Is the Skin Absorption of Hydrocortisone Modified by the Variability in Dosing Topical Products?

Fingertip units have been proposed as a tool to standardize topical therapy with semisolid formulations. However, no studies to date have characterized the variability in dosing by patients using this concept and whether this variability ultimately affects the topical absorption of drugs. This work aimed to answer these two questions. A first study determined the dose measured, the area of spread and the area-normalized dose for a 1% hydrocortisone cream and ointment applied by members of the public using this dosing approach before and after brief counselling. Then, in vivo tape-stripping and in vitro permeation studies investigated whether the variability in the area-normalized dose altered the skin absorption of hydrocortisone. Participants applied greater doses and spread them over larger areas after a short counselling intervention leading to smaller area-normalized doses. In vivo hydrocortisone uptake by the stratum corneum was significantly greater for the higher normalized dose and the differences were further supported by the in vitro permeation studies. However, these differences were relatively small and not proportional to the increase in normalized dose. This work shows that, following brief advice, patients and carers can apply consistent and sufficient doses of corticosteroids whilst minimizing risks and variability in hydrocortisone absorption.