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. 2019 Jul;140:11-19. doi: 10.1016/j.ejpb.2019.04.010. Epub 2019 Apr 16.
The aim of this study was to investigate the applicability of ATR-FTIR spectroscopy as an analytical tool to monitor the gel formation of highly concentrated gelatin formulations. Spectral changes induced by the coil-helix transition have been studied and related to the elasticity parameter G' obtained by oscillatory rheology in simultaneous measurements. A principal component analysis of the amide I band allowed the evaluation of triple helix formation kinetics. It was found that the key frequencies of the amide I band at 1657 and 1612 cm represent the transition of the gelatin molecules from the random coil to the triple helical conformation in the emerging gel. A direct correlation between the conformation of the gelatin molecules and the gel elasticity was obtained for a commercially available pharmaceutical grade limed bone gelatin in concentrations between 20 and 40% w/w. The same was valid upon addition of small gelatin peptides or a helix inhibitor. No such correlation between triple helix content and G' was found for limed bone gelatins of the same Bloom value but an asymmetric molecular weight distribution with extremely high fractions of high or low molecular weight components. This suggests that early gel elasticity is not solely linked to the triple helix nucleation. Hence, our results indicate that FTIR spectroscopy can be applied to gain a better understanding of the relationship between triple helix content and elastic gel properties of pharmaceutical gelatin capsule shell formulations.
本研究旨在探讨 ATR-FTIR 光谱作为分析工具监测高浓度明胶制剂凝胶形成的适用性。研究了由螺旋-卷曲转变引起的光谱变化，并将其与同时测量得到的振荡流变学中的弹性参数 G'相关联。对酰胺 I 带的主成分分析允许评估三螺旋形成动力学。结果发现，酰胺 I 带的关键频率 1657 和 1612 cm 代表了明胶分子从无规卷曲到新形成的凝胶中的三螺旋构象的转变。对于市售的药用级石灰骨明胶，在 20%至 40%w/w 的浓度范围内，明胶分子的构象与凝胶弹性之间存在直接相关性。在添加小的明胶肽或螺旋抑制剂时，也存在同样的相关性。对于具有相同 Bloom 值但具有极高低分子量组分的不对称分子量分布的石灰骨明胶，则不存在三螺旋含量与 G'之间的这种相关性。这表明早期凝胶弹性不仅与三螺旋成核有关。因此，我们的结果表明，FTIR 光谱可用于更好地理解药物明胶胶囊壳配方中三螺旋含量与弹性凝胶特性之间的关系。
