Studies in design and evaluation of iontophoretic drug delivery of cardiovascular drugs

Abstract

quotBackground: There are numbers of problem associated with conventional oral dosage forms, like poor absorption, local irritation, Hepatic metabolism, drug degradation, protein binding, high dose of a drug, and local toxicity. These demerits can be overcome by transdermal iontophoretic drug delivery. newline newlineAim: The purpose of the present investigation was to develop an iontophoretic device and formulation for a cardiovascular drug like Atenolol, Diltiazem HCl, and Captopril. newline newlineMaterials and Methods: Film formulations of the selected drug were prepared by using Hypromellose, Eudragit RLPO, Eudragit RSPO, Ethylcellulose, and combination of Ethylcellulose and polyvinyl pyrrolidone polymer. Polyethylene glycol 400 and Glycerin were used as a plasticizer. Similarly, gel formulations were prepared by using Carbopol, Hypromellose, Methylcellulose, and Sodium Carboxy Methyl Cellulose polymer. Prepared formulations were characterized by the different physicochemical parameter. Passive and iontophoretic in-vitro diffusion study was performed using a modified diffusion cell. The synergetic effect of chemical permeation enhancer on iontophoresis was evaluated using 1-Dodecyl azacycloheptan-2-one (Azone), Oleic acid, N-Methyl -2-pyrrolidone and Dimethyl sulfoxide as permeation enhancers. A fractional factorial design 24-1 was adapted for optimization of four formulation variables (current, drug concentration, permeation enhancer concentration, and radius of application area). A new iontophoretic device was developed and evaluated for a steady flow of current, proper voltage output, and skin irritation study. Stability study was performed on the finalized formulation. newline newlineResults and Discussion: Physico-chemical parameters of all prepared film and gel formulation were found satisfactory. Maximum enhancement ratio observed for Diltiazem HCl film prepared by using ethyl cellulose was 2.07, which indicates no significant enhancement in iontophoretic flux compared to passive iontophoresis for film formulation. For Atenolol, Diltiazem HCl