Evaluation of Passive and Iontophoretic Transport of Lisinopril from Hydrogel Matrix Across Model Membrane In Vitro

Abstract

Clinical studies of lisinopril delivery through iontophoresis are highly desired for better controls over transdermal drug flux. Therefore, investigations were carried out to ascertain the relative importance of the various factor for iontophoretic transport using an ionizable drug lisinopril, which has four pKa values 2.4, 4.0 (for amino group) and 6.7, 7.0 (for carboxylic group). Ionization of lisinopril varies with pH, hence rate and extent of transport across the skin can be enhanced, controlled and manipulated by the application of factors like anodal and cathodal current at varied pH of donor solution and current densities. To determine these parameters, experiments were performed and data were collected at 3.0, 4.0 and 7.4 pH using 4 mg/ml drug concentration and 0.1 mA/cm2 current density for 10 hours. After establishing the pH for optimum transport of drug, effect of current density (0.1, 0.2, 0.3 and 0.4 mA/cm2) on the transport of drug (keeping drug concentration constant) were investigated. Passive diffusion of lisinopril was maximal at pH 3.0, when unionized form of drug was 45%. Anodal iontophoresis was most effective (significant result, p less than 0.05) in transport of drug across skin as compared to cathodal iontophoresis at pH 3.0. While at pH 4.0, cathodal iontophoretic transport of lisinopril across rat skin was highly effective (Student‘t’ test, p less than 0.05) compared to anodal iontophoresis. The effect of current density on steady state flux of lisinopril during cathodal iontophoresis at 7.4 pH was 1.33 ± 1.12 and 24.8 ± 3.1 μg/cm2/h at 0.0 under passive diffusion and 4 mA/cm2, respectively. Thus, flux was enhanced nearly 18.6 times during anodal iontophoresis as compared to passive diffusion. For cathodal flux at pH 3.0 on similar iontophoretic treatment showed enhancement nearly 4 times.