Effect of p-menthane derivatives on skin permeation of paroxetine

Paroxetine, which is one of the most frequently prescribed antidepressants, is marketed as an oral preparation; however, a transdermal system is required to improve the patients' adherence. In this study, we attempted to enhance the penetration of paroxetine using p-menthane derivatives. The results from in vitro skin permeation studies indicate that the permeability of paroxetine can be increased greatly by using a paroxetine hydrogel containing p-menthane derivatives. The enhancement effect was affected by the thermodynamic activity of the derivatives in the hydrogel. In addition, we performed quantitative structure-activity relationship (QSAR) studies to relate the enhancement effect to the physicochemical properties of the p-menthane derivatives. The results of the QSAR studies indicated that the partition coefficient, absolute electron negativity, polarizability, solvent-accessible surface area and dipole moment of the p-menthane derivatives are important factors related to their enhancement effect. These results support the feasibility of delivering paroxetine transdermally using p-menthane derivatives.