Solusomes (novel soluplus® enriched nano-vesicular carriers) for improving the oral bioavailability of Candesartan cilexetil

Abstract

Candesartan cilexetil (CAN) is administered for treating hypertension and heart failure. CAN suffers poor oral bioavailability, owing to limited aqueous solubility, and first-pass metabolism. Solusomes (novel Soluplus® enriched nano-vesicular carriers) combine the merits of Soluplus®, and the traditional liposomes. They were explored to increase CAN solubility, allow a high drug release rate, and improve the oral drug bioavailability. Solusomes were developed via thin film hydration technique utilizing lipid (phosphatidylcholine; PC) and polymeric solubilizer (Soluplus®; Solu). S6 system comprising PC (0.1% w/v), CAN and Soluplus® (at 1:5 ratio; w/w), following a 5 min sonication period, was the optimum one with respect to drug entrapment efficiency (83.5 ± 2.6%), drug loading (11.9 ± 0.3%), particle size and shape (377.2 ± 12.1 nm, spherical), zeta-potential (−19.6 ± 2.1 mV), saturated drug solubility (32.09 ± 0.71 µg/mL), drug released % after 1 h (68 ± 0.9%), and stability. Significantly higher Cmax (969.12 ± 46.3 ng/mL), shorter median Tmax (1h), and improved relative bioavailability (≈ 6.8 folds) in rabbits could evidence the potential of S6 system in enhancing oral CAN bioavailability. S6 solusomes act as dual platform to improve the oral drug bioavailability and maintain effective drug concentration for a prolonged period.