Quality-by-Design-Based Development and Optimization of Emtricitabine-Loaded Solid Lipid Nanoparticles

Background: Emtricitabine (FTC) is a nucleoside reverse transcriptase inhibitor widely used in combination antiretroviral therapy for HIV infection. Its pharmacokinetic characteristics and need for regular dosing may affect patient adherence. Solid lipid nanoparticles (SLNs) have been considered beneficial in terms of drug entrapment and drug delivery. The study was conducted using a Quality-by-Design (QbD) strategy along with Box–Behnken Design (BBD) in order to optimize FTC-loaded SLNs systematically. Methods: A three-variable, three-level Box-Behnken Design consisting of seventeen runs has been employed to investigate the effects of stearic acid concentration, Tween 80 concentration, and homogenization speed on the entrapment efficiency of FTC. Results: The optimized quadratic model exhibited exceptional predictive ability (R² =0.9989, adjusted R² = 0.9976, predicted R² = 0.9867), along with a non-significant lack of fit (p = 0.1047). It was found that stearic acid had the highest positive effect on EE%, while an increase in Tween 80 concentration and homogenization speed reduced the drug entrapment significantly. Results from the numerical optimization indicated that the optimized formulation had 164.68 mg of stearic acid, 2.09% of Tween 80 concentration, and a homogenization speed of 12,074.8 rpm, which yielded an EE% of 85.32%. Experimental validation indicated an EE% of 85.28%, which matched quite closely with the predicted value, yielding a prediction bias of 0.047%. Conclusion: The QbD-driven BBD method developed a reliable and statistically valid optimization method for SLNs loaded with FTC. The optimization study provided an effective formulation with high entrapment efficiency and corroborated the reliability of the approach employed, leading to promising possibilities for the physical and chemical characterization, controlled release assessment, and future reproduction of emtricitabine-loaded lipid formulations. Keywords – Emtricitabine[FTC]; Solid lipid Nanoparticles[SLNs]; Quality by Design[QbD]; Entrapment efficiency; Box-Behnken design [BBD]; Nanocarrier optimization.