Design, formulation and optimization of valsartan transdermal gel containing iso-eucalyptol as novel permeation enhancer: preclinical assessment of pharmacokinetics in Wistar albino rats.
OBJECTIVE
The aim of this study was to develop and optimize a transdermal gel formulation of valsartan using Box-Behnken design and to evaluate it for pharmacokinetic study.


METHODS
The independent variables were Carbopol 940 (X1), PEG 400 (X2) and ethanol (X3) while valsartan flux (Y1), Tlag (Y2) and gel viscosity (Y3) were the dependent variables. Iso-eucalyptol was added in all gel formulations as permeation enhancer except for control gel.


RESULTS
It was observed that the permeation rate of valsartan significantly increased in direct proportion to the ethanol concentration, but significantly decreased in direct proportion to polymer concentration. Lag time and viscosity decreased in reverse proportion to ethanol concentration. The optimized valsartan gel formulation (VGF-OPT) yielded flux of 143.27 ± 7.11 µg/cm(2)/h and 27.55 ± 2.51 µg/cm(2)/h across rat and human cadaver skin, respectively. In vivo pharmacokinetic study of VGF-OPT-transdermal therapeutic system containing iso-eucalyptol showed a significant increase in the bioavailability (2.52 times) compared with oral formulation of valsartan by virtue of better permeation through Wistar rat skin.


CONCLUSIONS
It was concluded that the developed transdermal gel accentuates the flux of valsartan and could be used as an antihypertensive dosage form for effective transdermal delivery of valsartan.
King Saud University, College of Pharmacy, Department of Pharmaceutics , Riyadh 11451 , Saudi Arabia abdulahad20@yahoo.com.
Abdul
A
Ahad
Mohd
M
Aqil
Kanchan
K
Kohli
Yasmin
Y
Sultana
Mohd
M
Mujeeb
D000279:Administration, Cutaneous; D047228:Angiotensin II Type 1 Receptor Blockers / Q000737:chemistry* / Q000493:pharmacokinetics*; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D003511:Cyclohexanols / Q000737:chemistry*; D004339:Drug Compounding; D016503:Drug Delivery Systems; D000077591:Eucalyptol; D005782:Gels; D006801:Humans; D039821:Monoterpenes / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D012997:Solvents / Q000737:chemistry*; D013777:Tetrazoles / Q000737:chemistry* / Q000493:pharmacokinetics*; D014633:Valine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D000068756:Valsartan; D014783:Viscosity
D047228:Angiotensin II Type 1 Receptor Blockers; D003511:Cyclohexanols; D005782:Gels; D039821:Monoterpenes; D012997:Solvents; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine; D000077591:Eucalyptol
Box-Behnken design; iso-eucalyptol; pharmacokinetic; transdermal and valsartan