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

  • Original Article
  • Published:
Lipids

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.

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Abbreviations

AC:

Atorvastatin calcium

AST:

Aspartate amino transferase

BUN:

Blood urea nitrogen

PTC:

Plasma total cholesterol

PTG:

Plasma triglyceride

LDL-C:

Low-density lipoprotein cholesterol

HDL-C:

High-density lipoprotein cholesterol

VLDL-C:

Very low-density lipoprotein cholesterol

CK:

Creatinine kinase

LDH:

Lactate dehydrogenase

PC:

Plasma creatinine

NPD:

Normal pellet diet

HFD:

High fat diet

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Acknowledgments

AKM acknowledges a NIPER MS fellowship. Financial support in the form of a research grant (IR/SO/LF-03/2006) from the Department of Science and Technology (DST), Government of India, is gratefully acknowledged. Authors acknowledge Mr. Vijender Singh Beniwal for the AFM studies.

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Authors and Affiliations

  1. Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Phase-X, S. A. S. Nagar, Punjab, 160062, India

    A. K. Meena, D. Venkat Ratnam, D. D. Ankola & M. N. V. Ravi Kumar

  2. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Phase-X, S. A. S. Nagar, Punjab, 160062, India

    G. Chandraiah & P. Rama Rao

  3. Center for Pharmaceutical Nanotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Phase-X, S. A. S. Nagar, Punjab, 160062, India

    G. Chandraiah, D. D. Ankola, P. Rama Rao & M. N. V. Ravi Kumar

Authors
  1. A. K. Meena
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  2. D. Venkat Ratnam
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  3. G. Chandraiah
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  4. D. D. Ankola
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Correspondence to M. N. V. Ravi Kumar.

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Meena, A.K., Ratnam, D.V., Chandraiah, G. et al. Oral Nanoparticulate Atorvastatin Calcium is More Efficient and Safe in Comparison to Lipicure® in Treating Hyperlipidemia. Lipids 43, 231–241 (2008). https://doi.org/10.1007/s11745-007-3142-5

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  • DOI: https://doi.org/10.1007/s11745-007-3142-5

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