Oral nanoparticulate atorvastatin calcium is more efficient and safe in comparison to Lipicure® in treating hyperlipidemia

A. K. Meena, D. Ratnam, G. Chandraiah, D. D. Ankola, Rama. P. Rao, M.N.V. Ravi Kumar

Research output: Contribution to journalArticle

27 Citations (Scopus)

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.
LanguageEnglish
Pages231-241
Number of pages10
JournalLipids
Volume43
Issue number3
DOIs
Publication statusPublished - 10 Jan 2008

Fingerprint

Hyperlipidemias
glycolic acid
Nanoparticles
High Fat Diet
Succinic Acid
Nutrition
Vitamin E
Safety
Rats
Fats
Hydroxymethylglutaryl CoA Reductases
Rhabdomyolysis
Factor IX
Blood Urea Nitrogen
Emulsions
Biological Availability
Atorvastatin Calcium
Sales
Evaporation
Lipids

Keywords

  • bioavailability
  • hyperlipidemia
  • nanoparticles
  • oral delivery
  • rhabdomyolysis

Cite this

Meena, A. K., Ratnam, D., Chandraiah, G., Ankola, D. D., Rao, R. P., & Kumar, M. N. V. R. (2008). Oral nanoparticulate atorvastatin calcium is more efficient and safe in comparison to Lipicure® in treating hyperlipidemia. Lipids, 43(3), 231-241. https://doi.org/10.1007/s11745-007-3142-5
Meena, A. K. ; Ratnam, D. ; Chandraiah, G. ; Ankola, D. D. ; Rao, Rama. P. ; Kumar, M.N.V. Ravi. / Oral nanoparticulate atorvastatin calcium is more efficient and safe in comparison to Lipicure® in treating hyperlipidemia. In: Lipids. 2008 ; Vol. 43, No. 3. pp. 231-241.
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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{\circledR}, 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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Oral nanoparticulate atorvastatin calcium is more efficient and safe in comparison to Lipicure® in treating hyperlipidemia. / Meena, A. K.; Ratnam, D.; Chandraiah, G.; Ankola, D. D.; Rao, Rama. P.; Kumar, M.N.V. Ravi.

In: Lipids, Vol. 43, No. 3, 10.01.2008, p. 231-241.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Oral nanoparticulate atorvastatin calcium is more efficient and safe in comparison to Lipicure® in treating hyperlipidemia

AU - Meena, A. K.

AU - Ratnam, D.

AU - Chandraiah, G.

AU - Ankola, D. D.

AU - Rao, Rama. P.

AU - Kumar, M.N.V. Ravi

PY - 2008/1/10

Y1 - 2008/1/10

N2 - 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.

AB - 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.

KW - bioavailability

KW - hyperlipidemia

KW - nanoparticles

KW - oral delivery

KW - rhabdomyolysis

UR - http://dx.doi.org/10.1007/s11745-007-3142-5

U2 - 10.1007/s11745-007-3142-5

DO - 10.1007/s11745-007-3142-5

M3 - Article

VL - 43

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EP - 241

JO - Lipids

T2 - Lipids

JF - Lipids

SN - 0024-4201

IS - 3

ER -