Pharmaceutical Research

, Volume 31, Issue 2, pp 449–465 | Cite as

Use of a Fundamental Approach to Spray-Drying Formulation Design to Facilitate the Development of Multi-Component Dry Powder Aerosols for Respiratory Drug Delivery

  • Susan Hoe
  • James W. Ivey
  • Mohammed A. Boraey
  • Abouzar Shamsaddini-Shahrbabak
  • Emadeddin Javaheri
  • Sadaf Matinkhoo
  • Warren H. Finlay
  • Reinhard Vehring
Research Paper



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.


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.


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.


Theoretical models were applied to successfully achieve complex formulations with design challenges a priori. No further iterations to the design process were required.


antimicrobial D-amino acids in silico lung particle formation model spray drying 


Acknowledgments and Disclosures

M. A. Boraey and R. Vehring would like to thank the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Alberta Innovates Technology Futures (AITF) for their financial support.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Susan Hoe
    • 1
  • James W. Ivey
    • 1
  • Mohammed A. Boraey
    • 1
  • Abouzar Shamsaddini-Shahrbabak
    • 1
  • Emadeddin Javaheri
    • 1
  • Sadaf Matinkhoo
    • 1
  • Warren H. Finlay
    • 1
  • Reinhard Vehring
    • 1
  1. 1.Department of Mechanical EngineeringUniversity of AlbertaEdmontonCanada

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