Category: Formulation and Quality
Purpose: Transdermal hormonal therapy (THT) delivers the exogenous hormones directly to the systemic circulation. Transdermal estrogen, progesterone or testosterone products are formulated as drug-in-adhesive type of transdermal delivery systems (TDS), emulsions or gels. These products are applied on the abdomen, thigh, shoulders and upper arms. It has been reported that residual hormones on the skin have the potential of transfer to healthy individuals via skin contact with the application site for up to 8 hours post application. This hormone transfer to healthy individuals may cause clinically significant hormonal imbalance and adverse effects. Currently, there is no in vitro methodology for assessing the risk of skin-to-skin drug transfer. Therefore, the purpose of the current study is to develop novel in vitro model to predict risk of skin-to-skin drug transfer during transdermal hormonal replacement therapy.
Methods: The study aimed at developing a novel in vitro permeation methodology using vertical diffusion cells to evaluate this risk. A model testosterone transdermal gel was employed. The risk of skin-to-skin transfer of drug after various durations of application followed by washing was evaluated. The dosed skin samples were then transferred over the surface of fresh skin samples for permeation and mass balance testing (Figure 1).
Results: The results demonstrated that the amount of the hormone recovered from dosed skin increased by increasing the residence time of the gel on the skin surface. The extent of drug transfer and permeation from the dosed to fresh skin samples was directly proportional to the amount of drug retained by the dosed skin. Also, It has been observed that the amount of the drug retained by the dosed skin is equilibrating with the new skin based on the drug reservoir size in each skin sample.
Conclusion: Therefore, this study provided a novel in vitro method that can be used in predicting the risk of skin-to-skin drug transfer during THT.