Dextran or hydroxyethyl starch in spray-freeze-dried trehalose/mannitol microparticles intended as ballistic particulate carriers for proteins.
Dextran or hydroxyethyl starch in spray-freeze-dried trehalose/mannitol microparticles intended as ballistic particulate carriers for proteins.
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喷雾冷冻干燥海藻糖/甘露醇微粒中的葡聚糖或羟乙基淀粉，用作蛋白质的弹道颗粒载体。
DOI：
10.1002/jps.20861
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Geoffrey Lee
中科院分区：
文献类型：
--
作者：
C. Rochelle;Geoffrey Lee
本研究的目的是澄清右旋糖酐10 kDa对用于弹道注射器的喷雾冷冻干燥微粒的性质的影响。已知海藻糖、甘露醇和聚合物的新型载体可使颗粒密度最大化。T '（g）的测量表明，葡聚糖对海藻糖/甘露醇起反增塑作用，但也发生相分离。初步干燥期间产品温度超过T '（g）。因此，可以通过冷冻浓缩物的塑性流动来解释塌陷的颗粒。粉末的DSC显示T（g）为45 ° C，并且在第一次扫描中，出现了由甘露醇重结晶引起的宽吸热熔融峰。过氧化氢酶在其喷雾冷冻干燥（SFD）粉末的再水化时显示出35%的活性损失，这在TM/D（3：3：4）制剂中有所改善，但未达到单独使用海藻糖或甘露醇时观察到的水平。因此，对于最大化颗粒密度至关重要的葡聚糖10 kDa在SFD期间对蛋白质完整性有害，如在65-72 kDa葡聚糖中也发现的。羟乙基淀粉（HES）200 kDa给类似的，有限的稳定作用的蛋白质。制剂中聚合物的比例应低以使蛋白质损伤最小化，同时足够高以得到所需的颗粒形态和密度。
The goal of this study was to clarify the effects of dextran 10 kDa on the properties of spray-freeze-dried microparticles for use with ballistic injectors. A novel carrier of trehalose, mannitol, and the polymer is known to maximize particle density. Measurements of T'(g) showed that the dextran anti-plasticizes the trehalose/mannitol, but also undergoes phase separation. The product temperature exceeded T'(g) during primary drying. The collapsed particles can therefore be explained by plastic flow of the freeze concentrate. DSC of the powder showed T(g) at 45 degrees C and, in the first scan, a wide endothermic melting peak caused by mannitol recrystallization. Catalase showed 35% activity loss on rehydration of its spray freeze-drying (SFD) powder, which was improved in the TM/D (3:3:4) formulation, but not up to that level seen with either trehalose or mannitol alone. The dextran 10 kDa, which is vital to maximize particle density, was therefore detrimental to protein integrity during SFD, as also found with a 65-72 kDa dextran. Hydroxyethyl starch (HES) 200 kDa gave similar, limited stabilizing effects on the protein. The proportion of polymer in the formulation should be low to minimize protein damage, whilst high enough to give required particle morphology and density.