title: Towards a more desirable dry powder inhaler formulation: large spray-dried mannitol microspheres outperform small microspheres.
abstract: OBJECTIVE
  To investigate, for the first time, the performance of a dry powder inhaler (DPI, Aerolizer(®)) in the case of a model drug (i.e. albuterol sulphate) formulated with spray dried mannitol carrier particles with homogeneous shape and solid-state form but different sizes.
  
  
  METHODS
  Spray dried mannitol (SDM) particles were characterized in terms of size, surface area, morphology, water content, solid-state, density and electrostatic charge by a novel approach. DPI formulations composed of SDM and albuterol sulphate (AS) were prepared and evaluated in terms of drug content homogeneity and in vitro aerosolization performance.
  
  
  RESULTS
  All SDM particles generated similar fine particle fractions of AS. Formulations consisting of larger SDM particles demonstrated better drug content homogeneity, reduced amounts of drug loss and reduced oropharyngeal deposition. Comparing different SDM products demonstrated that SDM powders with relatively poorer flowability, wider size distributions and higher charge density generated DPI formulations with poorer drug content homogeneity and deposited higher amount of drug on the inhaler, mouthpiece adaptor and throat. DPI formulation total desirability increased linearly with the mean diameter of SDM.
  
  
  CONCLUSIONS
  Particle shape and solid-state form of mannitol could dominate over carrier size, bulk density, flowability and charge in terms of determining the aerosolization behaviour of AS formulated with mannitol carrier, at least within the experimental protocols applied in the present study.
authors.affiliation: Chemistry and Drug Delivery Group, Medway School of Pharmacy, University of Kent, ME4 4TB, Kent, UK, waseemkaialy@hotmail.co.uk.
authors.forename: Waseem
authors.initials: W
authors.lastname: Kaialy
authors.forename: Tariq
authors.initials: T
authors.lastname: Hussain
authors.forename: Amjad
authors.initials: A
authors.lastname: Alhalaweh
authors.forename: Ali
authors.initials: A
authors.lastname: Nokhodchi
mesh_terms: D000280:Administration, Inhalation; D000420:Albuterol / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry*; D058995:Dry Powder Inhalers / Q000379:methods; D008353:Mannitol / Q000737:chemistry*; D008863:Microspheres; D010316:Particle Size; D016062:Porosity; D011208:Powders / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D011208:Powders; D008353:Mannitol; D000420:Albuterol
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