Enhancement of Solubility and Oral Bioavailability of Nintedanib Snedds

Objective: The present study aimed to develop a Self-Nanoemulsifying Drug Delivery System (SNEDDS) of Nintedanib, a BCS Class II drug, to improve its solubility, dissolution, and oral bioavailability. Methods: Solubility studies of Nintedanib were carried out in various oils, surfactants, and co-surfactants. Based on maximum solubility, Captex 200, Solutol HS15, and PEG 600 were selected as oil, surfactant, and co-surfactant, respectively. Different Smix ratios (1:1, 2:1, 3:1, and 4:1) were prepared and used for SNEDDS formulation development. The optimized formulation was characterized for droplet size, zeta potential, and surface morphology using scanning electron microscopy (SEM). In vitro dissolution and in vivo pharmacokinetic studies were also performed. Results: The optimized formulation (F13) exhibited a droplet size of 76.2 nm, a polydispersity index (PDI) of 0.214±0.015, and a zeta potential of −12.4 mV. SEM analysis confirmed the spherical morphology of the nanoemulsion droplets. In vitro dissolution studies demonstrated a maximum drug release of 99.92% within 60 min, compared with 31.98% for the pure drug. The optimized formulation remained stable for six months under accelerated storage conditions. In vivo pharmacokinetic studies demonstrated a 2.15-fold increase in Cmax and a 2.49-fold increase in AUC₀–t compared with the pure drug suspension, indicating enhanced systemic exposure and improved relative oral absorption of the SNEDDS formulation. Conclusion: The developed Nintedanib SNEDDS significantly enhanced solubility, dissolution rate, and oral bioavailability of the poorly soluble drug. The in vitro and in vivo results confirmed the potential of SNEDDS as an effective nanocarrier system for improving the therapeutic performance of Nintedanib.