Role of novel terpenes in transcutaneous permeation of valsartan: effectiveness and mechanism of action.

BACKGROUND

The greatest obstacle for transdermal delivery is the barrier property of the stratum corneum. Many approaches have been employed to breach the skin barrier; the most widely used one is that of chemical penetration enhancers. Of the penetration enhancers, terpenes are arguably the most highly advanced and proven category.

OBJECTIVE

The aim of this investigation was to study effectiveness and mechanism of seven novel terpenes, namely iso-eucalyptol, β-citronellene, valencene, rose oxide, safranal, lavandulol acetate, and prenol, as potential penetration enhancers for improved skin permeation of valsartan through rat skin and human cadaver skin (HCS) with reference to established terpene eucalyptol.

METHODS

Skin permeation studies were carried out using Automated Transdermal Diffusion Cell Sampling System (SFDC 6, LOGAN Instruments Corp., NJ) on rat skin and HCS. The mechanism of skin permeation enhancement of valsartan by terpenes treatment was evaluated by Fourier transform infrared spectroscopy (FT-IR) analysis, differential scanning calorimetry (DSC) thermogram, and histopathological examination.

CONCLUSIONS

Among all study enhancers, iso-eucalyptol produced the maximum enhancement via rat skin [enhancement ratio (ER) = 7.4] and HCS (ER = 3.60) over control. FT-IR spectra and DSC thermogram of skin treated with aforesaid terpenes indicated that permeation occurred due to the disruption of lipid bilayers. No apparent skin irritation (erythema, edema) was observed on treatment with terpenes except β-citronellene, safranal, lavandulol acetate, and prenol, which caused mild irritation.

CONCLUSIONS

It is concluded that the iso-eucalyptol can be successfully used as safe and potential penetration enhancer for enhancement of skin permeation of lipophilic drug such as valsartan.