title: In vivo evaluation of limonene-based transdermal therapeutic system of nicorandil in healthy human volunteers.
abstract: Hydroxypropyl methylcellulose (HPMC) gel drug reservoir system prepared with 70:30 v/v ethanol-water solvent system containing 6% w/w of limonene was effective in promoting the in vitro transdermal delivery of nicorandil. The objective of the present study was to fabricate and evaluate a limonene-based transdermal therapeutic system (TTS) for its ability to provide the desired steady-state plasma concentration of nicorandil in human volunteers. The in vitro permeation of nicorandil from a limonene-based HPMC gel drug reservoir was studied across excised rat skin (control), EVA2825 membrane, adhesive-coated EVA2825 membrane and adhesive-coated EVA2825 membrane-excised rat skin composite to account for their effect on the desired flux of nicorandil. The flux of nicorandil from the limonene-based HMPC drug reservoir across EVA2825 membrane decreased to 215.8 +/- 9.7 microg/cm(2).h when compared to that obtained from control, indicating that EVA2825 was effective as a rate-controlling membrane. The further decrease in nicorandil flux across adhesive-coated EVA2825 membrane and adhesive-coated EVA2825 membrane-excised rat skin composite showed that the adhesive coat and skin also controlled the in vitro transdermal delivery. The limonene-based drug reservoir was sandwiched between adhesive-coated EVA2825-release liner composite and a backing membrane. The resultant sandwich was heat-sealed as circle-shaped patch (20 cm(2)), trimmed and subjected to in vivo evaluation in human volunteers against immediate-release tablets of nicorandil (reference formulation). The fabricated limonene-based TTS of nicorandil provided a steady-state plasma concentration of 21.3 ng/ml up to 24 h in healthy human volunteers. It was concluded that the limonene-based TTS of nicorandil provided the desired plasma concentration of the drug for the predetermined period of time with minimal fluctuations and improved bioavailability.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Health Science Center, Kuwait University, Kuwait. ysrkrishnaiah@hsc.edu.kw
authors.forename: Y S R
authors.initials: YS
authors.lastname: Krishnaiah
authors.forename: D V
authors.initials: DV
authors.lastname: Chandrasekhar
authors.forename: B
authors.initials: B
authors.lastname: Rama
authors.forename: B
authors.initials: B
authors.lastname: Jayaram
authors.forename: V
authors.initials: V
authors.lastname: Satyanarayana
authors.forename: S M
authors.initials: SM
authors.lastname: Al-Saidan
mesh_terms: D000279:Administration, Cutaneous; D000284:Administration, Oral; D000328:Adult; D000818:Animals; D019540:Area Under Curve; D018592:Cross-Over Studies; D053138:Cyclohexenes; D016503:Drug Delivery Systems; D005542:Forearm; D005782:Gels; D006801:Humans; D065347:Hypromellose Derivatives; D000077222:Limonene; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives; D020108:Nicorandil / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D010539:Permeability; D051381:Rats; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D012997:Solvents; D013729:Terpenes; D014014:Tissue Adhesives; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics
chemical_list: D053138:Cyclohexenes; D005782:Gels; D012997:Solvents; D013729:Terpenes; D014014:Tissue Adhesives; D014665:Vasodilator Agents; D020108:Nicorandil; D065347:Hypromellose Derivatives; D008747:Methylcellulose; D000077222:Limonene