Design and Characterization of Nanostructured Lipid Carrier of Poorly Water Soluble Drug for Improvement of Bioavailability

Abstract

: Oxaprozin is a nonsteroidal anti-inflammatory drug (NSAID) belonging to the Biopharmaceutics Classification System (BCS) Class II, characterized by poor aqueous solubility despite high permeability. Its limited water solubility results in a slow dissolution rate, delayed onset of action, and reduced oral bioavailability, which can compromise its therapeutic efficacy. Therefore, developing an effective drug delivery system to enhance the solubility and bioavailability of oxaprozin remains an important pharmaceutical challenge. The present study aimed to design and characterize a nanostructured lipid carrier (NLC) formulation of oxaprozin to improve its solubility, dissolution behavior, and oral bioavailability. Nanostructured lipid carriers were developed using a blend of solid and liquid lipids stabilized with suitable surfactants through high-shear homogenization followed by ultrasonication. The formulation variables were optimized to obtain nanoparticles with desirable physicochemical properties and high drug encapsulation. The prepared NLCs were comprehensively characterized for particle size, polydispersity index (PDI), zeta potential, drug loading, entrapment efficiency, morphology, thermal behavior, crystallinity, and in vitro drug release. The optimized formulation exhibited nanosized particles with a narrow size distribution, high encapsulation efficiency, and acceptable zeta potential, indicating good physical stability. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analyses confirmed the successful incorporation of oxaprozin into the lipid matrix with a reduction in its crystalline nature, contributing to improved drug solubility. In vitro dissolution studies demonstrated a significantly enhanced drug release profile from the optimized NLC formulation compared with pure oxaprozin, owing to the increased surface area and partial amorphization of the drug within the lipid matrix. The sustained release characteristics of the NLCs further suggested their potential to maintain therapeutic drug concentrations over an extended period. Pharmacokinetic evaluation indicated that the optimized NLC formulation improved the oral bioavailability of oxaprozin by enhancing its dissolution rate and intestinal absorption. The lipid-based nanocarrier system also has the potential to facilitate lymphatic transport and reduce first-pass metabolism, thereby improving systemic drug exposure. Overall, the findings of this study demonstrate that nanostructured lipid carriers are a promising and effective approach for enhancing the solubility, dissolution, and oral bioavailability of poorly water-soluble oxaprozin. The developed formulation may improve therapeutic efficacy while reducing dose-related variability, making NLCs a suitable delivery platform for oxaprozin and other poorly water-soluble drugs.