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

Administration of antibiotics by inhalation can greatly improve drug targeting to the site of respiratory infections. In addition, dry powder inhalers are convenient and can reduce daily treatment burden. However, the powder mass that can be inhaled each time is limited and the formulation of highly-dosed antibiotics for inhalation requires the incorporation of a limited amount of excipient. The purposes of this study were i) to demonstrate the interest of pulmonary temocillin delivery to reach high temocillin concentrations locally in the lungs and ii) to prepare a spray-dried temocillin powder for inhalation using a minimal amount of generally recognized as safe excipients. Pulmonary delivery of temocillin 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 opens interesting perspectives for this excipient in the formulation of antibiotic dry powders for inhalation.