Quality by design (QbD)-driven formulation of sildenafil citrate microparticles using quasi-emulsion technique for pulmonary delivery: an in vitro study.

Objective: The goal of this research was to create inhalable microparticles to ensure the continuous delivery of sildenafil citrate (SC) to treat pulmonary arterial hypertension (PAH). This was done to address the limitations of SC, including its short half-life and systemic side effects.

Methods: To create the inhalable microparticles, a particle engineering method called the quasi-emulsion solvent diffusion method was utilized. The study employed quality by design (QbD), a regulatory-based approach, to enhance the final product's quality. The optimization of microparticles was achieved using central composite design to enhance micromeritics properties and sustain drug release profiles. Characterization studies, including FTIR, differential scanning calorimetry (DSC), scanning electron microscopy, XRD, and surface morphology analysis, were conducted to evaluate the microparticles. Aerodynamic properties were measured to predict where particles will be deposited in the respiratory tract.

Results: The optimized formulated microparticles had an acceptable mean particle size and an entrapment efficiency greater than 90%. The optimized microparticles demonstrated a sustained drug release of 80.42 ± 0.23% over 24 h. Aerodynamic properties showed a mass median aerodynamic diameter of 3.45 ± 0.0 µm, a fine particle fraction of 21%, and 77.29 ± 2.9% of the dose recovered from the inhaler. Modified tapped density measurements indicated improved flow properties of the microparticles.

Conclusion: The QbD approach was successfully employed to formulate inhalable microparticles for sustained pulmonary delivery. The optimized microparticles exhibited enhanced micromeritics properties and sustained drug release profiles, making them a promising option for the treatment of PAH.