title: Edge activators and a polycationic polymer enhance the formulation of porous voriconazole nanoagglomerate for the use as a dry powder inhaler.
abstract: OBJECTIVE
  Voriconazole has both low aqueous solubility and stability. We hypothesize that designing voriconazole in the form of a nano powder inhaler at a geometric diameter within 1-5 μm will enhance its stability and solubility. Therefore, we prepared nanoagglomerates of voriconazole which will collapse in the lungs to reform the nanoparticles.
  
  
  METHODS
  The nanoparticles were formulated using both stearic acid and sodium deoxycholate as edge activators. Osmogenic polycation polyethyleneimine (PEI) was used to form agglomerates of controllable size.
  
  
  RESULTS
  Voriconazole nanoparticles and agglomerates showed a significant higher cumulative drug release than the pure powder (p < 0.05) with R(2 )=( )0.95. Small-sized particles were formed (353 nm), while their zeta potential was -30.7 mV. The agglomerates were 2.7 μm in size and their zeta potential was -20.9 mV. The formation of porous agglomerates was confirmed using a transmission electron microscope. Cascade impactor was used to evaluate the aerodynamic properties of the nanoparticles and the agglomerates. The aerodynamic characterization of the nanoparticles and the agglomerates resulted in a significant smaller mass median aerodynamic diameter (MMAD) (p < 0.05) and higher fine particle dose (FPD) (p < 0.01), fine particle fraction (FPF) (p < 0.01), and total emitted dose (TED) (p < 0.01) than the pure powder.
  
  
  CONCLUSIONS
  The results suggest that using the combination of edge activators and diluted polycationic polymer solution provides porous voriconazole nanoagglomerates in a respirable range, which is proved successful in enhancing both the deposition and the dissolution of water insoluble-drugs in the lung.
authors.affiliation: a Department of Pharmaceutics and Industrial Pharmacy and.
authors.forename: Heba F
authors.initials: HF
authors.lastname: Salem
authors.affiliation: a Department of Pharmaceutics and Industrial Pharmacy and.
authors.forename: Rasha M
authors.initials: RM
authors.lastname: Kharshoum
authors.affiliation: a Department of Pharmaceutics and Industrial Pharmacy and.
authors.forename: Lekaa F
authors.initials: LF
authors.lastname: Abdel Hakim
authors.affiliation: b Department of Clinical Pharmacy , Faculty of Pharmacy, The University of Beni-Suef , Beni-Suef , Egypt.
authors.forename: Mohamed E
authors.initials: ME
authors.lastname: Abdelrahim
mesh_terms: D002412:Cations / Q000737:chemistry; D045744:Cell Line, Tumor; D004339:Drug Compounding; D065546:Drug Liberation; D058995:Dry Powder Inhalers; D006801:Humans; D008168:Lung / Q000378:metabolism; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D010316:Particle Size; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D016062:Porosity; D012995:Solubility; D013499:Surface Properties; D065819:Voriconazole / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D002412:Cations; D011108:Polymers; D065819:Voriconazole
keywords: Agglomerates; dry powder aerosol; lung deposition; nanoparticles; voriconazole