Experimental design, formulation, and in-vivo evaluation of novel anticoagulant Rivaroxaban loaded cubosomes in rats model

Abstract

The aim of this study was to develop novel cubosomes as an oral delivery system to improve the permeation and anti-clotting activity of Rivaroxaban (RX). The experimental design (23 full factorial design) was employed to study individual and combined impacts of the assigned formulation variables. The variables RX amount (X1), Poloxamer (PX): GMO (GMO) ratio (X2) and PX/GMO: water ratio (X3) were taken as independent factors, and their effect was examined on entrapment efficiency (Y1), particle size (Y2), and zeta potential. (Y3). The cubosomal vesicle RX-C 3 composed of RX (20 mg), PX: GMO (1:0.5 % w/w), and PX/GMO: water (1:5% w/w) is the optimised formula achieving the required prerequisites. RX-C 3 had shown a vesicle size of 91.2 ± 1.3 nm, entrapment efficiency of 96.27 ± 0.12 %, and zeta potential of −24.1 ± 0.2 mV. The in-vivo studies showed revealed good inhibition of blood clotting, where RX-C 3 significantly increased clotting time by 35% and prothrombin time by 29% compared to Rivarospire®. In conclusion, the present study suggested that oral cubosomes formulations provide prolonged delivery of Rivaroxaban.