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

• Published in: European journal of pharmaceutical sciences Vol. 138; p. 105028
• Main Authors: Nurbaeti, Siti Nani, Brillault, Julien, Tewes, Frédéric, Olivier, Jean-Christophe
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-10-2019; Elsevier
• Subjects: Administration, Inhalation; Aerosol; Aerosols; Aerosols - chemistry; Antimicrobial; Chloramphenicol; Chloramphenicol - analogs & derivatives; Chloramphenicol - chemistry; Delayed-Action Preparations; Delayed-Action Preparations - chemistry; Drug Carriers; Drug Carriers - chemistry; Drug Compounding; Drug Compounding - methods; Dry Powder Inhalers; Dry Powder Inhalers - methods; Emulsions; Emulsions - chemistry; Excipients; Excipients - chemistry; Life Sciences; Lung; Lung - metabolism; Lung delivery; Microscopy, Electron, Scanning; Microscopy, Electron, Scanning - methods; Nanoparticles; Nanoparticles - chemistry; Palmitate prodrug; Particle Size; Pharmaceutical sciences; PLGA; Powders; Powders - chemistry; Prodrugs; Prodrugs - chemistry; Thiamphenicol; Thiamphenicol - chemistry; Antimicrobial; PLGA; Aerosol; Lung delivery; Chloramphenicol; Palmitate prodrug; Thiamphenicol
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2019.105028

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.
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