Dry powder inhaler formulation of high-payload antibiotic nanoparticle complex intended for bronchiectasis therapy: Spray drying versus spray freeze drying preparation

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• 作者：Hong Yu^a ; Jeanette Teo^b ; Jia Wei Chew^a ; Kunn Hadinoto^a ; ^{kunnong@ntu.edu.sg" class="auth_mail" title="E-mail the corresponding author}
• 关键词：COPD ; chronic obstructive pulmonary diseases ; dA ; aerodynamic diameter ; dA ; theory ; theoretical aerodynamic diameter ; dG ; geometric diameter ; DI ; dispersibility index ; DPI ; dry powder inhaler ; DXT ; dextran sulfate ; ED ; emitted dose ; FPF ; fine particle fraction ; IP ; induction port ; PS ; pre-separator ; Leu ; l-leucine ; Man ; d-mannitol ; MHB ; Mueller Hinton broth ; MIC ; minimum inhibitory concentration ; MMAD ; mass median aerodynamic diameter ; n ; number of experimental replicates ; OD600 ; optical density
• 刊名：International Journal of Pharmaceutics
• 出版年：2016
• 出版时间：29 February 2016
• 年：2016
• 卷：499
• 期：1-2
• 页码：38-46
• 全文大小：1700 K

文摘

Inhaled nano-antibiotics have recently emerged as the promising bronchiectasis treatment attributed to the higher and more localized antibiotic exposure generated compared to native antibiotics. Antibiotic nanoparticle complex (or nanoplex in short) prepared by self-assembly complexation with polysaccharides addresses the major drawbacks of existing nano-antibiotics by virtue of its high payload and cost-effective preparation. Herein we developed carrier-free dry powder inhaler (DPI) formulations of ciprofloxacin nanoplex by spray drying (SD) and spray freeze drying (SFD). d-Mannitol and l-leucine were used as the drying adjuvant and aerosol dispersion enhancer, respectively. The DPI formulations were evaluated in vitro in terms of the (1) aerosolization efficiency, (2) aqueous reconstitution, (3) antibiotic release, and (4) antimicrobial activity against respiratory pathogen Pseudomonas aeruginosa. The SFD powders exhibited superior aerosolization efficiency to their SD counterparts in terms of emitted dose (92% versus 66%), fine particle fraction (29% versus 23%), and mass median aerodynamic diameter (3 μm versus 6 μm). The superior aerosolization efficiency of the SFD powders was attributed to their large and porous morphology and higher l-leucine content. While the SFD powders exhibited poorer aqueous reconstitution that might jeopardize their mucus penetrating ability, their antibiotic release profile and antimicrobial activity were not adversely affected.