title: Use of a fundamental approach to spray-drying formulation design to facilitate the development of multi-component dry powder aerosols for respiratory drug delivery.
abstract: OBJECTIVE
  A fundamental approach incorporating current theoretical models into aerosol formulation design potentially reduces experimental work for complex formulations. A D-amino acid mixture containing D-Leucine (D-Leu), D-Methionine, D-Tryptophan, and D-Tyrosine was selected as a model formulation for this approach.
  
  
  METHODS
  Formulation design targets were set, with the aim of producing a highly dispersible D-amino acid aerosol. Particle formation theory and a spray dryer process model were applied with boundary conditions to the design targets, resulting in a priori predictions of particle morphology and necessary spray dryer process parameters. Two formulations containing 60% w/w trehalose, 30% w/w D-Leu, and 10% w/w remaining D-amino acids were manufactured.
  
  
  RESULTS
  The design targets were met. The formulations had rugose and hollow particles, caused by deformation of a crystalline D-Leu shell while trehalose remained amorphous, as predicted by particle formation theory. D-Leu acts as a dispersibility enhancer, ensuring that both formulations: 1) delivered over 40% of the loaded dose into the in vitro lung region, and 2) achieved desired values of lung airway surface liquid concentrations based on lung deposition simulations.
  
  
  CONCLUSIONS
  Theoretical models were applied to successfully achieve complex formulations with design challenges a priori. No further iterations to the design process were required.
authors: Department of Mechanical Engineering, University of Alberta, Edmonton, Alberta, Canada, T6G 2G8.
authors: Susan
authors: S
authors: Hoe
authors: James W
authors: JW
authors: Ivey
authors: Mohammed A
authors: MA
authors: Boraey
authors: Abouzar
authors: A
authors: Shamsaddini-Shahrbabak
authors: Emadeddin
authors: E
authors: Javaheri
authors: Sadaf
authors: S
authors: Matinkhoo
authors: Warren H
authors: WH
authors: Finlay
authors: Reinhard
authors: R
authors: Vehring
mesh_terms: D000336:Aerosols / Q000737:chemistry*; D000596:Amino Acids / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods; D058995:Dry Powder Inhalers / Q000379:methods; D005079:Excipients / Q000737:chemistry; D008168:Lung / Q000378:metabolism*; D011208:Powders / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods; D014199:Trehalose / Q000737:chemistry
chemical_list: D000336:Aerosols; D000596:Amino Acids; D005079:Excipients; D011208:Powders; D014199:Trehalose
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