Optimizing the formulation variables for encapsulation of linezolid into polycaprolactone inhalable microspheres using double emulsion solvent evaporation

Abstract

Inhaled antibiotics delivered through dry powder inhalers (DPIs) effectively treat severe bacterial infections by directly targeting the lungs. Our study focused on developing inhalable dry powder microspheres of linezolid (LNZ) using biodegradable polycaprolactone (PCL) polymer. The LNZ-PCL microspheres were fabricated using a double emulsification solvent evaporation method. Optimization of formulation parameters was performed using a factorial design. Evaluation of the microspheres included size, shape, drug loading, entrapment efficiency, aerosolization, and drug release. The morphological analysis confirmed spherical-shaped rough particles within the inhalable size range. The encapsulation efficiency was determined to be 52.84%, indicating successful drug incorporation. Aerosolization efficiency was significantly enhanced when LNZ-PCL microspheres were combined with lactose as a carrier, achieving a fine particle fraction (FPF) value of 70.90%. In-vitro dissolution studies demonstrated sustained drug release for over 24 h under lung pH conditions. Overall, our study highlights the potential of inhalable LNZ-PCL microspheres as a targeted approach for treating pulmonary tuberculosis. Further research and in-vivo studies are needed to validate their effectiveness in life-threatening bacterial infections.