聚山梨酯酯級(jí)分的表征及其對(duì)蛋白質(zhì)藥物產(chǎn)品穩(wěn)定性的影響。
Molecular Pharmaceutics?(?IF?4.321?)?Pub Date?:?2020-05-22?, DOI:?10.1021/acs.molpharmaceut.0c00093
Anthony Tomlinson,Isidro E Zarraga,Barthélemy Demeule

聚山梨酯（PS）是生物制藥蛋白質(zhì)制劑中常用的表面活性劑。但是，它們易受多種降解途徑的影響，包括化學(xué)水解，氧化和酶促水解。聚山梨酯也是異質(zhì)混合物，并且已經(jīng)觀察到，降解的模式在不同的途徑之間可能截然不同。分離聚山梨酯（PS20和PS80），并對(duì)其餾分的理化性質(zhì)進(jìn)行表征，例如表面張力，膠束大小，臨界膠束濃度（CMC）和單克隆抗體（mAb）的攪拌保護(hù)。本報(bào)告試圖利用這些信息來告知聚山梨酯在生物制藥配方中降解時(shí)這些特性可能會(huì)如何變化。檢查的理化性質(zhì)揭示了PS類型與聚山梨酯的不同化學(xué)成分之間的某些差異。分餾的聚山梨酸酯的理化性質(zhì)差異可能有助于告知使用PS表面活性劑的生物藥物制劑。重要的是，它們表明PS20的亞種比PS80的亞種相差很多。PS20的餾分顯示出非常不同的臨界膠束濃度和對(duì)平衡表面張力的影響。這些差異以及可能的其他未經(jīng)測(cè)試的參數(shù)，導(dǎo)致模型mAb在攪拌應(yīng)力下的保護(hù)作用大不相同。此外，各種PS餾分形成膠束的傾向可能會(huì)影響兩種聚山梨酯的定量測(cè)量，其中一些依賴膠束化，

Characterization of Polysorbate Ester Fractions and Implications in Protein Drug Product Stability.

Polysorbates (PS) are commonly used surfactants in biopharmaceutical protein formulations. However, they are susceptible to a variety of degradation pathways, including chemical hydrolysis, oxidation, and enzymatic hydrolysis. Polysorbates are also heterogeneous mixtures, and it has been observed that the patterns of degradation can be strikingly different between the different pathways. Polysorbates (PS20 and PS80) were fractionated, and the fractions were characterized for their physicochemical properties, such as surface tension, micelle size, critical micelle concentration (CMC), and agitation protection for a monoclonal antibody (mAb). This report seeks to use this information to inform how these properties might change in polysorbates as they degrade in biopharmaceutical formulations. The physicochemical properties examined shed light on some of the differences between PS types and the different chemical components of polysorbates. Differences in physicochemical properties for fractionated polysorbates could help inform biopharmaceutical formulations that use PS surfactants. Importantly, they show that subspecies of PS20 are far more distinct from each other than those of PS80. Fractions of PS20 showed highly different critical micelle concentrations and effects on equilibrium surface tension. These differences, and possibly other untested parameters, led to vastly different protective effects for a model mAb under agitation stress. Additionally, the propensity of various PS fractions to form micelles can impact both polysorbate quantitation measurements, some of which rely on micellization, and the effective solubility of hydrophobic compounds (e.g., fatty acids) in the surfactant solution.

更新日期：2020-07-06