Optimized tolterodine tartrate loaded SNEDDS for enhanced oral bioavailability: In vitro and in vivo studies

The study investigated tolterodine tartrate (TOT)-loaded optimized SNEDDS for improved stability, facilitated absorption, and high oral bioavailability (BA). The QbD-approach optimized the robust composition and identified the impact of critical factors (olive oil = X₁ and cremophor EL = X₂) on the set responses (Y₁ = size, Y₂ = %Transmittance, and Y₃ = % entrapment efficiency). Thermodynamic stability testing was conducted under stressed conditions. The optimized SNE-TOT2 was evaluated for the formulation characteristics (size distribution, shape, and zeta potential), followed by comparative in vitro drug release and ex vivo intestinal permeation studies. In vitro hemolysis study surrogated acute preliminary toxicity study. Oral pharmacokinetics and hepatotoxicity studies were performed in rats under fast condition. The thermodynamically stable SNE-TOT2 (desirability ∼ 0.97) possessed desired formulations attributes (small size, 159 nm; low polydispersity index, 0.235; high zeta potential, −16.54 mV; high %EE, 81 %, and high %transmittance) and efficient self-emulsification performance. The impact of X₁ and X₂ on Y₁-Y₃ was quadratic, indicating the need for optimal selection of these factors. SNE-TOT2 showed anomalous (non-Fickian) drug release behavior (> 80 % within 15 min) and as compared to SUS-TOT. SNE-TOT2 exhibited the highest intestinal permeation (219.9 ± 27.21 μg/cm²), suggesting superior absorption compared with SUS-TOT (59.2 ± 13.9 μg/cm²) and marketed (MKT-TOT) (128.2 ± 23.18 μg/cm²). Moreover, SNE-TOT2 improved pharmacokinetic parameters and reduced hepatic toxicity, compared to SUS-TOT and MKT-TOT. Thus, SNE-TOT2 can be a promising and safe oral product with improved oral BA.