title: Minimal amounts of dipalmitoylphosphatidylcholine improve aerosol performance of spray-dried temocillin powders for inhalation.
abstract: 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.
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery & Biomaterials, Brussels, Belgium.
authors.forename: Brieuc
authors.initials: B
authors.lastname: Cuvelier
authors.affiliation: Université catholique de Louvain, Institute of Condensed Matter & Nanosciences, Bio & Soft Matter, Louvain-La-Neuve, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Eloy
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery & Biomaterials, Brussels, Belgium.
authors.forename: Cristina
authors.initials: C
authors.lastname: Loira-Pastoriza
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery & Biomaterials, Brussels, Belgium.
authors.forename: Bernard
authors.initials: B
authors.lastname: Ucakar
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery & Biomaterials, Brussels, Belgium.
authors.forename: Abdoul Aziz
authors.initials: AA
authors.lastname: Sanogo
authors.affiliation: Université catholique de Louvain, Institute of Condensed Matter & Nanosciences, Bio & Soft Matter, Louvain-La-Neuve, Belgium.
authors.forename: Christine
authors.initials: C
authors.lastname: Dupont-Gillain
authors.affiliation: Université catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery & Biomaterials, Brussels, Belgium. Electronic address: rita.vanbever@uclouvain.be.
authors.forename: Rita
authors.initials: R
authors.lastname: Vanbever
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000008:administration & dosage* / Q000737:chemistry*; D000280:Administration, Inhalation; D000336:Aerosols / Q000008:administration & dosage* / Q000737:chemistry*; D000818:Animals; D003460:Crystallization; D058995:Dry Powder Inhalers; D005260:Female; D008168:Lung / Q000378:metabolism; D051379:Mice; D010316:Particle Size; D010406:Penicillins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011208:Powders / Q000008:administration & dosage* / Q000737:chemistry*; D012995:Solubility
chemical_list: D000336:Aerosols; D010406:Penicillins; D011208:Powders; C031367:temocillin; D015060:1,2-Dipalmitoylphosphatidylcholine
keywords: Dipalmitoylphosphatidylcholine; Inhalation dry powders; Pulmonary drug delivery; Respiratory infections; Temocillin