title: Fluticasone and budesonide nanosuspensions for pulmonary delivery: preparation, characterization, and pharmacokinetic studies.
abstract: This manuscript describes the preparation, characterization, and pharmacokinetic studies for fluticasone and budesonide nanosuspensions in pulmonary delivery. A wet-milling method with glass beads was evaluated for formulation preparation. Based on the milling time and glass bead size studies, a 24-h wet-milling process using multisized glass beads was found to be the most efficient method to achieve consistent particle size reduction. It was used to prepare nanosuspensions for characterization and pharmacokinetic studies to evaluate formulation performance. For characterization studies, particle size distribution, crystalline form, potency and homogeneity, and stability during storage were evaluated. Nanosuspensions for both compounds exhibited good physical/chemical properties for pulmonary delivery. The pharmacokinetic studies after the intratracheal administration of nanosuspensions showed deep lung deposition and fast lung absorption, with solubility playing an important role in lung retention and duration of action. Overall, these studies have demonstrated that nanosuspensions can be used for pulmonary drug delivery in preclinical animal studies.
authors: Pharmaceutical Sciences, Pfizer Global Research and Development, St. Louis Laboratories, Pfizer, Inc, St. Louis, Missouri 63017, USA. jerry.z.yang@pfizer.com
authors: Jerry Z
authors: JZ
authors: Yang
authors: Anthony L
authors: AL
authors: Young
authors: Po-Chang
authors: PC
authors: Chiang
authors: Archie
authors: A
authors: Thurston
authors: Denise K
authors: DK
authors: Pretzer
mesh_terms: D000730:Androstadienes / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D019819:Budesonide / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D002853:Chromatography, Liquid; D000068298:Fluticasone; D008168:Lung; D008297:Male; D053758:Nanoparticles; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry; D014961:X-Ray Diffraction
chemical_list: D000730:Androstadienes; D001993:Bronchodilator Agents; D019819:Budesonide; D000068298:Fluticasone