A Self-Nanoemulsifying Drug Delivery System for Vitamin D3: Design, Optimization and Pharmacokinetic Evaluation

Vitamin D3 (VTD3), a fat-soluble vitamin, is vital for various physiological functions but suffers from poor stability and solubility. Formulation strategies are essential to enhance its stability and bioavailability. This study aimed to develop an optimized Self-Nanoemulsifying Drug Delivery System (SNEDDS) for VTD3 to improve its dissolution efficiency and systemic availability via oral administration using a Design of Experiments (DoE) approach.

Solubility and emulsification studies identified suitable oils, surfactants, and cosurfactants. Ternary phase diagrams and a simplex lattice design were employed to optimize the formulation. Captex 300 (X1), Acrysol K 140 (X2), and Transcutol HP (X3) were the independent variables, while droplet size (Y1) and cumulative drug release (Y2) in pH 1.2 HCl were the dependent variables. The final formulation was selected based on desirability functions, and contour and surface plots were applied for detailed analysis. The SNEDDS was evaluated for visual inspection, globule size, zeta potential, emulsification time, PDI, cloud point, resistance to dilution, VTD3 content, drug release, stability, and pharmacokinetic properties.

The optimized SNEDDS (20% Captex 300, 50% Acrysol K140, 30% Transcutol HP) exhibited a globule size of 18.22 nm, > 98% drug content, and > 86% drug release within 60 min in both 0.1 N HCl and pH 6.8 buffer. A 3.95-fold bioavailability improvement was observed in vivo compared to plain VTD3 suspension. Stability studies confirmed no significant changes in the physicochemical properties.

The developed SNEDDS formulation, encapsulated in HPMC capsules, significantly improved VTD3's stability, dissolution, and bioavailability. This provides a promising approach to oral lipophilic compound delivery.