title: Systematic aging of degradable nanosuspension ameliorates vibrating-mesh nebulizer performance.
abstract: BACKGROUND
  The process of vibrating-mesh nebulization is affected by sample physicochemical properties. Exemplary, electrolyte supplementation of diverse formulations facilitated the delivery of adequate aerosols for deep lung deposition.
  
  
  OBJECTIVE
  This study addressed the impact of storage conditions of poly(lactide-co-glycolide) nanosuspension on aerosol properties when nebulized by the eFlow®rapid.
  
  
  METHODS
  First, purified nanosuspensions were supplemented with electrolytes (i.e. sodium chloride, lactic and glycolic acid). Second, the degradable nanoparticles (NP) were incubated at different temperatures (i.e. 4, 22 and 36 °C) for up to two weeks. The effect of formulation supplementation and storage on aerosol characteristics was studied by laser diffraction and correlated with the sample conductivity.
  
  
  CONCLUSIONS
  Nebulization of purified nanosuspensions resulted in droplet diameters of >7.0 µm. However, electrolyte supplementation and storage, which led to an increase in sample conductivity (>10-20 µS/cm), were capable of providing smaller droplet diameters during vibrating-mesh nebulization (≤5.0 µm). No relevant change of NP properties (i.e. size, morphology, remaining mass and molecular weight of the employed polymer) was observed when incubated at 22 °C for two weeks.
  
  
  CONCLUSIONS
  Sample aging is an alternative to electrolyte supplementation in order to ameliorate the aerosol characteristics of degradable NP formulations when nebulized by vibrating-mesh technology.
authors.affiliation: a Department of Internal Medicine , Medical Clinic II, Justus-Liebig-Universität , Giessen , Germany.
authors.forename: Alexandra C
authors.initials: AC
authors.lastname: Dalla-Bona
authors.affiliation: a Department of Internal Medicine , Medical Clinic II, Justus-Liebig-Universität , Giessen , Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmehl
authors.affiliation: a Department of Internal Medicine , Medical Clinic II, Justus-Liebig-Universität , Giessen , Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Gessler
authors.affiliation: a Department of Internal Medicine , Medical Clinic II, Justus-Liebig-Universität , Giessen , Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Seeger
authors.affiliation: a Department of Internal Medicine , Medical Clinic II, Justus-Liebig-Universität , Giessen , Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Beck-Broichsitter
mesh_terms: D000336:Aerosols / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D004356:Drug Storage; D004573:Electrolytes / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D011098:Polyglactin 910 / Q000737:chemistry*; D013535:Suspensions / Q000737:chemistry; D013678:Technology, Pharmaceutical; D013696:Temperature
chemical_list: D000336:Aerosols; D004337:Drug Carriers; D004573:Electrolytes; D013535:Suspensions; D011098:Polyglactin 910
keywords: Aerosol; hydrolytic degradation; nanoparticles; poly(lactide-co-glycolide); pulmonary drug delivery; vibrating-mesh nebulizer