Efficient production of solid dispersions by spray drying solutions of high solid content using a 3-fluid nozzle

Ari Kauppinen, Joep Broekhuis, Niels Grasmeijer, Wouter Tonnis, Jarkko Ketolainen, Henderik W. Frijlink, Wouter L. J. Hinrichs*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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To evaluate the feasibility of producing solid dispersions with 3-fluid nozzle spray drying to improve the dissolution behavior of lipophilic drugs, 60 experiments were performed based on a Design of Experiment. Solid dispersions with mannitol as a hydrophilic matrix and diazepam as a model drug with a drug load of 20 wt-% were produced. The variables of the experiments were the water/organic solvent ratio, liquid feed flow, total solid content, atomizing airflow and type of organic solvent (ethanol or ethyl acetate). The responses measured were dissolution rate, yield, actual drug load, particle size and crystallinity of diazepam and mannitol. Increasing water/organic solvent ratio was found to be the main factor for enhancing the dissolution rate. The total solid content of the solutions to be spray dried did not affect any of the responses, which means that processing solutions of high concentrations is possible. The choice of organic solvent did not affect the responses as well, i.e. both the fully water miscible solvent ethanol and the poorly water miscible solvent ethyl acetate could be used which makes this production method highly versatile.

Original languageEnglish
Pages (from-to)50-58
Number of pages9
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Publication statusPublished - Feb-2018


  • 3-Fluid nozzle
  • Design of experiments
  • Dissolution rate
  • Lipophilic drug
  • Poor water solubility
  • Solid dispersion
  • Spray drying
  • Yield

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