Multi-Solvent Microdroplet Evaporation: Modeling and Measurement of Spray-Drying Kinetics with Inhalable Pharmaceutics

Mani Ordoubadi, Florence K.A. Gregson, Omar Melhem, David Barona, Rachael E.H. Miles, Dexter D’Sa, Sandra Gracin, David Lechuga-Ballesteros, Jonathan P. Reid, Warren H. Finlay, Reinhard Vehring*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

14 Citations (Scopus)
49 Downloads (Pure)


Purpose: Evaporation and particle formation from multi-solvent microdroplets containing solid excipients pertaining to spray-drying of therapeutic agents intended for lung delivery were studied. Various water and ethanol co-solvent systems containing a variety of actives and excipients (beclomethasone, budesonide, leucine, and trehalose) were considered. Methods: Numerical methods were used to predict the droplet evaporation rates and internal solute transfers, and their results verified and compared with results from two separate experimental setups. In particular, an electrodynamic balance was used to measure the evaporation rates of multicomponent droplets and a monodisperse droplet chain setup collected dried microparticles for further analytical investigations and ultramicroscopy. Results: The numerical results are used to explain the different particle morphologies dried from solutions at different co-solvent compositions. The obtained numerical data clearly show that the two parameters controlling the general morphology of a dried particle, namely the Péclet number and the degree of saturation, can change with time in a multi-solvent droplet. This fact complicates product development for such systems. However, this additional complexity vanishes at what we define as the iso-compositional point, which occurs when the solvent ratios and other composition-dependent properties of the droplet remain constant during evaporation, similar to the azeotrope of such systems during distillation. Conclusions: Numerical and experimental analysis of multi-solvent systems indicate that spray-drying near the iso-compositional ratio simplifies the design and process development of such systems.

Original languageEnglish
Article number100
Number of pages17
JournalPharmaceutical Research
Early online date14 May 2019
Publication statusE-pub ahead of print - 14 May 2019


  • co-solvents
  • inhaled therapeutics
  • microparticles
  • multi-solvent spray-drying
  • particle engineering


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