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 direct to the lungs. Using the quality by design (QbD) approach, chitosan (CS) NIMs loaded with fluticasone propionate (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 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 particle size and entrapment efficiency were determined based on risk assessment. 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 Quality by Design (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 to 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 to 4 h with sustained drug release of 98.43 % NIMs emitted 36 to 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.