Thesis (M.Sc.) - Cairo University - Faculty of Pharmacy - Department of Pharmaceutics

Atorvastatin calcium (ATC) is an HMG-CoA reductase inhibitor, efficiently exerting its action by competitively inhibiting the HMG-CoA reductase enzyme, interfering with cholesterogenesis in the liver. It also decreases the level of LDL by increasing its reuptake and degradation. Additionally, it has been shown to decrease the progression of coronary atherosclerosis, by shrinking the lipid core of the plaque. The main drawback of oral ATC is its limited bioavailability of 12 - 14%, this is attributed to pre-systemic gastrointestinal clearance and extensive hepatic first-pass metabolism. In order to overcome this poor bioavailability, ATC is administered in high doses which results in patients being susceptible to more serious adverse effects including; arthralgia, severe muscle toxicity such as rhabdomyolysis, liver abnormalities and might lead to kidney failure. Hence the present study aims to develop ATC transdermal proniosomes to allow drug to penetrate the skin avoiding portal circulation, possessing its anti-hyperlipidemic effect ameliorating its orally induced hepatotoxicity.The ATC loaded proniosomal gels were prepared for transdermal delivery, characterized and evaluated regarding in vitro physicochemical properties, ex vivo skin permeation, and in vivo performance in terms of anti-hyperlipidemic efficacy and ATC safety profile regarding hepatocellular damage. From literature, only few reports investigated the transdermal delivery of ATC from proniosomesز To the best of our knowledge, there was no previous investigation made to fully explore transdermal proniosomal ATC pharmacodynamic efficacy along with its ability to ameliorate the drug side effects specially liver toxicity commonly associated with statins

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