Evaluation of the in vitro Human Skin Percutaneous Absorption of Progesterone in Versabase® Using the Franz Skin Finite Dose Model

Abstract

Women may benefit from hormone replacement therapy to alleviate undesirable menopausal symptoms such as hot flashes, disruption of sleep and fatigue. Transdermal hormone replacement therapy consists in the delivery of hormones through the skin and into the blood stream, avoiding gastrointestinal drug absorption difficulties and the first pass effect. Transdermal compounded medications may be customized to meet the individual needs of women by changing the hormones used, the respective concentrations and the medicine's formulation. Two compounded medications were prepared for progesterone 50 mg/g, as follows: Progesterone in VersaBase ® Cream and progesterone in VersaBase ® Cream Gel. The purpose of this study is to determine the in vitro human skin percutaneous absorption of progesterone for both test formulations. The Franz Skin Finite Dose Model was the methodology used to evaluate the total absorption, the rate of absorption and the skin content of progesterone applied to the outer surface of ex vivo skin. This model has proven to be a valuable tool for the study of percutaneous absorption of topically applied drugs and to accurately predict in vivo permeation kinetics. The skin samples were obtained within 24 h to 48 h of death from three adult Caucasian donors and a total of 17 Franz diffusion chambers were prepared for testing. Results are presented as the mean ± standard error per parameter, for each test formulation. The rate of percutaneous absorption, presented as mean flux, was similar for the two test formulations and characterized by 2 peaks at approximately 6 hours and 28 hours after dose application, followed by a decline in flux over time. The total absorption and the skin content of progesterone were also similar: 21.6% and 21.8% of the applied doses for the test formulations 1 and 2, respectively. Although in vitro, these results suggest that progesterone in VersaBase ® is likely to be delivered through the skin and into the general circulation for systemic effects. Practitioners may then consider transdermal progesterone as a viable route of drug administration for menopausal women.

Evaluation of a compounding phospholipid base for the percutaneous absorption of high molecular weight drugs using the Franz finite dose model

“…The chemical composition of the compounding bases for topical formulations plays a key role in the penetration of the APIs across the skin barrier. [11][12][13][14] Lipoderm and Lipoderm HMW, also referred to as phospholipid bases, are proprietary compounding bases likely to increase the permeation of drugs. Lipoderm HMW, in particular, was designed to deliver HMW drugs into and through the skin.…”

“…Both phospholipid bases consist of a proprietary liposomal component shown to successfully facilitate the penetration of drugs into and through ex vivo human skin under in vitro conditions. Phospholipid bases have been shown to improve percutaneous absorption of promethazine hydrochloride, 11 lorazepam, 16 tramadol, 17 and other drugs 18 . However, the ability of the phospholipid bases to facilitate the skin absorption of HMW drugs remains unexplored.…”

“…Another method with growing research interest is the incorporation of APIs into topical permeation enhancing drug delivery vehicles/bases, which are increasingly used in pharmaceutical compounding to deliver medications across the skin. The chemical composition of the compounding bases for topical formulations plays a key role in the penetration of the APIs across the skin barrier 11–14 …”

“…to improve percutaneous absorption of promethazine hydrochloride, 11 lorazepam, 16 tramadol, 17 and other drugs. 18 However, the ability of the phospholipid bases to facilitate the skin absorption of HMW drugs remains unexplored.…”