Quality by Design Approach for Formulation and Evaluation of Spray-Dried Powders Containing Nano-in-Microparticles for the Treatment of COPD

Fluticasone propionate (FP) NIMs produced with spray drying technology have been developed and assessed in vivo in this work in order to deliver the drug directly to the lungs. Using the quality by design (QbD) approach, chitosan (CS) NIMs loaded with FP have been developed by spray drying. To forecast the ultimate product quality, QbD, a modern regulatory-based quality management technique, was employed. Mannitol and leucine have been used as the deaggregating agent and to enhance aerosolization behavior, respectively. The impact of three variables, polymer content, inlet temperature and feed flow rate check, on quality parameters, such as particle size and entrapment efficiency, was determined based on risk assessment. A Box-Behnken design was applied for further optimization. The formulated compounds underwent characterization for physical attributes employing differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). Additionally, in vitro assessments, X-ray diffraction analyses and in vitro deposition evaluations were conducted utilizing a cascade impactor. In accordance with the QbD paradigm, the design space (DS) was meticulously refined through the integration of chosen variables, achieving an entrapment efficiency exceeding 50% w/w, alongside a particle size range of 800–4000 nm. The inlet temperature and polymer concentration had the greatest effects on the particle size. In vitro drug release followed initial burst release around 20.26% in 3–4 h with sustained drug release of 98.43% NIMs emitted 36–45% respirable fraction, indicating deep targeting of FP to the pulmonary. Lung histopathological studies proved the tissue compatibility of formulations to be safe and effective.