Advanced search
1 file | 856.20 KB

The relevance of shear, sedimentation and diffusion during spin freezing, as potential first step of a continuous freeze-drying process for unit doses

Joris Lammens (UGent) , Séverine Mortier (UGent) , Laurens De Meyer (UGent) , Brecht Vanbillemont (UGent) , Pieter-Jan Van Bockstal (UGent) , Simon Van Herck (UGent) , Jos Corver (UGent) , Ingmar Nopens (UGent) , Valérie Vanhoorne (UGent) , Bruno De Geest (UGent) , et al.
Author
Organization
Abstract
Recently, a continuous freeze-drying process for the production of unit doses was presented and evaluated. In this concept, the freezing step is modified compared to traditional batch freeze-drying, as glass vials filled with a liquid formulation, are rotated around their longitudinal axis while cooled and frozen with a cold, sterile and inert gas (i.e. spin freezing). Finally, a thin frozen product layer spread over the entire vial wall is achieved. The aim of this paper is twofold: firstly, the relation between the rotation velocity and the relative difference between top and bottom of the frozen product layer thickness was determined for different vial types. Secondly, the impact of shear and centrifugal forces generated during spinning was examined, to find out whether they might cause pharmaceutical instability and sedimentation, respectively. Mechanistic and experimental evaluation showed that shear has no effect on proteins. Calculations showed that the sedimentation and diffusion velocity is too low to cause inhomogeneity in the product layer. In addition, Global Sensitivity Analysis (GSA) and Uncertainty Analysis (UA) were performed in order to account for the uncertainty of the used mechanistic model.
Keywords
Freeze-drying, Shear, Sedimentation, Diffusion, Global sensitivity analysis, Uncertainty analysis, GLOBAL SENSITIVITY-ANALYSIS, PROTEIN MOLECULES, INFLUENZA-VIRUS, CONFORMATION, FORMULATION, STABILITY, MODELS, FLOW

Downloads

  • (...).pdf
    • full text
    • |
    • UGent only
    • |
    • PDF
    • |
    • 856.20 KB

Citation

Please use this url to cite or link to this publication:

Chicago
Lammens, Joris, Séverine Mortier, Laurens De Meyer, Brecht Vanbillemont, Pieter-Jan Van Bockstal, Simon Van Herck, Jos Corver, et al. 2018. “The Relevance of Shear, Sedimentation and Diffusion During Spin Freezing, as Potential First Step of a Continuous Freeze-drying Process for Unit Doses.” International Journal of Pharmaceutics 539 (1-2): 1–10.
APA
Lammens, J., Mortier, S., De Meyer, L., Vanbillemont, B., Van Bockstal, P.-J., Van Herck, S., Corver, J., et al. (2018). The relevance of shear, sedimentation and diffusion during spin freezing, as potential first step of a continuous freeze-drying process for unit doses. INTERNATIONAL JOURNAL OF PHARMACEUTICS, 539(1-2), 1–10.
Vancouver
1.
Lammens J, Mortier S, De Meyer L, Vanbillemont B, Van Bockstal P-J, Van Herck S, et al. The relevance of shear, sedimentation and diffusion during spin freezing, as potential first step of a continuous freeze-drying process for unit doses. INTERNATIONAL JOURNAL OF PHARMACEUTICS. 2018;539(1-2):1–10.
MLA
Lammens, Joris, Séverine Mortier, Laurens De Meyer, et al. “The Relevance of Shear, Sedimentation and Diffusion During Spin Freezing, as Potential First Step of a Continuous Freeze-drying Process for Unit Doses.” INTERNATIONAL JOURNAL OF PHARMACEUTICS 539.1-2 (2018): 1–10. Print.
@article{8570102,
  abstract     = {Recently, a continuous freeze-drying process for the production of unit doses was presented and evaluated. In this concept, the freezing step is modified compared to traditional batch freeze-drying, as glass vials filled with a liquid formulation, are rotated around their longitudinal axis while cooled and frozen with a cold, sterile and inert gas (i.e. spin freezing). Finally, a thin frozen product layer spread over the entire vial wall is achieved. The aim of this paper is twofold: firstly, the relation between the rotation velocity and the relative difference between top and bottom of the frozen product layer thickness was determined for different vial types. Secondly, the impact of shear and centrifugal forces generated during spinning was examined, to find out whether they might cause pharmaceutical instability and sedimentation, respectively. Mechanistic and experimental evaluation showed that shear has no effect on proteins. Calculations showed that the sedimentation and diffusion velocity is too low to cause inhomogeneity in the product layer. In addition, Global Sensitivity Analysis (GSA) and Uncertainty Analysis (UA) were performed in order to account for the uncertainty of the used mechanistic model.},
  author       = {Lammens, Joris and Mortier, S{\'e}verine and De Meyer, Laurens and Vanbillemont, Brecht and Van Bockstal, Pieter-Jan and Van Herck, Simon and Corver, Jos and Nopens, Ingmar and Vanhoorne, Val{\'e}rie and De Geest, Bruno and De Beer, Thomas and Vervaet, Chris},
  issn         = {0378-5173},
  journal      = {INTERNATIONAL JOURNAL OF PHARMACEUTICS},
  keyword      = {Freeze-drying,Shear,Sedimentation,Diffusion,Global sensitivity analysis,Uncertainty analysis,GLOBAL SENSITIVITY-ANALYSIS,PROTEIN MOLECULES,INFLUENZA-VIRUS,CONFORMATION,FORMULATION,STABILITY,MODELS,FLOW},
  language     = {eng},
  number       = {1-2},
  pages        = {1--10},
  title        = {The relevance of shear, sedimentation and diffusion during spin freezing, as potential first step of a continuous freeze-drying process for unit doses},
  url          = {http://dx.doi.org/10.1016/j.ijpharm.2018.01.009},
  volume       = {539},
  year         = {2018},
}

Altmetric
View in Altmetric
Web of Science
Times cited: