Bioavailability of nerodilol-based transdermal therapeutic system of nicorandil in human volunteers.
The objective of the present investigation was to design and evaluate a nerodilol-based transdermal therapeutic system (TTS) for finding its ability in providing the desired steady-state plasma concentration of nicorandil in human volunteers. The influence of EVA2825 membrane, adhesive-coated EVA2825 membrane and adhesive-coated EVA2825-rat skin composite on the in vitro permeation of nicorandil from a nerodilol-based HPMC gel drug reservoir was studied against a control (excised rat skin alone). The flux of nicorandil from the nerodilol-based HMPC drug reservoir across excised rat skin (control) was 384.0+/-4.6 microg/cm2 h and this decreased to 222.7+/-7.1 microg/cm2 h when studied across EVA2825 membrane indicating that EVA2825 membrane was effective as rate controlling membrane. The flux of the drug decreased to 183.8+/-5.7 microg/cm2 h on application of a water-based acrylic adhesive (TACKWHITE A 4MED) coat to EVA2825 membrane. However, the flux of nicorandil across adhesive-coated EVA2825-membrane-rat-skin composite was 164.8+/-1.8 microg/cm2 h, which was 1.74-times of the required flux that prompted for preparation of TTS. The nerodilol-based drug reservoir system was sandwiched between a composite of adhesive-coated EVA2825 membrane-release liner and a backing membrane. The resultant sandwich was heat-sealed to produce circle-shaped TTS (20 cm2) that were subjected to bioavailability study in human volunteers against immediate release nicorandil tablet. The nerodilol-based TTS provided a steady-state plasma concentration of 25.5 ng/ml for 24 h in human volunteers. It was concluded that the nerodilol-based TTS of nicorandil provided the desired plasma concentration of the drug for the predetermined period of time with minimal fluctuations.
Department of Pharmaceutics, Faculty of Pharmacy, Kuwait University, PO Box 24923, Safat 13110, Kuwait. ysrkrishnaiah@hsc.edu.kw
Y S R
YS
Krishnaiah
S M
SM
Al-Saidan
D V
DV
Chandrasekhar
V
V
Satyanarayana
D000279:Administration, Cutaneous; D000328:Adult; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D001682:Biological Availability; D018592:Cross-Over Studies; D004337:Drug Carriers / Q000737:chemistry*; D005782:Gels; D006801:Humans; D065347:Hypromellose Derivatives; D066298:In Vitro Techniques; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives*; D020108:Nicorandil / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D011108:Polymers / Q000737:chemistry; D051381:Rats; D012717:Sesquiterpenes; D012869:Skin Absorption; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D014753:Vinyl Compounds / Q000737:chemistry
D000889:Anti-Arrhythmia Agents; D004337:Drug Carriers; D005782:Gels; D011108:Polymers; D012717:Sesquiterpenes; D014665:Vasodilator Agents; D014753:Vinyl Compounds; C057352:ethyl vinyl acetate; D020108:Nicorandil; D065347:Hypromellose Derivatives; D008747:Methylcellulose; C011566:vinyl acetate; C037055:nerolidol