Stabilisation of proteins via mixtures of amino acids during spray drying
Stabilisation of proteins via mixtures of amino acids during spray drying
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DOI：
10.1016/j.ijpharm.2014.01.002
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发表时间：
2014-03-10
影响因子：
5.8
通讯作者：
Scherliess, Regina
中科院分区：
文献类型：
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作者：
Ajmer, Ankur;Scherliess, Regina
生物制剂通常以固体形式配制，以保持稳定性，这通常需要稳定的赋形剂以进行适当的干燥。本研究的目的是筛选氨基酸及其组合在喷雾干燥过程中对蛋白质的稳定作用。过氧化氢酶作为模型蛋白，与氨基酸按1 + 1或1 + 2的比例喷雾干燥。一些氨基酸，如精氨酸、甘氨酸和组氨酸，在喷雾干燥和随后的储存胁迫下，对过氧化氢酶的功能保持良好。精氨酸和甘氨酸以1 + 2的比例与过氧化氢酶进行1 + 1组合，产生了非常好的稳定效果。高温/高湿储存也显示出这种组合的有益效果。为了评估这是否为一般原则，将这些发现转移到具有类似大小和超分子结构的抗原蛋白（血凝素）以及较小的酶（溶菌酶）上。在与氨基酸组合喷雾干燥后，可以表明两种蛋白质在储存后比未保护的蛋白质更稳定。精氨酸和甘氨酸的组合是根据喷雾干燥过程中蛋白质稳定的需要量身定制的，因此可以用于具有优越稳定性特征的生物分子的干粉配方。(C) 2014 Elsevier B.V.版权所有
Biologicals are often formulated as solids in an effort to preserve stability which generally requires stabilising excipients for proper drying. The purpose of this study was to screen amino acids and their combinations for their stabilising effect on proteins during spray drying. Catalase, as model protein, was spray dried in 1 + 1 or 1 + 2 ratios with amino acids. Some amino acids namely arginine, glycine and histidine showed good retention of catalase functionality after spray drying and subsequent storage stress. A 1 + 1 combination of arginine and glycine in a 1 + 2 ratio with catalase resulted in a tremendously good stabilising effect. Storage at high temperature/humidity also showed beneficial effects of this combination. To evaluate whether this was a general principle, these findings were transferred to an antigenic protein of comparable size and supramolecular structure ( haemagglutinin) as well as to a smaller enzyme (lysozyme). Upon spray drying with the combination of amino acids it could be shown that both proteins remain more stable especially after storage compared to the unprotected protein. The combination of arginine and glycine is tailored to the needs of protein stabilisation during spray drying and may hence be utilised in dry powder formulation of biomolecules with superior stability characteristics. (C) 2014 Elsevier B.V. All rights reserved.