Send Orders of Reprints at reprints@benthamscience.net 202 Current Nanoscience, 2013, 9, 202-210 Atorvastatin-Loaded Oleic Acid Nanoglobules for Oral Administration: In Vitro Characterization and Biopharmaceutical Evaluation Pradum Pundlikrao Ige* 1 , Nilesh Ashok Bachhav 1 , Hitendra Shaligram Mahajan 1 , Pankaj Padmakar Nerkar 1 and Surendra Ganeshlal Gattani 2 1 Department of Pharmaceutics and Quality Assurance, R C Patel Institute of Pharmaceutical Education and Research, Shirpur, Dhule, Maharashtra 425405, India; 2 School of Pharmacy, Swami Ramanand Teerth Marathwada University, Vishnupuri, Nanded, Maharashtra, 431606, India 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 re- gion. 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 hy- percholesterolemia 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. INTRODUCTION According to Biopharmaceutical classification system (BCS) - class II drugs show the low solubility and consequently low bioavailability. On the basis of BCS, different strategies can be attempted to increase the solubility of drug; either by increasing amount of dissolved drug i.e. in contact with the absorbing mem- brane or increasing the permeability of the membrane. The BCS class II drugs, having limited dissolution but no limited permeation. Hence, there is need to increase the amount of dissolved drug at the absorption site and it is proven to be effective in many studies [1, 2]. Various techniques have been developed to enhance the solubil- ity of poorly-soluble drugs [3-6]. Nanotechnology comprises technological developments on the nanometer scale, usually 0.1-200 nm. The use of nanotechnology in pharmaceuticals and medicine has grown over the last few years. The various nanopharmaceuticals are currently being used. Some nanopharmaceuticals are in the process of development are nanoe- mulsions, nanosuspensions, nanospheres, nanotubes, nanoshells, nanocapsules, solid lipid nanoparticles and dendrimers. Nanoemul- sions are the group of dispersed globules used for pharmaceutical, biomedical aids and vehicles that show great promise for the future of cosmetics, diagnostics, drug therapies and biotechnologies [7- 11]. Nanoparticles can exist in W/O and O/W forms and the core of the globule is either water or oil and vice-versa. Nanoemulsions are prepared by the spontaneous emulsification method i.e. titration *Address correspondence to this author at the Department of Pharmaceutics & Quality Assurance, R.C. Patel Institute of Pharmaceutical Education & Research, Karwandnaka, Shirpur, Dhule, Maharashtra, 425405, India; Tel: +91-2563-255189; Mobile: +91-9823509648; Fax: +91-2563-252808; E-mail: pradyumna_1978@rediffmail.com method. It can be prepared by using a blend of oil, water, surfac- tant, and co-surfactant in the optimum at mild agitation. The orders of mixing of the components are generally considered not too criti- cal since nanoemulsions are formed spontaneously. Although nanoemulsification is a spontaneous process, the driving forces are small and the time to reach the equilibrium can be long [12]. Nanoemulsions are colloidal nanodispersions of O/W or W/O and thermodynamically stabilized by an interfacial film of surfac- tant(s) and cosurfactant(s). Hence, it has revealed tremendous po- tential in the nanoengineering of various inorganic materials [13, 14]. Lipid-based formulation approach has been attracted wide attention in the context of improving the oral bioavailability of low water-soluble drugs and delivering the drug at a target site. The most popular approach is the incorporation of the active lipophilic component into inert lipid vehicles such as oils, surfactant disper- sions, self nano or microemulsifying formulations, solid emulsions, and liposomes [15-17]. The drug can be loaded into the inner phase and delivered by lymphatic route, for bypassing enzymes in the gastrointestinal tract (GIT) and reducing presystemic clearance and hepatic first pass metabolism. Nanoemulsions had many advantages like higher drug solubilization capacity, better thermodynamic stability, long shelf- life, rapid onset of action and reduced inter subject variability which make them a promising technology to achieve optimum tar- geted drug delivery [18, 19]. Mechanistically, drug is partitioned between dispersed and continuous phase in nanoemulsion, when the system comes into contact with semipermeable membrane, the drug can be transported through barrier due to enhanced permeability [20]. The nanosized droplets or globules lead to enormous interfa- cial area and would influence the transport properties of the drug and this remains crucial parameter for enhancement of bioavailabil- ity [21, 22]. 1875-6786/13 $58.00+.00 © 2013 Bentham Science Publishers