Stability of fludrocortisone acetate solutions prepared from tablets and powder

Abstract

To assess the stability of fludrocortisone acetate oral solutions prepared from tablets and powder at three temperatures over a 60-days period. Solutions of fludrocortisone acetate 40 μg/ml were prepared from commercially available 0.05-mg tablets and powder in ethanol 17% v/v. They stored in an amber glass prescription bottles at +4, +23 and +40°C shielded from light. The concentrations of fludrocortisone acetate were determined in duplicate by high-performance liquid chromatography at 0, 1, 7, 14, 30, 50 and 60 days. The initial and final pH of solutions were compared. The recovery of fludrocortisone acetate from tablets was determined. The times (t 90) needed for fludrocortisone acetate to fall to 90% of it's initial concentration were calculated by a linear regression analysis to allow the determination of the expired dates. The recovery of fludrocortisone acetate from tablets was 78±3%. The t 90 expressed with 95% confidence limits were 2±1 and 22±3 days for the solutions prepared from tablets and stored at +23 and +4°C, respectively, whereas t 90 were 11±2 days and at least 60 days for the solutions prepared with the powder and stored at +23 and +4°C, respectively. No color or odour changes were observed during the study period. The initial pH of the solutions prepared from tablets and powder were 7.7 and 6.9, respectively. No change of pH values was observed at the end of the 60 days. Significant degradation of fludrocortisone acetate occurred in formulations stored at +23°C. Fludrocortisone acetate 40 μg/ml solutions prepared from tablets and powder were stable 19 days and at least 60 days, respectively, when stored at +4°C. The solution prepared from powder is the best in term of stability and final concentration which is independent on the fludrocortisone acetate recovery.