European Journal of Biomedical and Pharmaceutical Sciences

NANOSTRUCTURED LIPID CARRIER – A NOVEL DOSAGE FORM TO IMPROVE THE ORAL BIOAVAILABILITY OF LOPINAVIR

Kaushal P. Patel*, Chirayu J. Pathak and Dr. Rakesh P. Patel

ABSTRACT

Lopinavir (LPV) is used in combined chemotherapy which is also known as Highly Active Anti-Retroviral Therapy (HAART). It is a potent and one of the frequently administered protease inhibitors used in the therapeutic treatment of the HIV. LPV has very poor oral bioavailability which is due to P-glycoprotein efflux transport and high first pass metabolism primarily mediated by cytochrome P450. LPV is given in combination with Ritonavir (RTV) in most of the marketed formulation due to its high first pass metabolism because RTV inhibits or suppress the cytochrome P450 enzyme. On the other hand, LPV and RTV combination therapy leads to major adverse effects such as Perioral Parasthesias, Elevations of lipid level, Glucose as well as Gastrointestinal intolerance. Hence, there is a need of a RTV free formulation strategy to improve the oral bioavailability of LPV. Nanostructured Lipid Carriers (NLCs) of LPV were prepared using High Speed Homogenization. LPV were successfully encapsulated in the lipid mixture of Glyceryl Behenate & Miglyol 812 by using Poloxamer 188 as a surfactant. Quality target product profile was achieved by using optimized formulation as well as process parameter. Optimized formulation have mean particle size <200 nm with Polydispersity index around 0.1 which indicates very narrow particle size distribution. Entrapment efficiency was around 90 %. Slow drug release profile indicates the homogeneous dispersion of LPV in lipid matrix. TEM image of the LPV loaded NLCs indicates that NLCs have spherical feature with better uniformity. Also they are not aggregated. Absence of characteristic & intense peaks of LPV in NLCs indicates presence of LPV in more amorphous form and efficient miscibility of LPV in lipids. This further proves presence of molecular level dispersion of drug in lipid matrix after NLCs formation which results in the crystalline reduction of drug and lipid. Also there is no significant change upon the Stability. For LOP-NLCs, the AUC was found to be around 280 % than LOP Solution. This bioavailability increment indicates higher GI uptake of LOP-NLC in comparison to LOP solution. In a nutshell, Nanoformulation such as Nanostructured Lipid Carrier is one of the promising approach to enhance the Oral Bioavailability of LPV.

Keywords: Lopinavir (LPV), Nanostructured Lipid Carrier (NLCs), Encapsulated, Homogeneous Dispersion, Oral Bioavailability.