Investigation of skin-to-skin transfer risks of topically applied transdermal hormonal drugs
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Contributing OfficeCenter for Drug Evaluation and Research
Abstract
Background
Hormonal drugs are widely used by patients for the treatment of hormonal deficiencies and imbalances. If left untreated, such conditions may result in body weight fluctuation, fatigue, muscle weakness, sexual dysfunction, delayed puberty, mood swings, pain, depression, and many other symptoms. Testosterone and estradiol transdermal drug products are the most prescribed medications for transdermal hormonal replacement therapy. These medications are available in several dosage forms including patches, gels, emulsions, creams, and sprays. A major risk associated with transdermal hormonal replacement therapy is the potential for skin-to-skin drug transfer from a dosed individual to a healthy individual (e.g. partner, children, pets). Often, the topically applied residual drug on the skin may be transferred to an undosed individual during intended or unintended skin to skin contact. In fact, it has been reported that this skin to skin transfer of testosterone or estradiol transdermal drug products has resulted in adverse cardiac events in men; hyperandrogenism, hirsutism, acne, and male-pattern baldness in women; and early puberty or premature epiphyseal closure of bones in children (Busse, K. L., & Maibach, H. I., 2011). As such, it is important to understand the correlation between the type of dosage form and the physiochemical properties of the formulation excipients that might be responsible for enhancing the potential risk of drug transfer from the dosed to the healthy individual.
Method
As a part of an ongoing OTR research project, an extensive literature review has been performed to investigate available methods to evaluate the risks of drug transfer from a dosed individual to a healthy individual.
Results/Conclusion
The result obtained from literature review shows that many clinical in vivo studies have been performed to evaluate the risk of transdermal hormonal drug transfer in various skin-to-skin contact scenarios. It was found that testosterone gels and estradiol emulsions were the two dosage forms that posed the greatest risk of skin-to-skin transfer from the dosed individual to healthy individual. For example, the in vivo skin to skin transfer study of 1.62% testosterone gel showed that testosterone levels in female partners increased to 86-185% of the baseline following direct contact with their male partners (Stahlman, Jodi, et al., 2012). Similarly in another study, skin-to-skin contact following application of topical estradiol emulsion was found to increase the systemic average estradiol concentration by 25% in male partners (Taylor, M. B., & Gutierrez, M. J., 2008). However, currently no in vitro methodologies are available to assess this risk. Moreover, the effects of physiochemical properties of the formulation excipients on the potential skin to skin drug transfer has not been reported. As such, the current OTR research aims to develop an in vitro permeation method to identify critical formulation variables that may promote skin-to-skin drug permeation of such drug products. This in vitro method will employ human cadaver skin and Franz diffusion cells. This study will also employ different dosing scenarios and skin-to-skin contact possibilities.