title: A Design of Experiment approach to predict product and process parameters for a spray dried influenza vaccine.
abstract: Spray dried vaccine formulations might be an alternative to traditional lyophilized vaccines. Compared to lyophilization, spray drying is a fast and cheap process extensively used for drying biologicals. The current study provides an approach that utilizes Design of Experiments for spray drying process to stabilize whole inactivated influenza virus (WIV) vaccine. The approach included systematically screening and optimizing the spray drying process variables, determining the desired process parameters and predicting product quality parameters. The process parameters inlet air temperature, nozzle gas flow rate and feed flow rate and their effect on WIV vaccine powder characteristics such as particle size, residual moisture content (RMC) and powder yield were investigated. Vaccine powders with a broad range of physical characteristics (RMC 1.2-4.9%, particle size 2.4-8.5μm and powder yield 42-82%) were obtained. WIV showed no significant loss in antigenicity as revealed by hemagglutination test. Furthermore, descriptive models generated by DoE software could be used to determine and select (set) spray drying process parameter. This was used to generate a dried WIV powder with predefined (predicted) characteristics. Moreover, the spray dried vaccine powders retained their antigenic stability even after storage for 3 months at 60°C. The approach used here enabled the generation of a thermostable, antigenic WIV vaccine powder with desired physical characteristics that could be potentially used for pulmonary administration.
authors: Intravacc (Institute for Translational Vaccinology), Antonie van Leeuwenhoeklaan 9, 3720 AL Bilthoven, The Netherlands; University of Groningen, Department of Pharmaceutical Technology and Biopharmacy, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors: Gaurav
authors: G
authors: Kanojia
authors: Intravacc (Institute for Translational Vaccinology), Antonie van Leeuwenhoeklaan 9, 3720 AL Bilthoven, The Netherlands.
authors: Geert-Jan
authors: GJ
authors: Willems
authors: University of Groningen, Department of Pharmaceutical Technology and Biopharmacy, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors: Henderik W
authors: HW
authors: Frijlink
authors: Intravacc (Institute for Translational Vaccinology), Antonie van Leeuwenhoeklaan 9, 3720 AL Bilthoven, The Netherlands; Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
authors: Gideon F A
authors: GF
authors: Kersten
authors: Intravacc (Institute for Translational Vaccinology), Antonie van Leeuwenhoeklaan 9, 3720 AL Bilthoven, The Netherlands. Electronic address: peter.soema@intravacc.nl.
authors: Peter C
authors: PC
authors: Soema
authors: Intravacc (Institute for Translational Vaccinology), Antonie van Leeuwenhoeklaan 9, 3720 AL Bilthoven, The Netherlands.
authors: Jean-Pierre
authors: JP
authors: Amorij
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods*; D005544:Forecasting; D009980:Influenza A virus; D007252:Influenza Vaccines / Q000138:chemical synthesis*; D011420:Propiolactone / Q000138:chemical synthesis*; D015164:Vaccines, Inactivated / Q000138:chemical synthesis
chemical_list: D007252:Influenza Vaccines; D015164:Vaccines, Inactivated; D011420:Propiolactone
keywords: Nozzle gas flow rate; Process optimization; Process parameters; Quality by design; Spray drying