Pharmaceutical Research

, Volume 33, Issue 11, pp 2763–2776 | Cite as

Optimization of Spray Drying Conditions for Yield, Particle Size and Biological Activity of Thermally Stable Viral Vectors

  • Daniel A. LeClair
  • Emily D. Cranston
  • Zhou Xing
  • Michael R. Thompson
Research Paper



This work examines the relevance of viral activity in the optimization of spray drying process parameters for the development of thermally stable vaccine powders. In some instances, the actual active pharmaceutical ingredient (API) is not included in the process optimization as it is deemed too costly to use until the final selection of operating conditions, however, that approach is inappropriate for highly labile biopharmaceutics. We investigate the effects of spray drying parameters on i) yield, ii) particle size and iii) viral vector activity of a mannitol/dextran encapsulated recombinant human type 5 adenoviral vector vaccine, to demonstrate the effects and magnitude of each effect on the three responses, and further show that the API must be included earlier in the optimization.


A design of experiments approach was used with response surface methodology (RSM) to optimize parameters including inlet temperature, spray gas flow rate, liquid feed rate and solute concentration in the feed.


In general, good conditions for maintaining viral activity led to reduced yield and fewer particles of the desired size. Within the range of parameters tested, the yield varied from 50 to 90%, the percentage of ideally size particles was 10–50%, and the viral vector titre loss was 0.25–4.0 log loss.


RSM indicates that the most significant spray drying parameters are the inlet temperature and spray gas flow rate. It was not possible to optimize all three output variables with one set of parameters, indicating that there will only be one dominant criteria for processing which in the case of viral vaccines will likely be viral vector activity.


adenovirus optimization particle size process parameters spray dry surface response methodology titre viral vector yield 



Recombinant human type 5 adenoviral vector expressing Escherichia coli β-galactosidase


Active pharmaceutical ingredient


Liquid feed rate


Percentage of particles suitable for dry powder inhalation (1 - 5 μm size)


Relative molecular mass


Peclet number


Response surface methodology


Solute concentration in the liquid feed


Scanning electron microscopy


Spray gas flow rate


Titre log loss


Inlet temperature


Glass transition temperature


Weber number


Powder yield



The authors thank Dr. Pelton for equipment use and Anna Zganiacz and Xueya Feng for cell culture training and general assistance. The authors would also like to thank both the Canadian Centre for Electron Microscopy and the Biointerfaces Institute for use of their facilities. This study is supported by funds from the Canadian Institutes of Health Research and Natural Sciences and Engineering Research Council of Canada.

Supplementary material

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Figure S1 (DOCX 587 kb)
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Figure S2 (DOCX 583 kb)
11095_2016_2003_MOESM3_ESM.docx (585 kb)
Figure S3 (DOCX 584 kb)
11095_2016_2003_MOESM4_ESM.docx (197 kb)
Figure S4 (DOCX 197 kb)


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Daniel A. LeClair
    • 1
  • Emily D. Cranston
    • 1
  • Zhou Xing
    • 2
  • Michael R. Thompson
    • 1
  1. 1.Department of Chemical EngineeringMcMaster UniversityHamiltonCanada
  2. 2.McMaster Immunology Research Centre & Department of Pathology and Molecular MedicineMcMaster UniversityHamiltonCanada

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