Department of Pharmaceutical Technology and Biopharmacy, University of Groningen , Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.
Janssen Vaccines and Prevention , Archimedesweg 4, 2333 CN Leiden, The Netherlands.
Mol Pharm. 2017 Oct 2;14(10):3550-3557. doi: 10.1021/acs.molpharmaceut.7b00568. Epub 2017 Sep 15.
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) of the samples. FTIR provides additional information as it can independently monitor changes in protein and carbohydrate bands at the T. Lastly, THz-TDS confirms previous findings that protein-carbohydrate interactions decrease with increasing molecular weight of the carbohydrate, which results in decreased protein stabilization.
蛋白质药物在现代医学中发挥着重要作用。通常，这些蛋白质被制成需要冷链处理的液体。为了避免冷链并实现更好的储存稳定性，可以在碳水化合物存在下对这些蛋白质进行干燥。我们证明，热梯度中红外和远红外光谱（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的关于流动性和分子间相互作用的有用信息。模型蛋白质（BSA）在三种具有不同大小和蛋白质稳定能力的碳水化合物存在下冻干。在含有蛋白质和/或较大碳水化合物（寡糖或多糖）的制剂中，随着温度的升高，流动性逐渐增加，而在较小分子中观察到的快速流动性的起始并不明显。此外，这两种技术都能够识别样品的玻璃化转变温度（T）。FTIR 提供了额外的信息，因为它可以独立监测 T 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，即随着碳水化合物分子量的增加，蛋白质-碳水化合物相互作用会降低，从而导致蛋白质稳定性降低。
