Effect of application time of betamethasone-17-valerate 0.1% cream on skin blanching and stratum corneum drug concentration

Abstract

The effect of application time on skin blanching response and stratum corneum concentration after topical application of 0.1% betamethasone-17-valerate cream on healthy volunteers was assessed. Total corticosteroid content in the stratum corneum (SC) was determined at different application times (0.5, 8, 10 and 24 h) from five subjects in whom blanching was also evaluated at the same application times by visual score, colorimetry ( L-, a- and b-values) and Laser Doppler flowmetry. No significant differences between corticosteroid concentration in the SC at 8, 10 and 24 h was observed when compared using ANOVA and t-test ( P > 0.05) while drug content at 0.5 h was significantly lower ( P < 0.05). Significant differences between the blanching response at 0.5 h and the other time points (8, 10 and 24 h) were observed by visual assessment and a-value readings from a chromameter. However, at 24 h visual score and †a- values were lower than those measured at 8 and 10 h. but this difference was significant only for †a- values . This findings suggest that skin blanching may not be related to drug concentration in the stratum corneum and that †a- readings may be more sensitive and accurate than visual score in evaluating skin blanching. L-values were not significantly different at all the time points while b-values at 0.5 h were significantly different only from those at 8 and 10 h. Skin blanching was not observed when laser Doppler flow was measured while the concentration parameter was capable of detecting blanching; however, the concentration values were not significantly different at all the application times. The results of this study suggest that the duration of application should be carefully chosen to assess betamethasone-17- valerate topical bioavailability since after long application time skin blanching response may not be related to drug concentration in the stratum corneum.