Trnka Hjalte, Rantanen Jukka, Grohganz Holger
Department of Pharmacy, University of Copenhagen , Copenhagen , Denmark.
Pharm Dev Technol. 2015 Jan;20(1):65-73. doi: 10.3109/10837450.2013.871028. Epub 2014 Jan 13.
Freeze-drying in presence of excipients is a common practice to stabilize biomacromolecular formulations. The composition of this formulation is known to affect the quality of the final product.
The aim of this study was to evaluate freeze-drying in well-plates as a high throughput platform for formulation screening of freeze-dried products.
Model formulations consisting of mannitol, sucrose and bovine serum albumin were freeze-dried in brass well plates, plastic well plates and vials. Physical properties investigated were solid form, residual moisture, cake collapse and reconstitution time.
Samples freeze-dried in well-plates had an acceptable visual cake appearance. Solid form analysis by high throughput X-ray powder diffraction indicated comparable polymorphic outcome independent of the container. The expected increase in moisture level due to increasing amount of amorphous matter in the samples was observed in both vials and well plates. Cake collapse was found to be representative in well plates and could be effectively quantified using image analysis. Reconstitution time was also found to be equal in all three platforms. Finally no significant edge effect was found for any of the quality attributes analyzed.
Freeze-drying in well-plates was found to be a suitable and representative high throughput platform for formulation screening.
在赋形剂存在的情况下进行冷冻干燥是稳定生物大分子制剂的常用方法。已知该制剂的组成会影响最终产品的质量。
本研究的目的是评估在微孔板中进行冷冻干燥作为冻干产品制剂筛选的高通量平台。
由甘露醇、蔗糖和牛血清白蛋白组成的模型制剂在黄铜微孔板、塑料微孔板和小瓶中进行冷冻干燥。研究的物理性质包括固体形态、残留水分、饼块塌陷和复溶时间。
在微孔板中冷冻干燥的样品具有可接受的饼块外观。通过高通量X射线粉末衍射进行的固体形态分析表明，无论容器如何，多晶型结果相当。在小瓶和微孔板中均观察到由于样品中无定形物质含量增加导致的水分水平预期升高。发现饼块塌陷在微孔板中具有代表性，并且可以使用图像分析有效地进行量化。在所有三个平台中复溶时间也相等。最后，对于所分析的任何质量属性均未发现明显的边缘效应。
发现微孔板中的冷冻干燥是一种适用于制剂筛选的代表性高通量平台。
