Design, Optimization And In-Vitro–Ex-Vivo Evaluation Of Enteric-Coated Nanocarriers For Enhanced Oral Bioavailability Of A Poorly Soluble Drug

Abstract

The present study aimed to design, optimize, and evaluate enteric-coated nanocarriers to enhance the oral bioavailability of Rifaximin, a poorly soluble and P-glycoprotein–susceptible drug. Preformulation studies, including organoleptic assessment, solubility profiling, FTIR, DSC, partition coefficient, hygroscopicity analysis, and micromeritic evaluation, confirmed the physicochemical suitability and compatibility of Rifaximin with glyceryl monostearate, Pluronic F68, and Eudragit L100. Solid lipid nanoparticles were prepared using a solvent-injection method and subsequently coated to obtain enteric-protected RFN-EC-SLNs. A Quality-by-Design–enabled Box–Behnken Design (BBD) was employed by varying lipid concentration, surfactant level, and polymer content to optimize critical quality attributes: particle size, entrapment efficiency, and drug release. Statistical modeling revealed significant effects of lipid and polymer levels on nanoparticle characteristics, and the optimized formulation (F6) achieved a particle size of 154 ± 14 nm, entrapment efficiency of 82 ± 0.9%, and drug release of 86 ± 1.2%.

In-vitro release studies demonstrated effective gastric protection at pH 1.2 and sustained intestinal release at pH 6.8, confirming the enteric functionality of Eudragit L100. Ex-vivo permeation across sheep intestinal mucosa showed enhanced permeation and reduced efflux, indicating improved trans-epithelial transport and P-gp modulation. Stability studies conducted under ICH conditions established the robustness, physicochemical stability, and retention of functional properties of the optimized formulation. Overall, the developed enteric-coated nanocarriers significantly improved the solubility, intestinal release, and permeation profile of Rifaximin, supporting their potential as an effective oral delivery platform for poorly soluble drugs.