Atorvastatin-Loaded Oleic Acid Nanoglobules for Oral Administration: In Vitro Characterization and Biopharmaceutical Evaluation

Pradum Pundlikrao      Ige; Nilesh Ashok      Bachhav; Hitendra Shaligram      Mahajan; Pankaj Padmakar      Nerkar; Surendra Ganeshlal      Gattani

doi:10.2174/1573413711309020007

Abstract

Poorly water-soluble drugs like atorvastatin with low bioavailability needs novel approach for enhancement of bioavailability and therapeutic efficacy. The use of nanotechnology to formulate as nanoemulsions offer an opportunity to address the issues associated with BCS class II drugs. Nanoemulsion of atorvastatin was developed by spontaneous emulsification method with the aim of enhancing the solubility and oral bioavailability of atorvastatin. Pseudo ternary phase diagrams were constructed to identify the nanoemulsion region. The desired formulations of nanoemulsion region were developed and characterized by globule size, scanning electron microscopy, partition coefficient, clarity, viscosity, percent drug entrapment efficiency, in vitro drug release and in vivo pharmacodynamic studies. The release of drug from nanoemulsion had significantly higher (p ‹ 0.01) as compared to the pure drug. The optimized formulation code NE3 containing 5% Oleic acid, 20% [Cremophore EL: ethanol (1:1)], and 75% of aqueous phase had enhanced solubility from 41.8 ± 2.45 to 69.07 ± 1.41. Globule size and zeta potential of the optimized nanoemulsion formulation were found to be 153.9 ± 1.02 nm and – 32.9 mV, respectively. Biopharmaceutical evaluation of the optimized nanoemulsion formulation was performed by a triton–induced hypercholesterolemia model in male albino wistar rats. The optimized nanoemulsion showed significantly reduced serum lipid levels as compared to pure atorvastatin. In conclusion, the developed nanoemulsion could be an alternative for the enhancement of solubility and bioavailability for the oral drug delivery in management of atherosclerosis.

Keywords: Atorvastatin, in vivo pharmacodynamic studies, nanoemulsion, polydispersity index, pseudo ternary phase diagram, solubility enhancement, titration method, zeta potential.