Abstract
For topical drug products that target sites of action in the viable epidermal and/or upper dermal compartment of the skin,
the local concentration profiles have proven difficult to quantify because drug clearance from the viable cutaneous tissue is
not well characterised. Without such knowledge, of course, it is difficult—if not impossible—to predict a priori whether and
over what time frame a topical formulation will permit an effective concentration of drug within the skin ‘compartment’ to
be achieved. Here, we test the hypothesis that valuable information about drug disposition, and specifically its clearance, in
this experimentally difficult-to-access compartment (at least, in vivo) can be derived from available systemic pharmacokinetic
data for drugs administered via transdermal delivery systems. A multiple regression analysis was undertaken to determine the
best-fit empirical correlation relating clearance from the skin to known or easily calculable drug properties. It was possible,
in this way, to demonstrate a clear relationship between drug clearance from the skin and key physical chemical properties
of the drug (molecular weight, log P and topological polar surface area). It was further demonstrated that values predicted
by the model correlated well with those derived from in vitro skin experiments.
the local concentration profiles have proven difficult to quantify because drug clearance from the viable cutaneous tissue is
not well characterised. Without such knowledge, of course, it is difficult—if not impossible—to predict a priori whether and
over what time frame a topical formulation will permit an effective concentration of drug within the skin ‘compartment’ to
be achieved. Here, we test the hypothesis that valuable information about drug disposition, and specifically its clearance, in
this experimentally difficult-to-access compartment (at least, in vivo) can be derived from available systemic pharmacokinetic
data for drugs administered via transdermal delivery systems. A multiple regression analysis was undertaken to determine the
best-fit empirical correlation relating clearance from the skin to known or easily calculable drug properties. It was possible,
in this way, to demonstrate a clear relationship between drug clearance from the skin and key physical chemical properties
of the drug (molecular weight, log P and topological polar surface area). It was further demonstrated that values predicted
by the model correlated well with those derived from in vitro skin experiments.
Original language | English |
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Pages (from-to) | 729–740 |
Number of pages | 12 |
Journal | Drug Delivery and Translational Research |
Volume | 11 |
Early online date | 8 Nov 2020 |
DOIs | |
Publication status | Published - 30 Apr 2021 |
Funding
This research was funded by the CAPES foundation (via the Brazilian ‘Science without Borders’ programme, grant number 13614-13-4), by the Austrian Science Fund (FWF, Erwin-Schrödinger fellowship number J3754-B30) and by The Leo Foundation (grant number LF16117).