Structural characterization of iron oxide/hydroxide nanoparticles in nine different parenteral drugs for the treatment of iron deficiency anaemia by electron diffraction (ED) and X-ray powder diffraction (XRPD)

Drug products containing iron oxide and hydroxide nanoparticles (INPs) are important for the treatment of iron deficiency anaemia. Pharmaceuticals prepared by the complexation of different kinds of INPs and carbohydrates have different physicochemical and biopharmaceutic characteristics. The increasing number of parenteral non-biological complex drugs (NBCD) containing iron requires physicochemical methods for characterization and enabling of cross comparisons. In this context the structure and the level of crystallinity of the iron phases may be connected to the in vitro and in vivo dissolution rates, which etiologically determine the therapeutic and toxic effects. X-ray powder diffraction (XRPD) and electron diffraction (ED) methods were used in order to investigate the nine different parenteral iron formulations Ferumoxytol (Feraheme (R)), sodium ferric gluconate sucrose (Ferrlecit (R)), iron sucrose (Venofer (R)), low molecular weight iron dextran (CosmoFer (R)), low molecular weight iron dextran (Infed (R)), high molecular weight iron dextran (Ironate (R)), high molecular weight iron dextran (Dexferrum (R)), iron carboxymaltose (Ferinject) and iron isomaltoside 1000 (Monofer (R)). The iron phase in CosmoFer (R), Ferinject (R), Monofer (R), Infed (R), Ironate (R) and Dexferrum (R) was identified as Akaganeite/Akaganeite-like (beta-FeOOH), with low amounts of chloride. By combining results of both methods the iron oxide in Feraheme (R) was identified as Magnetite (Fe3O4) with spinel-like structure. Ferrlecit (R) and Venofer (R) were difficult to analyze due to the low degree of crystallinity, but the iron phase seems to fit Lepidocrocite/Lepidocrocite-like (gamma-FeOOH) or an amorphous kind of structure. The structural information on the type of iron oxide or hydroxide together with the particle size allows predicting the stability of the different complexes including their labile iron content. The combination of ED and XRPD methods is a very helpful approach especially for structural analysis of nanoscopic or low crystalline materials. (C) 2013 Elsevier B.V. All rights reserved.