1120 In vitro percutaneous absorption of extemporaneously compounded estradiol formulations

Extemporaneously compounded bioidentical hormones are commonly dispensed in the United States. However, questions have been raised regarding the safety, effectiveness and use of compounded hormone replacement therapy (cHRT). There is a need for clinical and scientific evidence on cHRT, in particular regarding topically applied hormones. An in vitro study was conducted to evaluate the human skin percutaneous absorption of topically applied estradiol, using the Franz Skin Finite Dose Model. An aqueous compounded cream (VersaBase Cream) and an anhydrous compounded gel (VersaBase Anhydrous HRT) were prepared for estradiol 0.06%, and also for estradiol 0.06% / estriol 0.1% (biest). The commercial medication ESTROGel (estradiol 0.06%) was used as positive control. Estradiol concentrations were analyzed using ELISA. The aqueous and anhydrous extemporaneously compounded formulations exhibited similar rate of absorption, characterized by a steady mean flux that increased slightly up to around 8 hours, and decreased slightly towards the end of the study (24 hours). The ESTROGel, on the other hand, exhibited a quick rise in skin percutaneous absorption to a peak at approximately 1 hour after dose application, followed by a quick decline in flux over time (up to 4 hours), and then decreased slightly as well towards the end of the study. Upon 24 hours of topical application, the mean cumulative absorption of estradiol for biest anhydrous compounded gel, estradiol anhydrous compounded gel, biest aqueous compounded cream, estradiol aqueous compounded cream and ESTROGel was 1080.9±862.8 ng/cm2, 1073.6±668.8 ng/cm2, 752.8±405.9 ng/cm2, 737.2±313.6 ng/cm2 and 516.8±158.1 ng/cm2, respectively. It is demonstrated that estradiol penetrates through the skin upon topical application of aqueous and anhydrous compounded formulations. These results are important evidence to support the effectiveness of cHRT since the in vitro model used has proven to accurately predict in vivo permeation kinetics.