Carvedilol- loaded Transdermal Ethosomal gel: Characterization, ex vivo/in vivo Evaluation

Abstract

Carvedilol (CAR) is a cardiovascular drug commonly used for the management of hypertension, heart failure and angina pectoris. However, it has low oral bioavailability due to pre-systematic breakdown by liver enzymes which necessitates multiple doses per day. The present study investigates the development of sustained release transdermal carvedilol-loaded ethosomal formulation. CAR- ethosomal formulation was prepared by cold method with1% lipid, 50mg Carvedilol, 30% ethanol (v/v) and sonication time 3 min. The prepared formulation was characterized for vesicle size, polydispersity index (PDI) and entrapment efficiency (EE%). The formula showed small vesicle size (46.75±9.41nm) and high EE% (97%). Accordingly, it was subjected to stability study, TEM and zeta potential analysis. The formula showed good physical stability at refrigeration temperature after 90 days storage period as well as good zeta potential of +38.75mV. Our formula exhibited spherical unilamellar structure under TEM. Consequently, our formula was made as gel using HPMC polymer and was tested for pH, spreadability, drug content, skin permeation and pharmacokinetic study by HPLC-MS technique. Plasma drug levels were measured for rats after administration of both ethosomal gel and oral carvedilol tablet. The pharmacokinetic parameters were calculated and compared between the transdermal and oral dosage forms. Our formula showed lower t max and higher AUC0-24 than oral carvedilol tablet. Our findings affirm the potential of ethosomes as new vesicular carriers in sustained transdermal management of common cardiovascular conditions.