Wahl Verena, Saurugger Eva, Khinast Johannes, Laggner Peter
Research Center Pharmaceutical Engineering, Graz, Austria; Institute for Process and Particle Engineering, University of Technology, Graz, Austria.
Research Center Pharmaceutical Engineering, Graz, Austria.
Eur J Pharm Biopharm. 2015 Jan;89:374-82. doi: 10.1016/j.ejpb.2014.12.018. Epub 2014 Dec 20.
The nano-structural properties of six different batches of lyophilized fibrinogen at various contents of residual humidity (6-20%) were studied by small- and wide-angle X-ray scattering (SWAXS) and related to the dissolution properties. As structural parameters, the specific surface and relative degree of crystallinity, from SAXS and WAXS, respectively, were used, and correlated to the dissolution rates. BET surface area and electron microscopy were used as ancillary methods. The results show a complex, biphasic behavior: above 9% water content the crystallinity increased, and the specific surface decreased with increasing water contents; at the lowest water contents (6%), however, where the WAXS patterns showed amorphous structure of the fibrinogens, the specific surface and dissolution rates diverged over a wide range of values. Systematic correlations could be established between specific surface and dissolution rates for the water contents below 13%: the dissolution rates were found to decrease with increasing specific surface, most notably in the amorphous form, in contrast to expectations from classical thermodynamics. Protein conformational changes and hydrophobic surface formation upon depletion of water could be possible causes. This is supported by the protective effect of the high-HLB surfactant PS-80, which was found to enlarge the specific surface.
通过小角和广角X射线散射（SWAXS）研究了六种不同批次的冻干纤维蛋白原在不同残余湿度（6%-20%）下的纳米结构特性，并将其与溶解特性相关联。作为结构参数，分别使用了小角X射线散射（SAXS）和广角X射线散射（WAXS）得到的比表面积和相对结晶度，并将其与溶解速率相关联。BET比表面积和电子显微镜用作辅助方法。结果显示出一种复杂的双相行为：含水量超过9%时，结晶度增加，比表面积随含水量增加而减小；然而，在最低含水量（6%）时，WAXS图谱显示纤维蛋白原的无定形结构，比表面积和溶解速率在很宽的值范围内出现差异。对于含水量低于13%的情况，可以在比表面积和溶解速率之间建立系统的相关性：发现溶解速率随比表面积增加而降低，最明显的是在无定形形式中，这与经典热力学的预期相反。水分耗尽时蛋白质构象变化和疏水表面形成可能是原因。高HLB值表面活性剂PS-80的保护作用支持了这一点，发现它会增大比表面积。
