Oral Nanoparticulate Atorvastatin Calcium is More Efficient and Safe in Comparison to Lipicure^® in Treating Hyperlipidemia

Abstract

Atorvastatin calcium (AC) is a second-generation 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor approved for clinical use as a lipid lowering agent. AC, the world's best selling drug is associated with poor oral bioavailability and serious adverse effects like rhabdomyolysis on chronic administration. A biodegradable nanoparticulate approach was introduced here with a view to improving the efficacy and safety of AC. Poly lactide-co-glycolic acid (PLGA) nanoparticles containing atorvastatin calcium were prepared using two stabilizers i.e. didodecyl dimethyl ammonium bromide (DMAB) and Vitamin E tocopheryl polyethylene glycol 1000 succinate (Vit E-TPGS) using a co-solvent approach by emulsion-diffusion-evaporation method. AC loaded PLGA nanoparticles prepared using DMAB and Vit E-TPGS were found to be 120.0 +/- 4.2 nm and 140.0 +/- 1.5 nm (z-average) in size respectively. In vitro release studies at pH 7.4 revealed a zero order release profile for nanoparticles. Efficacy and safety parameters of the prepared nanoparticles against marketed formulation were evaluated in high fat diet fed (hyperlipidemic) rats. It was found that atorvastatin calcium nanoparticles were equally effective in comparison to Lipicure, at a 66%-reduced dose in treating the hyperlipidemia characterized by alterations in PTC, LDL-C, VLDL-C, HDL-C, PTG and PGL in the high fat diet fed rats. On the other hand, when evaluated for safety, nanoparticulate formulation showed no/negligible myotoxicity characterized by lower PC, BUN, CK, LDH and AST levels in comparison to the marketed formulation.

Biochemical and histopathological assessment of atorvastatin-loaded nanoemulsion effectiveness in Rats

“…26 Atorvastatin has pleiotropic effect through insulin sensitization as it reduces the glucose levels to some extent. 5 In the present study, the 10%ATV-LNE and 20%ATV-LNE groups reduced serum glucose levels compared to all groups especially ATV-Sol groups. In contrast, the serum insulin levels showed no significant differences between all studied groups excepting Blank-NE group showed an increase compared to normal and 20% ATV-LNE groups.…”

“…Meena reported a similar result induced by lipicure nanoparticles formulations. 5 Histopathological examination of kidney from untreated HFD-fed group showed damage of some renal corpuscles and congestion of some glomerular capillaries as well as tubular affection. These findings were supported by those of Ayoub who reported that HFD increased blood glucose, insulin and disturbed the lipid profile.…”

“…25 These results were in agreement with those of Meena who reported that treatment with commercial formulation of atorvastatin calcium (Lipicure) and Poly lactideco-glycolic acid (PLGA) nanoparticles formulations had shown almost equal effects in reducing levels of CHO, TG, LDL-C and elevated HDL-C levels. 5 Nanoparticles have been reported to increase the absorption of the encapsulated drugs when compared to the suspension form or any simple formulation type of the drug. 26 Atorvastatin has pleiotropic effect through insulin sensitization as it reduces the glucose levels to some extent.…”

“…The results obtained were similar to those results of a study done by Meena who declared that treatment with commercial formulation (Lipicure®) showed an increase in AST levels in hyperlipidemic rats. 5 Furthermore, several studies reported that treatment with lipitor commercial formulation cause an elevation in ALT and AST activities more than 3X upper normal limits. 28 Although statins appear safe, animal and pre-marketing clinical trials are shown signs of liver toxicity, mostly manifesting as minor elevations in aminotransferase concentrations.…”

“…4 Atorvastatin (ATV) is the leading drug among statins. 5 The oral absorption of ATV is 30% and bioavailability is only 12%. 6 As with other HMG-CoA reductase inhibitors, the most frequently reported adverse events associated with ATV are gastrointestinal effects.…”