title: Preparation, characterization and pulmonary pharmacokinetics of a new inhalable zanamivir dry powder.
abstract: This work describes a new dry powder for inhalation containing zanamivir, which is less hygroscopic than Relenza®. The powders were prepared via a spray-drying technique using mannitol as the carrier. A 5(3) central composite design was used to optimize the formulations. The final optimized powders, characterized with an angle of repose 37.48°, an aerodynamic diameter of 2.346 μm and in vitro deposition of 58.54%, were obtained by using the predicted variable values. Relenza® absorbed a significant amount of water at 66%, 75% and 85% relative humidity (RH; weight changes of approximately 1.38%, 2.18% and 3.72%, respectively). In contrast, the weight change for the zanamivir dry powder inhalation (DPI) was negligible when the RH was increased to 66%. The in vivo potential for the optimized powders was studied further in rats via the endotracheal administration of an 8.4 mg/kg dose. The bioavailability was 116% relative to Relenza®. Fluorescence imaging monitored the zanamivir dry powder inhalers in rats. The results indicated that the zanamivir DPIs were effectively delivered to the lung. These results indicate that the spray-dried zanamivir DPIs were promising for pulmonary delivery.
authors.affiliation: a Beijing Institute of Pharmacology and Toxicology , Beijing , P.R. China .|b Wuhan Institute of Technology , Wuhan , P.R. China .
authors.forename: Xingshi
authors.initials: X
authors.lastname: Cai
authors.affiliation: a Beijing Institute of Pharmacology and Toxicology , Beijing , P.R. China .
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: a Beijing Institute of Pharmacology and Toxicology , Beijing , P.R. China .|c Department of Pharmacy , Wuhan General Hospital of Guangzhou Military Command , Wuhan , P.R. China , and.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Xie
authors.affiliation: a Beijing Institute of Pharmacology and Toxicology , Beijing , P.R. China .
authors.forename: Fanglin
authors.initials: F
authors.lastname: Yu
authors.affiliation: a Beijing Institute of Pharmacology and Toxicology , Beijing , P.R. China .
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: a Beijing Institute of Pharmacology and Toxicology , Beijing , P.R. China .
authors.forename: Zhenbo
authors.initials: Z
authors.lastname: Yang
authors.affiliation: d Changzhi Medical College , Changzhi , P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: a Beijing Institute of Pharmacology and Toxicology , Beijing , P.R. China .
authors.forename: Xingguo
authors.initials: X
authors.lastname: Mei
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D002626:Chemistry, Pharmaceutical; D058995:Dry Powder Inhalers / Q000379:methods*; D008168:Lung / Q000737:chemistry / Q000187:drug effects*; D008353:Mannitol; D053758:Nanoparticles / Q000737:chemistry*; D061848:Optical Imaging; D051381:Rats; D014961:X-Ray Diffraction; D053243:Zanamivir / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D008353:Mannitol; D053243:Zanamivir
keywords: Central composite design; dry powder inhalation; pulmonary delivery; spray drying; zanamivir