Controlled Release of a Vasodilator Drug through Membrane-controlled Transdermal Systems: Development, Characterization, and Ex-vivo Evaluation

Background: An attempt was made to develop and evaluate the membrane- controlled transdermal systems for the controlled release of nicorandil. The carbopol gel was selected as a drug reservoir, crosslinked blend membranes of XG and SA were selected as rate-controlled membranes (RCM), and a film of poly(vinyl alcohol) (PVA) was selected as the backing membrane. Aim: The aim of the current work was to formulate the membrane-controlled transdermal drug delivery systems for the effective delivery of a vasodilator, nicorandil, for the management of hypertension and angina pectoris, and in-vitro and ex-vivo evaluation of these developed formulations. Methods: Reservoir gel was evaluated for drug content, pH, viscosity, and RCMs by weight uniformity, thickness uniformity, differential scanning calorimetric (DSC) analysis, x-ray diffraction (XRD) analysis, scanning electron microscopy (SEM), water vapor transmission, skin irritation, and histopathology. Results: Depending on crosslink density, variation in the water vapor permeation of RCMs was noticed. The RCMs showed no signs of skin irritation. In-vitro drug permeation through rat skin was extended for a period of 24 hours. With an increase in acetaldehyde concentration in the RCM, there was a decrease in drug permeation. Among the two terpenes used as penetration enhancers, the cineole at a concentration of 20% exhibited a maximum permeation rate. The release mechanism from all systems followed non-Fickian transport. Histopathology results indicated minor changes in skin structure after skin permeation studies, which were reversible. Conclusion: The developed transdermal systems were found to have versatile dosage forms for the controlled release of nicorandil, a vasodilator.