Minimal amounts of dipalmitoylphosphatidylcholine improve aerosol performance of spray-dried temocillin powders for inhalation

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• 作者：Brieuc Cuvelier^a ; Pierre Eloy^b ; Cristina Loira-Pastoriza^a ; Bernard Ucakar^a ; Abdoul Aziz Sanogo^a ; Christine Dupont-Gillain^b ; Rita Vanbever^a ; ^{rita.vanbever@uclouvain.be" class="auth_mail" title="E-mail the corresponding author}
• 关键词：BAL ; bronchoalveolar lavage ; d ; primary geometric particle diameter ; daer ; primary aerodynamic diameter of the particles ; DPI ; dry powder inhaler ; DPPC ; dipalmitoylphosphatidylcholine ; ED ; emitted dose ; FPF ; fine particle fraction ; GRAS ; generally recognized as safe ; HBSS ; Hank&rsquo ; s balanced salt solution ; HPLC ; high performance liquid chromatography ; MMAD ; mass median aerodynamic diameter ; MSLI ; Multi-Stage Liquid Impinger ; PBS ; phosphate buffer saline ; 蟻 ; powder density ; XPS ; X-ray photoele
• 刊名：International Journal of Pharmaceutics
• 出版年：2015
• 出版时间：30 November 2015
• 年：2015
• 卷：495
• 期：2
• 页码：981-990
• 全文大小：1637 K

文摘

Administration of antibiotics by inhalation can greatly improve drug targeting to the site of respiratory infections. In addition, dry powder inhalers are particularly convenient for the patients. The purposes of this study were to demonstrate the interest of pulmonary temocillin delivery to reach high temocillin concentrations locally in the lungs as well as to prepare a spray-dried temocillin powder for inhalation using a minimal amount of generally recognized as safe excipients. Intratracheal instillation of a temocillin solution allowed to reach higher and more sustained drug concentrations in the lungs than intravenous injection in mice, although a 10-fold lower temocillin dose was delivered intratracheally than systemically. A spray-dried powder of pure temocillin presented a fine particle fraction of 9% of the dose loaded in the inhaler. However, the incorporation of 0.5% to 20% of dipalmitoylphosphatidylcholine (DPPC) in the powder increased the fine particle fraction 4- to 5-fold. X-ray photoelectron spectroscopy and X-ray diffraction revealed that DPPC concentrated at the particle surface with its aliphatic chains laterally packed. The minimal amount of DPPC needed to improve the aerosol performance of temocillin supports the use of this excipient in the formulation of cohesive antibiotic powders for inhalation.