Effect of nerodilol and carvone on in vitro permeation of nicorandil across rat epidermal membrane.
The objective of the study was to investigate the effect of nerodilol and carvone on the in vitro transdermal delivery of nicorandil so as to fabricate a membrane-moderated transdermal therapeutic system. The in vitro permeation studies were carried across the rat epidermal membrane from the hydroxypropyl methylcellulose (HPMC) gels (prepared with 70:30 v/v ethanol-water) containing selected concentrations of a terpene such as nerodilol (0%w/w, 4%w/w, 8%w/w, 10%w/w, or 12%w/w) or carvone (0%w/w, 4%w/w, 8%w/w, 12%w/w, or 16%w/w). The amount of nicorandil permeated (Q(24)) from HPMC gel drug reservoir without a terpene was 3424.6+/-51.4 microg/cm(2), and the corresponding flux of the drug was 145.5+/-2.2 microg/cm(2). h. The flux of nicorandil increased with an increase in terpene concentration in HPMC gel. It was increased ranging from 254.9+/-3.1 to 375.7+/-3.2 microg/cm(2).h or 207.6+/-4.7 to 356.7+/-15.3 microg/cm(2). h from HPMC gels containing nerodilol (4%w/w to 12%w/w) or carvone (4%w/w to 16%w/w), respectively. Nerodilol increased the flux of nicorandil by about 2.62-folds whereas carvone increased the flux of the drug by about 2.49-folds across the rat epidermal membrane. The results of the Fourier Transform Infrared (FT-IR) study indicated that the enhanced in vitro transdermal delivery of nicorandil might be due to the partial extraction of stratum corneum lipids by nerodilol or carvone. It was concluded that the terpenes, nerodilol and carvone, produced a marked penetration enhancing effect on the transdermal delivery of nicorandil that could be used in the fabrication of membrane-moderated transdermal therapeutic systems.
Krishnaiah
Yellela S R
YS
Department of Pharmaceutics, Faculty of Pharmacy, Kuwait University, Kuwait. ysrkrishnaiah@hsc.edu.kw
Al-Saidan
Saleh M
SM
Chandrasekhar
Dantam V
DV
Rama
Bukka
B
D000279:Administration, Cutaneous; D000818:Animals; D000081005:Cyclohexane Monoterpenes; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism*; D005782:Gels; D065347:Hypromellose Derivatives; D066298:In Vitro Techniques; D008747:Methylcellulose / Q000031:analogs & derivatives; D008954:Models, Biological; D039821:Monoterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D020108:Nicorandil / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010539:Permeability; D051381:Rats; D012869:Skin Absorption / Q000187:drug effects*; D017550:Spectroscopy, Fourier Transform Infrared; D013729:Terpenes / Q000008:administration & dosage / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000081005:Cyclohexane Monoterpenes; D005782:Gels; D039821:Monoterpenes; D013729:Terpenes; D014665:Vasodilator Agents; C508312:nerodilol; D020108:Nicorandil; D065347:Hypromellose Derivatives; C006923:carvone; D008747:Methylcellulose