Sustained-release microparticle dry powders of chloramphenicol palmitate or thiamphenicol palmitate prodrugs for lung delivery as aerosols

The purpose of this study was to design inhalable sustained-release nanoparticle-in-microparticles, i.e. nano-embedded microparticles, for the lung delivery of chloramphenicol or thiamphenicol as aerosols. The palmitate ester prodrugs of the two Antibiotics were used to prepare PLGA-based nanoparticles or to form pure prodrug nanoparticles. Prodrug-loaded PLGA nanoparticles or pure prodrug nanoparticles were prepared using the emulsion-solvent evaporation method. Dry microparticle powders for inhalation were then produced by spray-drying the nanoparticle suspensions supplemented with lactose as a bulking agent and L-leucine as a dispersing enhancer. Examined under the scanning electron microscopy, the obtained microparticles appeared to be spherical and shriveled, with no crystal-like structures. Drug loading was satisfactory (14 to 34% (m/m)) and the aerodynamic properties determined with a Next Generation Impactor were appropriate for lung delivery, with mass median aerodynamic diameters close to 3 μm. The in vitro release profiles showed that sustained released was achieved with these formulations, with an almost complete release over 14 days.