University of Heidelberg, IPMB, Department of Pharmaceutical Technology and Biopharmaceutics, Im Neuenheimer Feld 329, 69120 Heidelberg, Germany.
University of Heidelberg, IPMB, Department of Pharmaceutical Technology and Biopharmaceutics, Im Neuenheimer Feld 329, 69120 Heidelberg, Germany.
Eur J Pharm Biopharm. 2024 Oct;203:114465. doi: 10.1016/j.ejpb.2024.114465. Epub 2024 Aug 22.
In the manufacture of soft gelatin capsules using a rotary-die encapsulation machine, the formation of ribbons at the cooling drums and their subsequent mechanical performance are key attributes for a smooth machinability. In this paper we present the results of a comprehensive investigation of the intricate impact of the cooling drum temperature in the range between 5 and 25 °C on the mechanical and the microstructural properties of a highly concentrated gelatin formulation (40% w/w) typically used in soft capsule manufacture. The study demonstrates that the temperature at the cooling drums strongly affects the gelation kinetics, the gel elasticity and the tensile strength of the ribbons. The temperature correlates linearly with the storage modulus G' under low shear deformation, i.e. the lower the temperature of the gel, the higher the gel elasticity. A reverse linear relationship was found for the temperature-dependent ultimate tensile strength (UTS) of the gelatin ribbons, i.e. a higher drum temperature leads to a higher UTS. This inverse effect of the ageing temperature on G' and UTS can be explained by temperature-induced microstructural differences within the gel network, as indicated by FTIR spectroscopy and Differential Scanning Calorimetry (DSC) measurements. Lower ageing temperatures result in a higher number of triple helical junction zones with fewer and/or weaker hydrogen bonds, which translate into a higher gel elasticity under low shear deformation, but a lower resilience of the ribbons against rupture in tensile testing. At higher temperatures, fewer but longer and/or more thermostable triple helical links in the gel network enhance the stability of the ribbons against tensile stress. In summary, the results clearly reveal that a detailed understanding of the complex relationship between the drum temperature, the gel network structure and the mechanical properties of gelatin ribbons is essential for process optimization.
在使用旋转模压胶囊机制备软明胶胶囊时，冷却鼓上形成的带状物及其随后的机械性能是顺利加工的关键属性。本文介绍了一项综合研究的结果，该研究详细探讨了冷却鼓温度在 5 至 25°C 范围内对高浓度明胶配方（40%w/w）的机械和微观结构性能的复杂影响，该配方通常用于软胶囊制造。研究表明，冷却鼓的温度强烈影响凝胶化动力学、凝胶弹性和带状物的拉伸强度。温度与低剪切变形下的储能模量 G'呈线性相关，即凝胶温度越低，凝胶弹性越高。对于明胶带状物的温度依赖性极限拉伸强度（UTS），发现了相反的线性关系，即鼓的温度越高，UTS 越高。这种老化温度对 G'和 UTS 的反向影响可以通过凝胶网络内的温度诱导微观结构差异来解释，傅里叶变换红外光谱和差示扫描量热法（DSC）测量表明了这一点。较低的老化温度导致更多的三螺旋连接区，氢键数量更少且/或更弱，这在低剪切变形下转化为更高的凝胶弹性，但在拉伸测试中带状物对破裂的弹性更低。在较高温度下，凝胶网络中较短但较长且/或更热稳定的三螺旋键增加了带状物对拉伸应力的稳定性。总之，结果清楚地表明，详细了解鼓温度、凝胶网络结构和明胶带状物机械性能之间的复杂关系对于工艺优化至关重要。
