The application of anethole, menthone, and eugenol in transdermal penetration of valsartan: Enhancement and mechanistic investigation.
BACKGROUND
The main barrier for transdermal delivery is the obstacle property of the stratum corneum. Many types of chemical penetration enhancers have been used to breach the skin barrier; among the penetration enhancers, terpenes are found as the most highly advanced, safe, and proven category.


OBJECTIVE
In the present investigation, the terpenes anethole, menthone, and eugenol were used to enhance the permeation of valsartan through rat skin in vitro and their enhancement mechanism was investigated.


METHODS
Skin permeation studies of valsartan across rat skin in the absence and the presence of terpenes at 1% w/v, 3% w/v, and 5% w/v in vehicle were carried out using the transdermal diffusion cell sampling system across rat skin and samples were withdrawn from the receptor compartment at 1, 2, 3, 4, 6, 8, 10, 12, and 24 h and analysed for drug content by the HPLC method. The mechanism of skin permeation enhancement of valsartan by terpenes treatment was evaluated by Fourier transform infrared spectroscopy (FTIR) analysis and differential scanning calorimetry (DSC).


RESULTS
All the investigated terpenes provided a significant (p < 0.01) enhancement in the valsartan flux at a concentration of 1%, and less so at 3% and 5%. The effectiveness of terpenes at 1% concentration was in the following order: anethole > menthone > eugenol with 4.4-, 4.0-, and 3.0-fold enhancement ratio over control, respectively. DSC study showed that the treatment of stratum corneum with anethole shifted endotherm down to lower melting point while FTIR studies revealed that anethole produced maximum decrease in peak height and area than other two terpenes.


CONCLUSIONS
The investigated terpenes can be successfully used as potential enhancers for the enhancement of skin permeation of lipophilic drug.
a Department of Pharmaceutics , College of Pharmacy, King Saud University , Riyadh , Saudi Arabia ;
Abdul
A
Ahad
b Department of Pharmaceutics , Faculty of Pharmacy, Jamia Hamdard (Hamdard University) , New Delhi , India.
Mohd
M
Aqil
b Department of Pharmaceutics , Faculty of Pharmacy, Jamia Hamdard (Hamdard University) , New Delhi , India.
Asgar
A
Ali
D000279:Administration, Cutaneous; D000081248:Allylbenzene Derivatives; D000818:Animals; D000840:Anisoles / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D002152:Calorimetry, Differential Scanning; D005054:Eugenol / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D008610:Menthol / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D010539:Permeability; D017208:Rats, Wistar; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*; D017550:Spectroscopy, Fourier Transform Infrared; D000068756:Valsartan / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000081248:Allylbenzene Derivatives; D000840:Anisoles; D008610:Menthol; D005054:Eugenol; D000068756:Valsartan; C019466:menthone; C006578:anethole
Hypertension; permeation enhancer; terpenes