Protein drugs present specific challenges to the maintenance of long-term stability, which can be accomplished by altering parameters of obtention, purification, molecule structure and formulation. As we believe, commercial formulations are undervalued; therefore, this review focuses on screening, categorising and discussing all formulations of protein drugs approved and not withdrawn by regulatory agencies from United States, Canada and Europe until mid-2018. Peptides (<50 amino acids) were not included to allow a more precise evaluation of choices for larger molecules. We extracted data from the DrugBank database, cross-checked it with the FDA purple book and supplemented it with patient information leaflets and papers. We further classified and discussed the entries according to protein function, drug delivery, route of administration and types of excipient (freeze-dried forms). In addition, alternative choices of excipients were discussed. Experimental work included here relates to targeting strategies with verified pharmacokinetics or in vivo effectiveness to identify physiologically relevant options. Although no single rule can be set for efficient protein formulation, our data help to better understand and optimise the choice for excipients and pharmaceutical dosage forms. For more information, see the Supplemental Data.

中文翻译：

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蛋白质药物递送：目前的剂型概况和配方策略。

蛋白质药物对维持长期稳定性提出了特定的挑战，这可以通过改变获得、纯化、分子结构和配方的参数来实现。我们认为，商业配方被低估了；因此，本次审查的重点是筛选、分类和讨论美国、加拿大和欧洲监管机构在 2018 年中期之前批准但未撤回的所有蛋白质药物制剂。不包括肽（<50 个氨基酸）以允许更精确地评​​估较大分子的选择。我们从 DrugBank 数据库中提取数据，与 FDA 紫皮书进行交叉核对，并补充患者信息传单和论文。我们根据蛋白质功能、药物递送、给药途径和赋形剂类型（冻干形式）。此外，还讨论了辅料的替代选择。这里包括的实验工作涉及具有经验证的药代动力学或体内有效性的靶向策略，以确定生理相关的选择。尽管不能为有效的蛋白质制剂设定单一规则，但我们的数据有助于更好地理解和优化赋形剂和药物剂型的选择。有关更多信息，请参阅补充数据。我们的数据有助于更好地理解和优化赋形剂和药物剂型的选择。有关更多信息，请参阅补充数据。我们的数据有助于更好地理解和优化赋形剂和药物剂型的选择。有关更多信息，请参阅补充数据。