Bioavailability of nerodilol-based transdermal therapeutic system of nicorandil in human volunteers

• Published in: Journal of controlled release 2005-08, Vol.106 (1), p.111-122
• Main Authors: Krishnaiah, Y.S.R., Al-Saidan, S.M., Chandrasekhar, D.V., Satyanarayana, V.
• Format: Article
• Language: English
• Subjects: Administration, Cutaneous; Adult; Animals; Anti-Arrhythmia Agents - administration & dosage; Anti-Arrhythmia Agents - blood; Anti-Arrhythmia Agents - pharmacokinetics; Bioavailability; Biological and medical sciences; Biological Availability; Cross-Over Studies; Drug Carriers - chemistry; Gels; General pharmacology; Human volunteers; Humans; Hypromellose Derivatives; In Vitro Techniques; Male; Medical sciences; Methylcellulose - analogs & derivatives; Nerodilol; Nicorandil; Nicorandil - administration & dosage; Nicorandil - blood; Nicorandil - pharmacokinetics; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polymers - chemistry; Preparation; Rats; Sesquiterpenes; Skin Absorption; TTS; Vasodilator Agents - administration & dosage; Vasodilator Agents - blood; Vasodilator Agents - pharmacokinetics; Vinyl Compounds - chemistry
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2005.04.021

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 μg/cm 2 h and this decreased to 222.7 ± 7.1 μg/cm 2 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 μg/cm 2 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 μg/cm 2 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 cm 2) 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.