Carrier-free combination for dry powder inhalation of antibiotics in the treatment of lung infections in cystic fibrosis.

The aim of the study was to develop an efficient combination antibiotic formulation containing tobramycin and clarithromycin as a dry powder for inhalation. A carrier-free formulation of the two drugs was produced by spray-drying and characterised for its aerodynamic behaviour by impaction tests with an NGI and release profiles. The particle size distribution, morphological evaluation and crystallinity state were determined by laser diffraction, scanning electron microscopy and powder X-ray diffraction, respectively.

New co-spray-dried tobramycin nanoparticles-clarithromycin inhaled powder systems for lung infection therapy in cystic fibrosis patients.

The aim of the study was to produce easily dispersible and porous agglomerates of tobramycin nanoparticles surrounded by a matrix composed of amorphous clarithromycin. Nanoparticles of tobramycin with a median particle size of about 400 nm were produced by high-pressure homogenisation. The results from the spray-dried powders showed that the presence of these nanoparticles enhanced powder dispersion during inhalation.

Pharmacokinetic evaluation in mice of amorphous itraconazole-based dry powder formulations for inhalation with high bioavailability and extended lung retention.

Three Itraconazole (ITZ) dry powders for inhalation (DPI) were prepared by spray-drying a mannitol solution in which the ITZ was in suspension (F1) or was in solution without (F2) or with phospholipid (PL) (F3). These powders were endotracheally insufflated in vivo at a single dose of 0.5mg/kg for pharmacokinetic profile (lung and plasma concentration) determination in ICR CD-1 mice.

New inhalation-optimized itraconazole nanoparticle-based dry powders for the treatment of invasive pulmonary aspergillosis.

Purpose: Itraconazole (ITZ) dry powders for inhalation (DPI) composed of nanoparticles (NP) embedded in carrier microparticles were prepared and characterized.

Methods: DPIs were initially produced by reducing the ITZ particle size to the nanometer range using high-pressure homogenization with tocopherol polyethylene 1000 succinate (TPGS, 10% w/w ITZ) as a stabilizer. The optimized nanosuspension and the initial microsuspension were then spray-dried with different proportions of or in the absence of mannitol and/or sodium taurocholate.

New respirable and fast dissolving itraconazole dry powder composition for the treatment of invasive pulmonary aspergillosis.

Purpose: Novel itraconazole (ITZ)-based dry powders for inhalation (DPI) were optimized for aerodynamic and dissolution properties and contained excipients that are acceptable for inhalation.

Methods: The DPI were produced by spray drying solutions. The drug content, crystallinity state, and morphological evaluation of the dry powders were determined by high performance liquid chromatography, powder X-ray diffraction, differential scanning calorimetry, and scanning electron microscopy, respectively.

In vitro and in vivo evaluation of a dry powder endotracheal insufflator device for use in dose-dependent preclinical studies in mice.

The aim of this study was to evaluate the ability of the Penn-Century Dry Powder Insufflator for mice (DP-4M) to reproducibly, uniformly, and deeply deliver dry powders for inhalation in the mouse lung. Itraconazole-based dry powder formulations produced by spray-drying were different in terms of composition (different ratios of drug and mannitol, with or without phospholipids), but relatively similar in terms of particle size and mass median aerodynamic diameter. The ability of the dry powder insufflator to disaggregate each formulation was the same, indicated by the absence of a statistically significant difference between the particle size distribution parameters, as measured by laser scattering.

Solid dispersions of itraconazole for inhalation with enhanced dissolution, solubility and dispersion properties.

The purpose of this study was to produce a dry powder for inhalation (DPI) of a poorly soluble active ingredient (itraconazole: ITZ) that would present an improved dissolution rate and enhanced solubility with good aerosolization properties. Solid dispersions of amorphous ITZ, mannitol and, when applicable, D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) were produced by spray-drying hydro-alcoholic solutions in which all agents were dissolved. These dry formulations were characterized in terms of their aerosol performances and their dissolution, solubility and physical properties.

Formulation and characterization of lipid-coated tobramycin particles for dry powder inhalation.

Purpose: This study was conducted to develop and evaluate the physicochemical and aerodynamic characteristics of lipid-coated dry powder formulations presenting particularly high lung deposition.

Methods: Lipid-coated particles were prepared by spray-drying suspensions with different concentrations of tobramycin and lipids. The solid-state properties of the formulations, including particle size and morphology, were assessed by scanning electron microscopy and laser diffraction.

Pharmacoscintigraphic evaluation of lipid dry powder budesonide formulations for inhalation.

Lung deposition of new formulations of budesonide, using solid lipid microparticles (SLmP) as a pharmaceutically acceptable filler and carrier for inhalation aerosols, and administered from a dry powder inhaler (Cyclohaler), were compared with that from Pulmicort Turbuhaler. Six healthy volunteers took part in a three-way randomized cross-over study, and inhaled a nominal dose of 400 microg budesonide, labelled with 99mTc, on each study day. Lung deposition was determined by gamma scintigraphy and by a pharmacokinetic method.

Preparation and in vitro evaluation of lipidic carriers and fillers for inhalation.

The present study relates to compositions of solid lipidic microparticles (SLmP), composed of biocompatible phospholipids and cholesterol, and their use as carriers or as fillers delivering drugs directly to the lungs via a dry powder inhaler (DPI). SLmP were obtained by spray-drying and were formulated as lipidic matrices entrapping budesonide or as physical blends (drug carrier). They were developed in order to improve the delivery of the active drug by the pulmonary route.