IONTOPHORESIS ASSISTED TRANSDERMAL DELIVERY OF PERINDOPRIL ERBUMINE GEL FORMULATION

Abstract

Hypertension affects nearly 78 million adults in the US every year. Perindopril erbumine (PE) is an ACE inhibitor used to treat hypertension, coronary artery disease, and heart failure. Traditional dosage forms such as tablets provide a challenge for patients to comply with the therapeutic regimen. Transdermal delivery can address major side effects of PE such as low bioavailability, poor conversion into perindoprilat, and low intestinal absorption. Physical enhancement techniques like microneedles and iontophoresis are used to increase the delivery of molecules into and across the skin. In-vitro permeation using cathodal and anodal iontophoresis was conducted on porcine ear skin. The current density was set at 0.5 mA/cm2 for 4 h which was followed by passive permeation up to 24 h. Further, 1% PE gel in hydroxypropylcellulose was formulated and characterized for pH and rheology. Cathodal iontophoresis was conducted on gel, and samples were analyzed by HPLC. The total delivery of PE via passive permeation was 98.56 ± 11 μg/cm2. Iontophoresis resulted in a significant increase in the total delivery of PE of 269.27 ± 19 11 μg/cm2 through anodal and 285.48 ± 4 μg/cm2 via cathodal iontophoresis. Significant decrease in lag time of PE was observed in cathodal iontophoresis. The total delivery from gel formulation via passive permeation was 34.77 ± 9 μg/cm2 while through cathodal iontophoresis it was found to be 101.95 ± 4 μg/cm2 which reached the target delivery of 60 μg/cm2, equivalent to delivery from a 4 mg tablet, using a 50 sq.cm2 patch and taking into consideration the bioavailability. This study demonstrated the feasibility of iontophoretic transdermal delivery of perindopril erbumine.