LAUSR

Graphical abstract Figure. No Caption available. ABSTRACT The aim of this study was to develop polyunsaturated fatty acid (PUFA) long chain glyceride (LCG) enriched self‐nanoemulsifying lipidic nanomicelles systems (SNELS) for augmenting lymphatic uptake and enhancing oral bioavailability of docetaxel and compare its biopharmaceutical performance with a medium‐chain fatty acid glyceride (MCG) SNELS. Equilibrium solubility and pseudo ternary phase studies facilitated the selection of suitable LCG and MCG. The critical material attributes (CMAs) and critical process parameters (CPPs) were earmarked using Placket‐Burman Design (PBD) and Fractional Factorial Design (FFD) for LCG‐ and MCG‐SNELS respectively, and nano micelles were subsequently optimized using I‐ and D‐optimal designs. Desirability function unearthed the optimized SNELS with Temul <5 min, Dnm <100 nm, Rel15min >85% and Perm45min > 75%. The SNELS demonstrated efficient biocompatibility and energy dependent cellular uptake, reduced P‐gp efflux and increased permeability using bi‐directional Caco‐2 model. Optimal PUFA enriched LCG‐SNELS exhibited distinctly superior permeability and absorption parameters during ex vivo permeation, in situ single pass intestinal perfusion, lymphatic uptake and in vivo pharmacokinetic studies over MCG‐SNELS.