Stability and in vivo Activity of Topical Corticosteroid Dilutions

Abstract

A stability-indicating assay for fluocinolone acetonide and fluocinonide was developed using high-performance liquid chromatography (HPLC). The degradation of fluocinonide resulted in a primary degradation product which was identified as fluocinolone acetonide. This is turn degraded to a series of unidentified products which had similar retention times to those produced when fluocinolone acetonide was used as the original steroid. The disappearance of both steroids followed first-order kinetics. The HPLC assay method was used to investigate the shelf-life of Synalar® ointment (fluocinolone acetonide 0.025% w/w) and Metosyn® cream (fluocinonide 0.05% w/w) diluted 1 in 4 and 1 in 10 in Lipobase® and Unguentum Merck®. In addition, Metosyn Diluent® was studied for that product. The formulations were stored at 4°C, 25°C and 32°C for a maximum of ten months. The 1 in 4 formulations of Synalar® showed no loss of steroid in the first four months of storage at 25°C. The 1 in 10 formulations were markedly less stable with shelf-lives of 1-2 months. The 1 in 4 formulations of Metosyn® were all stable for nine months at 25°C. The 1 in 10 formulations were stable over the seven months studied. Storage of the dilutions at 4°C can extend the shelf-life of the products. Elevation of temperature had no significant effect. The in vivo activity of extemporaneous formulations of Synalar® was compared to that of the undiluted steroid, the commercially available diluted product and the bases used by means of a vasoconstrictor assay. The blanching potency of the 1 in 4 dilutions was not significantly different to that of the undiluted steroid, p<0.05, and that of the 1 in 10 dilutions was not significantly different to that of the bases alone, p<0.05. The two groups were significantly different, p<0.05, although there was some overlap between the 1 in 4 dilutions and the 1 in 10 in Lipobase®. There was no linear relationship between dilution and potency, but the choice of base did have an effect on the potency of the formulation.