Thermal Gradient Mid- and Far-Infrared Spectroscopy as Tools for Characterization of Protein Carbohydrate Lyophilizates,Molecular Pharmaceutics

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Thermal Gradient Mid- and Far-Infrared Spectroscopy as Tools for Characterization of Protein Carbohydrate Lyophilizates
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2017-09-15 00:00:00 , DOI: 10.1021/acs.molpharmaceut.7b00568
M. A. Mensink _{1,

2} , J. Šibík _{3,

4} , H. W. Frijlink ₁ , K. van der Voort Maarschalk _{1,

5} , W. L. J. Hinrichs ₁ , J. A. Zeitler ₃

Affiliation

Protein drugs play an important role in modern day medicine. Typically, these proteins are formulated as liquids requiring cold chain processing. To circumvent the cold chain and achieve better storage stability, these proteins can be dried in the presence of carbohydrates. We demonstrate that thermal gradient mid- and far-infrared spectroscopy (FTIR and THz-TDS, respectively) can provide useful information about solid-state protein carbohydrate formulations regarding mobility and intermolecular interactions. A model protein (BSA) was lyophilized in the presence of three carbohydrates with different size and protein stabilizing capacity. A gradual increase in mobility was observed with increasing temperature in formulations containing protein and/or larger carbohydrates (oligo- or polysaccharides), lacking a clear onset of fast mobility as was observed for smaller molecules. Furthermore, both techniques are able to identify the glass transition temperatures (T_g) of the samples. FTIR provides additional information as it can independently monitor changes in protein and carbohydrate bands at the T_g. Lastly, THz-TDS confirms previous findings that protein–carbohydrate interactions decrease with increasing molecular weight of the carbohydrate, which results in decreased protein stabilization.

中文翻译：

热梯度中红外和远红外光谱作为表征蛋白冻干蛋白的工具

蛋白药物在现代医学中起着重要作用。通常，将这些蛋白质配制成需要冷链处理的液体。为了绕过冷链并获得更好的存储稳定性，可以在碳水化合物存在的情况下干燥这些蛋白质。我们证明了热梯度中红外光谱和远红外光谱（分别为FTIR和THz-TDS）可以提供有关固态蛋白质碳水化合物制剂有关迁移率和分子间相互作用的有用信息。在三种具有不同大小和蛋白质稳定能力的碳水化合物的存在下，将模型蛋白质（BSA）冻干。在含有蛋白质和/或较大碳水化合物（寡糖或多糖）的配方中，随着温度的升高，迁移率逐渐增加。缺乏对较小分子的快速迁移的明显发作。此外，两种技术都能够确定玻璃化转变温度（T _g）的样品。FTIR提供了更多信息，因为它可以独立监控T _g处蛋白质和碳水化合物带的变化。最后，THz-TDS证实了先前的发现，即蛋白质与碳水化合物的相互作用随着碳水化合物分子量的增加而降低，从而导致蛋白质稳定性下降。

更新日期：2017-09-15

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