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.

Date of Award	Sept 1992
Original language	English
Awarding Institution	Aston University