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.
Krishnaiah
Y S R
YS
Department of Pharmaceutics, Faculty of Pharmacy, Kuwait University, PO Box 24923, Safat 13110, Kuwait. ysrkrishnaiah@hsc.edu.kw
Al-Saidan
S M
SM
Chandrasekhar
D V
DV
Satyanarayana
V
V
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