Development and Evaluation of Nanostructured Lipid Carriers for Enhanced Oral Bioavailability of Poorly Soluble Antihypertensive Drugs

Abstract

Low aqueous solubility and low bioavailability in the oral route are major hurdles that many antihypertensive drugs face, which result in poor therapeutic activity. In this study, an attempt was made to develop and characterize Nanostructured Lipid Carriers (NLCs) in order to enhance the oral bioavailability of a BCS Class II antihypertensive drug. NLCs were formulated by using the hot melt homogenization method by using solid lipid, liquid lipid, and surfactant. Formulations were optimized using Box-Behnken design having particle size, entrapment efficiency, and drug release as the dependent variables. The optimized NLC formulation displayed particle size of 142.3 nm, zeta potential of -28.6 mV and entrapment efficiency of 88.4%. The in-vitro drug release studies showed sustained release with a maximum of 85% drug release within 24 hours when compared with only 32% of the drug released in case of the pure drug suspension. Ex-vivo permeability study using rat intestinal sac also demonstrated that the drug release was increased 3.2 folds in case of the NLC formulation. Pharmacokinetic study conducted on Wistar rats indicated that there was a 4.1 fold increase in Cmax and 3.8 fold increase in AUC when compared to the conventional tablet. Results of stability testing performed at 25°C/60% RH and 40°C/75% RH for 3 months proved that there is no significant change in the physicochemical parameters of the formulation. SEM and DSC study indicated successful loading and amorphous state of the drug in NLCs. Hence it was found out that the formulation could significantly enhance solubility, permeability and bioavailability of the poorly water soluble antihypertensive drugs.