Pharmaceutical Research

, 36:43 | Cite as

Particle Surface Roughness Improves Colloidal Stability of Pressurized Pharmaceutical Suspensions

  • Hui Wang
  • David S. Nobes
  • Reinhard VehringEmail author
Research Paper



The effects of particle size and particle surface roughness on the colloidal stability of pressurized pharmaceutical suspensions were investigated using monodisperse spray-dried particles.


The colloidal stability of multiple suspensions in the propellant HFA227ea was characterized using a shadowgraphic imaging technique and quantitatively compared using an instability index. Model suspensions of monodisperse spray-dried trehalose particles of narrow distributions (GSD < 1.2) and different sizes (MMAD = 5.98 μm, 10.1 μm, 15.5 μm) were measured first to study the dependence of colloidal stability on particle size. Particles with different surface rugosity were then designed by adding different fractions of trileucine, a shell former, and their suspension stability measured to further study the effects of surface roughness on the colloidal stability of pressurized suspensions.


The colloidal stability significantly improved (p < 0.001) from the suspension with 15.5 μm-particles to the suspension with 5.98 μm-particles as quantified by the decreased instability index from 0.63 ± 0.04 to 0.07 ± 0.01, demonstrating a strongly size-dependent colloidal stability. No significant improvement of suspension stability (p > 0.1) was observed at low trileucine fraction at 0.4 % where particles remained relatively smooth until the surface rugosity of the particles was improved by the higher trileucine fractions at 1.0 % and 5.0 %, which was indicated by the substantially decreased instability index from 0.27 ± 0.02 for the suspensions with trehalose model particles to 0.18 ± 0.01 (p < 0.01) and 0.03 ± 0.01 (p < 0.002) respectively.


Surface modification of particles by adding shell formers like trileucine to the feed solutions of spray drying was demonstrated to be a promising method of improving the colloidal stability of pharmaceutical suspensions in pressurized metered dose inhalers.

Key words

monodisperse spray drying particle formation shadowgraphic imaging surface roughness suspension stability 


Acknowledgments and Disclosures

The authors acknowledge financial support from the Natural Sciences and Engineering Research Council (NSERC) of Canada, the Alberta Ingenuity Fund and the Canadian Foundation for Innovation (CFI). Hui Wang gratefully acknowledges the scholarship support of Alberta Innovates and Alberta Advanced Education.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Mechanical Engineering, 10-269 Donadeo Innovation Centre for EngineeringUniversity of AlbertaEdmontonCanada

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