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

IF 5.2 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Katharina Dauer , Kevin Kayser , Felix Ellwanger , Achim Overbeck , Arno Kwade , Heike P. Karbstein , Karl G. Wagner
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Abstract

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.

Abstract Image

小规模冲压和双螺杆挤出生产的高蛋白熔体挤出物——用实验和数值方法评估挤出工艺设计对蛋白质稳定性的影响
了解小规模(<3g)冲压和双螺杆熔体挤出中热机械应力的产生、程度和位置对于PEG基质中蛋白质颗粒(溶菌酶和BSA)的稳定性的机制相关性至关重要。本研究的目的是应用实验和数值方法(1D和3D)并将其关联起来,以评估挤压工艺设计对蛋白质稳定性的影响。挤压过程中热机械应力的模拟提高了挤压过程中蛋白质降解和蛋白质颗粒研磨的预期,特别是当使用TSE时。蛋白质稳定性的实验数据证实了这一点。冲压挤压对蛋白质展开温度的影响最小,而TSE显示出显著降低的展开温度,尤其是与含有螺杆的捏合元件结合时。在TSE中,螺钉中的机械应力总是超过模具中的剪切应力,而冲压挤压中的机械力仅在模具中产生。由于两种挤出机设计都显示,对于所有蛋白质负载(20-60%),蛋白质颗粒在挤出物的横截面上均匀分布,TSE的分散能力并不是决定性的。因此,柱塞挤出机将有利于小规模生产稳定的蛋白质负载挤出物。
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来源期刊
International Journal of Pharmaceutics: X
International Journal of Pharmaceutics: X Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
6.60
自引率
0.00%
发文量
32
审稿时长
24 days
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