate minima observed near pH 4. The FA log(degradation rate)-pH profiles were consistent with a reaction mechanism requiring drug hydrolysis catalyzed by hydroxide and hydrogen ions. Taking into account both the temperature and the pH dependence of FA degradation permits calculating kobs values from the following equation: kobs = exp[22.5 - (17,200/RT)] + exp[38.7 - (22,200/RT)] x [H+] + exp[49.5 - (21,100/RT)] x [OH-] where the three bracketed terms represent Arrhenius expressions for neutral, acid-catalyzed, and base-catalyzed hydrolysis reactions. FA degradation in the cream base parallels the degradation of a related steroid (triamcinolone acetonide) in an aqueous alcohol solution. The equivalence between FA and triamcinolone acetonide kinetics in the different reaction media suggests that in the cream base, FA degradation is limited to an aqueous phase largely unperturbed by the presence of nonaqueous constituents that comprise the cream formulation.

Stability-indicating chromatographic determination of hydroquinone in combination with tretinoin and fluocinolone acetonide in pharmaceutical formulations with a photodegradation kinetic study

“…The manufacturer HPLC method determined HQ, FLA and the preservatives MET and PRP in one run but another HPLC method was used for determining TRT. The reported methods on FLA [10][11][12] did not mention its photodegradation pathway.…”

“…2 Two HPLC methods were reported for the determination of HQ in combination with TRT and FLA. 3,4 Many HPLC methods were published for studying the stability of TRT or FLA in single forms. [5][6][7][8][9][10][11][12][13][14] Kinetic studies were performed on tretinoin photodegradation. 6,9 A high performance thin layer chromatographic method was reported as a stability indicating determination of single HQ in pharmaceutical formulations.…”

Development of fluocinolone acetonide microemulsion mouthwash

“…The degradation rate constant was observed minimum at pH 4. In addition, FA degradation occurred in aqueous phase of the oil-in-water cream samples (Kenley et al, 1987). Therefore possibility of FA degradation might increase when it was surrounded by aqueous medium.…”

“…Degradation pathways of FA are oxidation, hydrolysis with pH dependence and photolysis. Degradation of FA is catalyze by hydrogen ion, hydroxide ion and trace metal ions (Kenley et al, 1987;Miolo et al, 2005). FA has been prepared in cream, gel, solution, and ointment dosage forms for topical use.…”