Rosuvastatin lyophilized tablets loaded with flexible chitosomes for improved drug bioavailability, anti-hyperlipidemic and anti-oxidant activity

Abstract

Rosuvastatin is a hypolipidemic drug of limited oral bioavailability. The aim was to develop rosuvastatin flexible chitosomes and loading into a pullulan-based tablet to improve the bioavailability and maximize the antihyperlipidemic and antioxidant activities. Chitosomes nanoparticles were developed and characterized. Pullulan-based lyophilized fast dissolving tablets were developed and evaluated. The tablets' outer and inner structures were morphologically investigated. In vivo disintegration of the prepared tablets was studied in healthy human volunteers. The pharmacokinetics, antihyperlipidemic, antioxidant, and biochemical markers activities were conducted after administration of the tablets into male Wister rats. Liver histopathology was also investigated. The prepared chitosomes illustrated an average particle size of 342.22 ± 2.90 nm, a zeta potential value of +28.87 ± 1.39 mV and a drug entrapment efficiency of 94.59 ± 1.62%. The developed tablets showed an acceptable quality control characteristics and in vivo disintegration time of 1.48 ± 0.439 min. Scanning electron microscopy revealed distinct porous surface and sponge-like inner structure. The chitosomes based tablets demonstrated higher relative bioavailability by more than 30% and 36% when compared with the corresponding pure rosuvastatin and the marketed drug tablets, respectively. Moreover, the chitosomes based tablets showed a significant improvement in the hepatic serum biomarkers and a dramatic decrease in the serum antioxidants in response to Poloxamer 407 intoxication. The prepared tablets did not exhibit marked histopathological changes in the hepatic tissues. Accordingly, the pullan-based lyophilized fast-dissolving tablets loaded with chitosomes nanoparticles could be considered as a promising drug formulation for enhancing rosuvastatin bioavailability and pharmacodynamics activity.

Keywords: Antioxidant; Chitosomes; Hypolipidemic activity; Lyophilized tablets; Pharmacokinetics; Pullulan; Rosuvastatin.