Abstract
Rosuvastatin is a hepato-selective statin of limited water solubility and poor oral bioavailability. The rationale behind this work was to develop pullulan based freeze-dried orodispersible tablets containing rosuvastatin flexible lipid-based nanoparticles (transfersomes) to enhance rosuvastatin bioavailability and hypolipidemic activity. Drug loaded transfersomes were prepared, characterized, and loaded into pullulan based freeze-dried orodispersible tablets. The prepared tablets were evaluated for their quality attributes and in vivo disintegration time. The pharmacokinetic behavior of the prepared tablets was studied on male Wistar rats and compared to commercial drug tablets. The hypolipidemic, hepatic enzyme and antioxidant activities were also assessed in poloxamer-induced hyperlipidemic rats. Hepatotoxicity was also investigated. The developed transfersomes showed oval irregular shape vesicles and illustrated an average vesicle size of about 230.34 ± 8.73 nm, a polydispersity index value of 0.508 ± 0.075, a zeta potential value of −10.29 ± 0.46 mV and an entrapment efficiency of 78.13 ± 0.54%. The prepared tablets were complying with the pharmacopeial standards for orodispersible tablets specification. The relative bioavailability of the orodispersible tablets was found to be 133.59%. The prepared orodispersible tablets were more effective than the commercial drug product in reducing the serum lipids, and improving the hepatic enzyme and serum antioxidant levels. No remarkable histopathological changes were observed. So, pullulan based freeze-dried orodispersible tablets loaded with rosuvastatin transfersomes are an effective and safe therapeutic dosage form in treatment of hyperlipidemia, but more preclinical and clinical investigations are required.
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