posted on 2021-06-14, 14:09authored byAndrea Pensado, Laura Hattam, K. A. Jane White, Anita McGrogan, Annette L. Bunge, Richard H. Guy, M. Begoña Delgado-Charro
Prediction
of skin absorption and local bioavailability from topical
formulations remains a difficult task. An important challenge in forecasting
topical bioavailability is the limited information available about
local and systemic drug concentrations post application of topical
drug products. Commercially available transdermal patches, such as
Scopoderm (Novartis Consumer Health UK), offer an opportunity to test
these experimental approaches as systemic pharmacokinetic data are
available with which to validate a predictive model. The long-term
research aim, therefore, is to develop a physiologically based pharmacokinetic
model (PBPK) to predict the dermal absorption and disposition of actives
included in complex dermatological products. This work explored whether in vitro release and skin permeation tests (IVRT and IVPT,
respectively), and in vitro and in vivo stratum corneum (SC) and viable tissue (VT) sampling data, can provide
a satisfactory description of drug “input rate” into
the skin and subsequently into the systemic circulation. In
vitro release and skin permeation results for scopolamine
were consistent with the previously reported performance of the commercial
patch investigated. New skin sampling data on the dermatopharmacokinetics
(DPK) of scopolamine also accurately reflected the rapid delivery
of a “priming” dose from the patch adhesive, superimposed
on a slower, rate-controlled input from the drug reservoir. The scopolamine
concentration versus time profiles in SC and VT skin compartments, in vitro and in vivo, taken together with
IVRT release and IVPT penetration kinetics, reflect the input rate
and drug delivery specifications of the Scopoderm transdermal patch
and reveal the importance of skin binding with respect to local drug
disposition. Further data analysis and skin PK modeling are indicated
to further refine and develop the approach outlined.