Use of leucine to improve aerodynamic properties of ciprofloxacin-loaded maltose microparticles for inhalation

Accepted on: 13 March 2019
Barbara Lamy,a Dolores Remedios Serrano,b,c Peter O’Connell,b William Couet,a,d Sandrine Marchand,a,d Anne Marie Healy,b Frederic Tewes a,*

a INSERM, U1070, UFR de Médecine Pharmacie, Université de Poitiers, 1 rue Georges Bonnet, TSA 51106, 86073 Poitiers Cedex 9, France
b Synthesis and Solid State Pharmaceutical Centre, School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Panoz Institute, Dublin 2, Ireland
c Departamento de Farmacia y Tecnologia Farmaceutica, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza Ramon y Cajal s/n, Madrid, 28040, Spain
d Laboratoire de Toxicologie-Pharmacocinétique, CHU of Poitiers, 2 rue de la Milétrie, 86000 Poitiers, France


Ciprofloxacin (CIP) apparent permeability and absorption rate across the pulmonary epithelium can be controlled by its complexation with copper (II) ion. The aim of the current study was to formulate CIP-Cu-loaded microparticles comprising three main excipients, calcium carbonate, maltose and L-leucine, and to process by spray drying so as to generate particles with suitable aerodynamic properties for pulmonary delivery using a dry powder inhaler. Different maltose:calcium carbonate ratios were used to prepare microparticles, and the role of the excipients on the particles’ physicochemical properties, stability, and aerosolization characteristics were investigated. All the formulations without L-leucine were fully X-ray amorphous. In the presence of L-leucine, diffraction peaks of low intensity were observed, which were attributed to the crystallization of the L-leucine at the particle surfaces. The addition of L-leucine modified the particle morphology and reduced the median geometric and aerodynamic diameters to 3.2 and 3.4 µm, respectively. The fine particle fraction of powder emitted from a Handihaler® device was increased up to 65.4%, predicting high total lung deposition. Stability studies showed that the powder X-ray diffraction pattern did not change over 21 months of storage in desiccated conditions, suggesting a good physical stability of the optimized formulation comprised of CIP-Cu, maltose and L-Leucine.

Number of Downloads: 75