title: Specific surface, crystallinity, and dissolution of lyophilized fibrinogen. A study by combined small- and wide-angle X-ray scattering (SWAXS).
abstract: 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.
authors.affiliation: Research Center Pharmaceutical Engineering, Graz, Austria; Institute for Process and Particle Engineering, University of Technology, Graz, Austria.
authors.forename: Verena
authors.initials: V
authors.lastname: Wahl
authors.affiliation: Research Center Pharmaceutical Engineering, Graz, Austria.
authors.forename: Eva
authors.initials: E
authors.lastname: Saurugger
authors.affiliation: Research Center Pharmaceutical Engineering, Graz, Austria; Institute for Process and Particle Engineering, University of Technology, Graz, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Khinast
authors.affiliation: Research Center Pharmaceutical Engineering, Graz, Austria; Bruker AXS, Graz, Austria. Electronic address: peter.laggner@bruker.at.
authors.forename: Peter
authors.initials: P
authors.lastname: Laggner
mesh_terms: D003460:Crystallization / Q000379:methods; D005340:Fibrinogen / Q000737:chemistry*; D005612:Freeze Drying / Q000379:methods; D006813:Humidity; D049329:Nanostructures / Q000737:chemistry*; D011487:Protein Conformation; D053838:Scattering, Small Angle; D012995:Solubility; D013816:Thermodynamics; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction / Q000379:methods; D014965:X-Rays
chemical_list: D014867:Water; D005340:Fibrinogen
keywords: Amorphous; Crystalline; Dissolution; Fibrinogen; Protein; Residual water; SAXS; Specific surface; WAXS; X-ray