Topical Formulations Containing Finasteride. Part I: In Vitro Permeation/Penetration Study and In Vivo Pharmacokinetics in Hairless Rat

In hair follicle (Hf) cells, the type-2 5-α-reductase enzyme, implicated in androgenetic alopecia, is selectively inhibited by finasteride (FNS). Because an effective topical formulation to deliver FNS to Hf is currently unavailable, this investigation aimed at evaluating in vitro FNS skin permeation and retention through and into hairless rat and human abdominal skin. Four hydroxypropyl chitosan (HPCH)-based formulations (P-08–012, P-08–016, P-08–063, and P-08–064) and one anhydrous formulation without HPCH (P-10–008) were tested. The pharmacokinetics in plasma and skin after application of P-08–016 or P-10–008 on dorsal rat skin with single and repeated doses was investigated. P-08–016 performed the best in driving FNS to the reticular dermis without producing a high transdermal flux. Neither the in vivo single nor the repeated dose experiments produced plasma levels of FNS and no differences were found between formulations concerning skin retention. No increase in the amount of drug retained in the skin was obtained with the repeated dose experiment. In conclusion, the HPCH-based formulation P-08–016 might represent an alternative to systemic therapy for its ability to promote a cutaneous depot of FNS in the region of hair bulbs, minimizing systemic absorption even after repeated treatments. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:2307–2314, 2014