methylcellulose and nerolidol

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.

Topics: Administration, Cutaneous; Adult; Animals; Anti-Arrhythmia Agents; Biological Availability; Cross-Over Studies; Drug Carriers; Gels; Humans; Hypromellose Derivatives; In Vitro Techniques; Male; Methylcellulose; Nicorandil; Polymers; Rats; Sesquiterpenes; Skin Absorption; Vasodilator Agents; Vinyl Compounds