title: In vitro and in vivo evaluation of a dry powder endotracheal insufflator device for use in dose-dependent preclinical studies in mice.
abstract: 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. The emitted fraction varied in vivo compared to the in vitro condition. Fluorescent particle distribution in the lungs was uniform and reached the alveolar spaces, as visualized by fluorescent microscopy. In terms of drug recovery in lung tissue, a minimum administered powder mass (in this case ∼1 mg) was necessary to recover at least 30% of the emitted dose in the lung and to obtain reproducible pulmonary concentrations. To reduce the dose administered in the lung, it was preferable to dilute the active ingredient within the carrier instead of reducing the dry powder mass inserted in the sampling chamber. Dry powder insufflators are devices usable in dose-dependent preclinical trials but have critical parameters to efficiently deliver reproducible doses depending on the type of formulation.
authors.affiliation: Laboratoire de Pharmacie Galénique et de Biopharmacie, Université Libre de Bruxelles, Brussels, Belgium. cduret@ulb.ac.be
authors.forename: Christophe
authors.initials: C
authors.lastname: Duret
authors.forename: Nathalie
authors.initials: N
authors.lastname: Wauthoz
authors.forename: Romain
authors.initials: R
authors.lastname: Merlos
authors.forename: Jonathan
authors.initials: J
authors.lastname: Goole
authors.forename: Calliope
authors.initials: C
authors.lastname: Maris
authors.forename: Isabelle
authors.initials: I
authors.lastname: Roland
authors.forename: Thami
authors.initials: T
authors.lastname: Sebti
authors.forename: Francis
authors.initials: F
authors.lastname: Vanderbist
authors.forename: Karim
authors.initials: K
authors.lastname: Amighi
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D004353:Drug Evaluation, Preclinical / Q000379:methods; D058995:Dry Powder Inhalers; D005079:Excipients / Q000737:chemistry; D017964:Itraconazole / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007834:Lasers; D008168:Lung / Q000378:metabolism*; D008297:Male; D008353:Mannitol / Q000737:chemistry; D051379:Mice; D008813:Mice, Inbred ICR; D008856:Microscopy, Fluorescence; D010316:Particle Size; D010743:Phospholipids / Q000737:chemistry; D015203:Reproducibility of Results; D012542:Scattering, Radiation; D014018:Tissue Distribution
chemical_list: D005079:Excipients; D010743:Phospholipids; D017964:Itraconazole; D008353:Mannitol