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首页> 外文期刊>European journal of pharmaceutical sciences >Overcoming challenges in co-formulation of proteins with contradicting stability profiles - EPO plus G-CSF
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Overcoming challenges in co-formulation of proteins with contradicting stability profiles - EPO plus G-CSF

机译：克服蛋白质共同制定的挑战，稳定性型材 - epo加g-csf

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摘要

The co-formulation of drugs is widely used for small molecules, e.g. fixed-dose-combinations of synergistic medicines in the treatment of infections, diabetes or neurodegenerative diseases. For protein drugs, only a few studies have been published to elucidate the challenges of stabilizing two proteins in one formulation. Here, we show a systematic study with the model proteins EPO and G-CSF, which differ significantly in their physicochemical properties. We apply several analytical methods to investigate the stability of the co-formulated proteins in the liquid and solid state. Forced degradation studies at elevated temperature indicate poor stability of the liquid co-formulations. Therefore, we use lyophilization as a stabilization strategy. Finally, we adopt an elegant approach, in which the proteins are lyophilized at pH 4.0 and reconstituted with buffer at pH 7.0 to obtain high monomer recovery and to preserve the protein structure of both EPO and G-CSF. After reconstitution, both proteins in co-formulation remain stable for the timespan until eventual application in patients. With this case study, we demonstrate how to overcome some challenges during the co-formulation of therapeutic proteins.
机译：药物共同制剂广泛用于小分子，例如小分子。在治疗感染，糖尿病或神经变性疾病中的协同药物的固定剂量组合。对于蛋白质药物，仅公布了一些研究以阐明在一种配方中稳定两种蛋白质的挑战。在这里，我们展示了与模型蛋白质EPO和G-CSF的系统研究，其在其物理化学性质中显着差异。我们应用几种分析方法来研究液体和固态中共配制蛋白的稳定性。升高温度下的强制降解研究表明液体共同制剂的稳定性差。因此，我们使用冻干作为稳定战略。最后，我们采用优雅的方法，其中蛋白质在pH4.0下冻干，并在pH7.0处重构缓冲液，得到高单体回收并保留ePO和G-CSF的蛋白质结构。重构后，共配制中的两种蛋白质对母程保持稳定，直到患者最终应用。通过这种情况，我们展示了如何在治疗蛋白共同制定期间克服一些挑战。

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