Highly protein-loaded melt extrudates produced by small-scale ram and twin-screw extrusion - evaluation of extrusion process design on protein stability by experimental and numerical approaches
Understanding of generation, extent and location of thermomechanical stress in small-scale (< 3 g) ram and twin-screw melt-extrusion is crucial for mechanistic correlations to the stability of protein particles (lysozyme and BSA) in PEG-matrices. The aim of the study was to apply and correlate ex...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | International Journal of Pharmaceutics: X |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590156723000403 |
| _version_ | 1797785508657496064 |
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| author | Katharina Dauer Kevin Kayser Felix Ellwanger Achim Overbeck Arno Kwade Heike P. Karbstein Karl G. Wagner |
| author_facet | Katharina Dauer Kevin Kayser Felix Ellwanger Achim Overbeck Arno Kwade Heike P. Karbstein Karl G. Wagner |
| author_sort | Katharina Dauer |
| collection | DOAJ |
| description | Understanding of generation, extent and location of thermomechanical stress in small-scale (< 3 g) ram and twin-screw melt-extrusion is crucial for mechanistic correlations to the stability of protein particles (lysozyme and BSA) in PEG-matrices. The aim of the study was to apply and correlate experimental and numerical approaches (1D and 3D) for the evaluation of extrusion process design on protein stability. The simulation of thermomechanical stress during extrusion raised the expectation of protein degradation and protein particle grinding during extrusion, especially when TSE was used. This was confirmed by experimental data on protein stability. Ram extrusion had the lowest impact on protein unfolding temperatures, whereas TSE showed significantly reduced unfolding temperatures, especially in combination with kneading elements containing screws. In TSE, the mechanical stress in the screws always exceeded the shear stress in the die, while mechanical stress within ram extrusion was generated in the die, only. As both extruder designs revealed homogeneously distributed protein particles over the cross section of the extrudates for all protein-loads (20–60%), the dispersive power of TSE revealed not to be decisive. Consequently, the ram extruder would be favored for the production of stable protein-loaded extrudates in small scale. |
| first_indexed | 2024-03-13T00:55:03Z |
| format | Article |
| id | doaj.art-49d3b690b008401ab896548ce704099d |
| institution | Directory Open Access Journal |
| issn | 2590-1567 |
| language | English |
| last_indexed | 2024-03-13T00:55:03Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | International Journal of Pharmaceutics: X |
| spelling | doaj.art-49d3b690b008401ab896548ce704099d2023-07-07T04:27:49ZengElsevierInternational Journal of Pharmaceutics: X2590-15672023-12-016100196Highly protein-loaded melt extrudates produced by small-scale ram and twin-screw extrusion - evaluation of extrusion process design on protein stability by experimental and numerical approachesKatharina Dauer0Kevin Kayser1Felix Ellwanger2Achim Overbeck3Arno Kwade4Heike P. Karbstein5Karl G. Wagner6Department of Pharmaceutics, Institute of Pharmacy, University of Bonn, Bonn, GermanyDepartment of Pharmaceutics, Institute of Pharmacy, University of Bonn, Bonn, GermanyInstitute of Process Engineering in Life Sciences, Food Process Engineering, Karlsruhe Institute of Technology, Karlsruhe, GermanyTechnische Universität Braunschweig, Institute for Particle Technology (iPAT) and Center of Pharmaceutical Engineering, Braunschweig, GermanyTechnische Universität Braunschweig, Institute for Particle Technology (iPAT) and Center of Pharmaceutical Engineering, Braunschweig, GermanyInstitute of Process Engineering in Life Sciences, Food Process Engineering, Karlsruhe Institute of Technology, Karlsruhe, GermanyDepartment of Pharmaceutics, Institute of Pharmacy, University of Bonn, Bonn, Germany; Corresponding author.Understanding of generation, extent and location of thermomechanical stress in small-scale (< 3 g) ram and twin-screw melt-extrusion is crucial for mechanistic correlations to the stability of protein particles (lysozyme and BSA) in PEG-matrices. The aim of the study was to apply and correlate experimental and numerical approaches (1D and 3D) for the evaluation of extrusion process design on protein stability. The simulation of thermomechanical stress during extrusion raised the expectation of protein degradation and protein particle grinding during extrusion, especially when TSE was used. This was confirmed by experimental data on protein stability. Ram extrusion had the lowest impact on protein unfolding temperatures, whereas TSE showed significantly reduced unfolding temperatures, especially in combination with kneading elements containing screws. In TSE, the mechanical stress in the screws always exceeded the shear stress in the die, while mechanical stress within ram extrusion was generated in the die, only. As both extruder designs revealed homogeneously distributed protein particles over the cross section of the extrudates for all protein-loads (20–60%), the dispersive power of TSE revealed not to be decisive. Consequently, the ram extruder would be favored for the production of stable protein-loaded extrudates in small scale.http://www.sciencedirect.com/science/article/pii/S2590156723000403Hot-melt extrusionProtein formulationSolid-state stabilityComputational fluid dynamicsNumerical simulation |
| spellingShingle | Katharina Dauer Kevin Kayser Felix Ellwanger Achim Overbeck Arno Kwade Heike P. Karbstein Karl G. Wagner Highly protein-loaded melt extrudates produced by small-scale ram and twin-screw extrusion - evaluation of extrusion process design on protein stability by experimental and numerical approaches International Journal of Pharmaceutics: X Hot-melt extrusion Protein formulation Solid-state stability Computational fluid dynamics Numerical simulation |
| title | Highly protein-loaded melt extrudates produced by small-scale ram and twin-screw extrusion - evaluation of extrusion process design on protein stability by experimental and numerical approaches |
| title_full | Highly protein-loaded melt extrudates produced by small-scale ram and twin-screw extrusion - evaluation of extrusion process design on protein stability by experimental and numerical approaches |
| title_fullStr | Highly protein-loaded melt extrudates produced by small-scale ram and twin-screw extrusion - evaluation of extrusion process design on protein stability by experimental and numerical approaches |
| title_full_unstemmed | Highly protein-loaded melt extrudates produced by small-scale ram and twin-screw extrusion - evaluation of extrusion process design on protein stability by experimental and numerical approaches |
| title_short | Highly protein-loaded melt extrudates produced by small-scale ram and twin-screw extrusion - evaluation of extrusion process design on protein stability by experimental and numerical approaches |
| title_sort | highly protein loaded melt extrudates produced by small scale ram and twin screw extrusion evaluation of extrusion process design on protein stability by experimental and numerical approaches |
| topic | Hot-melt extrusion Protein formulation Solid-state stability Computational fluid dynamics Numerical simulation |
| url | http://www.sciencedirect.com/science/article/pii/S2590156723000403 |
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