Pilot-scale co-precipitation synthesis of a novel active ingredient made of ultrasmall iron (oxyhydr)oxide nanoparticles for the treatment of hyperphosphatemia.

Due to its simplicity, co-precipitation is the most commonly used method for producing iron (oxyhydr)oxide nanoparticles. However, it is reported to be sensitive to changes in process parameters, which complicates scale-up and is why only volumes up to 1.2 L have been described in the literature. This study aims to demonstrate the scale-up of a co-precipitation synthesis to 100 L using the example of a new phosphate-binding active ingredient based on iron (oxyhydr)oxide. The synthesis was shown to be very robust to changes in synthesis parameters and stirrer geometries. The in vitro phosphate-binding efficacy and the yield were maintained in all five scales tested. Only the content of the components in the nanoparticles varied slightly. However, Mössbauer spectroscopy, dynamic light scattering (DLS), and attenuated total reflection Fourier transform infrared spectroscopy (FT-IR) revealed no evidence of structural changes, but a reduction in the size of the iron (oxyhydr)oxide cores and the total core-shell nanoparticle sizes. Overall, this study has successfully demonstrated that ultrasmall iron (oxyhydr)oxide nanoparticles can be produced on a pilot scale by co-precipitation with a yield of >40 g L-1.

Interaction and mechanisms in the phosphate-binding of iron(oxyhydr)oxide core-shell nanoparticles.

HYPOTHESIS: The high binding affinity of iron(oxyhydr)oxides for phosphate has recently been used in medicine to treat hyperphosphatemia, an abnormally elevated phosphate concentration in the blood. For iron(oxyhydr)oxide nanoparticles, the composition of the organic shell has a more significant influence on their interaction with phosphate than is often assumed. This study shows different mechanisms in phosphate binding, using the example of two similar new phosphate-binding agents. EXPERIMENTS: We characterized the phosphate-binding behavior of two iron(oxyhydr)oxide-based nanomaterials with similar composition and particle properties and investigated their binding mechanisms by spectroscopic methods. FINDINGS: For the often prescribed Velphoro, we demonstrated a phosphate binding capacity of>210 mg/g. A similar active ingredient named C-PAM binds over 573 mg/g. Spectroscopic measurements highlighted differences in the binding mechanism. While Velphoro binds phosphate via surface complexation independent of pH and adsorbent concentration, C-PAM shows a strong concentration dependence. At low concentrations, phosphate is bound via complexation reactions. The iron(oxyhydr)oxide structure was dissolved at higher phosphate concentrations and formed various iron phosphate species. The substances behave differently upon interaction with phosphate, although being very similar in composition and crystal structure. Thus, we demonstrated a crucial influence of the ligands in the shell on the binding mechanism.