The influence of lysozyme on mannitol polymorphism in freeze-dried and spray-dried formulations depends on the selection of the drying process
The influence of lysozyme on mannitol polymorphism in freeze-dried and spray-dried formulations depends on the selection of the drying process
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DOI：
10.1016/j.ijpharm.2013.03.003
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发表时间：
2013-04-15
影响因子：
5.8
通讯作者：
Yang, Mingshi
中科院分区：
文献类型：
--
作者：
Grohganz, Holger;Lee, Yan-Ying;Yang, Mingshi
冷冻干燥和喷雾干燥通常是用于生物制药制剂的干燥技术。干燥时不同固体形式的形成通常取决于赋形剂选择和工艺参数之间的复杂相互作用。本研究的目的是研究所选择的干燥方法对固态形式的影响。将20 mg/mL的甘露醇-溶菌酶溶液（其中溶菌酶的量在总固体含量的2.5%和50%（w/w）之间变化）分别冷冻干燥和喷雾干燥。通过近红外光谱结合多变量分析对所得甘露醇的固态进行分析，并进一步用X射线粉末衍射验证结果。可以看出，随着冻干制剂中蛋白质浓度的增加，甘露醇多晶型的流行率从β-甘露醇转移到δ-甘露醇。在喷雾干燥制剂中，蛋白质浓度的增加导致从β-甘露醇转变为α-甘露醇。冷冻干燥工艺的最终干燥温度向喷雾干燥工艺的温度升高不会导致显著变化。因此可以得出结论，是干燥过程本身而不是温度导致观察到的固态变化。(C)2013年爱思唯尔B。V.保留所有权利。
Freeze-drying and spray-drying are often applied drying techniques for biopharmaceutical formulations. The formation of different solid forms upon drying is often dependent on the complex interplay between excipient selection and process parameters. The purpose of this study was to investigate the influence of the chosen drying method on the solid state form. Mannitol-lysozyme solutions of 20 mg/mL, with the amount of lysozyme varying between 2.5% and 50% (w/w) of total solid content, were freeze-dried and spray-dried, respectively. The resulting solid state of mannitol was analysed by near-infrared spectroscopy in combination with multivariate analysis and further, results were verified with X-ray powder diffraction. It was seen that the prevalence of the mannitol polymorphic form shifted from beta-mannitol to delta-mannitol with increasing protein concentration in freeze-dried formulations. In spray-dried formulations an increase in protein concentration resulted in a shift from beta-mannitol to alpha-mannitol. An increase in final drying temperature of the freeze-drying process towards the temperature of the spray-drying process did not lead to significant changes. It can thus be concluded that it is the drying process in itself, rather than the temperature, that leads to the observed solid state changes. (C) 2013 Elsevier B. V. All rights reserved.