In vitro skin penetration and skin content of progesterone from various topical formulations

Progesterone has been compounded by pharmacists over the last decade using a variety of different dosage forms including, suppositories, troches, solutions, capsules, nasal sprays, creams, ointments, and gels. In particular, the topical/transdermal route has become very popular among physicians, compounders, and patients. There are a few studies in the medical literature that address the transdermal permeation of progesterone from topically applied dosageforms. The results are typically controversial with some studies showing permeation and others showing little to no permeation. Coupled with the high saliva levels that are often seen in patients undergoing topical/transdermal treatment with progesterone and the accompanying lack of progesterone blood levels, the transdermal route of delivery for progesterone is controversial. In this study, we examined the transdermal penetration of progesterone from four different formulations and the skin retention of progesterone in porcine skin. Our results indicate that only minute quantities of progesterone transdermally penetrated through the porcine skin. However, there was significant partitioning of progesterone in the skin tissues. Consequently, these results suggest that the lymphatic circulation that exists in the skin may potentially account for the systemic delivery of topically applied progesterone that is often observed clinically.