title: 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.
authors.affiliation: Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Phase-X, S A S Nagar, Punjab 160062, India.
authors.forename: A K
authors.initials: AK
authors.lastname: Meena
authors.forename: D Venkat
authors.initials: DV
authors.lastname: Ratnam
authors.forename: G
authors.initials: G
authors.lastname: Chandraiah
authors.forename: D D
authors.initials: DD
authors.lastname: Ankola
authors.forename: P Rama
authors.initials: PR
authors.lastname: Rao
authors.forename: M N V Ravi
authors.initials: MN
authors.lastname: Kumar
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D000069059:Atorvastatin; D001786:Blood Glucose / Q000032:analysis; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D006538:Heptanoic Acids / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D006949:Hyperlipidemias / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D019344:Lactic Acid; D008055:Lipids / Q000097:blood; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011758:Pyrroles / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000924:Anticholesteremic Agents; D001786:Blood Glucose; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D011758:Pyrroles; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D002784:Cholesterol; D000069059:Atorvastatin; D006903:Hydroxymethylglutaryl CoA Reductases