Comparative Physicochemical Characterization between Brand and Generic Intravenous Sodium Ferric Gluconate Complex in Sucrose Injection

Abstract

Oral iron supplementation is commonly used to treat iron anemia. However, some iron anemia associated diseases, such as chronic kidney disease, are only receptive to intravenous (IV) therapies. In the US, there are six reference and one generic colloidal IV iron nanoparticle type formulations approved clinically. The product for which both an innovator and generic are available in the US is sodium ferric gluconate (SFG) (brand - Ferrlecit, generic - Sodium Ferric Gluconate). These formulations function by delivering iron to a protein in the plasma called transferrin. Transferrin subsequently delivers iron to cells to be used for cellular processes. If too much iron is released into the blood plasma, transferrin becomes saturated with iron, and the remaining iron is delivered non-specifically to the cells resulting in toxicity. Compared to conventional small molecule drugs, an extensive functional regulatory standard for generic nanoparticle drug approval has yet to be fully established. Given the complex nature of nanotechnology, the regulatory agencies may require analysis of nanoparticle-based drug products using state-of-the-art tools. It is important to understand which in vitro measures are most appropriate for in vivo predictive during generic drug approval. To attempt to fill these gaps, we have conducted a comprehensive suite of physicochemical measures of brand and generic SFG including total iron content, hydrodynamic diameter, acid solubility, molecular weight distribution, iron core oxidation state, and crystalline order and structure. We have employed a variety of techniques including inductively coupled plasma mass spectrometry, dynamic light scattering, gel permeation chromatography, analytical ultracentrifugation, mössbauer, electron paramagnetic resonance, and x-ray powder diffraction to characterize and compare the physicochemical properties of brand and generic SFG. Our findings will be presented in light of their application to interpret clinical data.