Effects of Excipient Interactions on the State of the Freeze-Concentrate and Protein Stability
Effects of Excipient Interactions on the State of the Freeze-Concentrate and Protein Stability
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DOI：
10.1007/s11095-016-2078-y
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发表时间：
2017-02-01
影响因子：
3.7
通讯作者：
Aksan, Alptekin
中科院分区：
文献类型：
--
作者：
Jena, Sampreeti;Horn, Jacqueline;Aksan, Alptekin
目的冻干制剂中辅料的物理状态直接影响有效药物成分(API)的稳定性。海藻糖和甘露醇在冷冻溶液中的结晶已被证明是组成的函数。然而，有关原料药和其他辅料的浓度对甘露醇和海藻糖在冷冻溶液中结晶度影响的详细研究尚未见报道。方法采用差示扫描量热法、X射线衍射法和傅里叶变换红外光谱对甘露醇和海藻糖在冷冻溶液中的结晶度进行表征。用傅里叶变换红外光谱和圆二色谱对BSA的二级结构进行了表征。BSA延缓和降低了甘露醇和海藻糖的结晶程度。加入D2O(=5%w/w)和低浓度的聚山梨酯20(
Purpose The physical state of excipients in freeze-dried formulations directly affects the stability of the active pharmaceutical ingredient (API). Crystallization of trehalose and mannitol in frozen solutions has been shown to be a function of composition. However, to date a detailed study of the effect of concentrations of the API and other excipients on the crystallinity of mannitol and trehalose in frozen solutions has not been reported.Methods The crystallinity of mannitol and trehalose in frozen solutions was characterized by Differential Scanning Calorimetry, X-ray diffractometry, and FTIR spectroscopy. The secondary structure of BSA was probed by FTIR, and Circular Dichroism spectroscopy in frozen and thawed solutions, respectively.Results Trehalose crystallization was accompanied by unfolding of BSA. BSA delayed and reduced the extent of mannitol and trehalose crystallization. Similar effects were observed upon adding D2O (>= 5% w/w) and low concentrations of polysorbate 20 (