Effect of Arginine on the Aggregation of Protein in Freeze-Dried Formulations Containing Sugars and Polyol: 1—Formulation Development

被引:0
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作者
Ellen Hackl
Joseph Darkwah
Geoff Smith
Irina Ermolina
机构
[1] De Montfort University,Leicester School of Pharmacy, Faculty of Health and Life Sciences
[2] University of Reading,School of Pharmacy
来源
AAPS PharmSciTech | 2018年 / 19卷
关键词
freeze-drying; L-arginine; mannitol; trehalose; sucrose; moisture uptake;
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学科分类号
摘要
l-arginine was introduced into protein-based freeze-dried formulations to study the ability of arginine to reduce/prevent from protein aggregation during manufacturing, storage and reconstitution of lyophilized protein-based pharmaceuticals. As l-arginine is known to be very hygroscopic, additional excipients which could provide a moisture buffering capacity need to be introduced into the formulation. In the first part of our study—excipient formulation development—the screening of a number of sugars/polyols has been done in order to select the best combination of excipients that, in a complex with l-arginine, can (i) produce freeze-dried cakes with elegant appearance, adequate mechanical properties and reconstitution times, and (ii) resist/minimise the moisture sorption. Various freeze-dried cakes containing l-arginine in combination with mannitol, trehalose, lactose and sucrose were produced and analysed by TGA, DSC, texture analysis, moisture sorption, cake shrinkage, TVIM and SEM. The non-linear dependencies of the physicochemical properties of the freeze-dried cakes on the sugar-to-mannitol ratios were found. The best combinations of excipients (l-arginine, mannitol and trehalose) were selected to be used in the second part of this work, in which the impact of each selected formulation will be studied in relation to the aggregation of a protein.
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页码:896 / 911
页数:15
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