Pharmaceutical characterization and thermodynamic stability assessment of a colloidal iron drug product: Iron sucrose

Molecular weight stability of iron sucrose under accelerated (40°C) and extreme (90°C) stress conditions monitored by gel permeation chromatogram (GPC): 0 day (▪), 1 day (▪), 3 day (▪), and 7 day (▪) exposures. The study objective was to evaluate the thermodynamic stability of iron sucrose complexes as determined by molecular weight (m.w.) changes. The first part of the study focused on the effect of thermal stress, pH, electrolyte or excipient dilution on the stability of a colloidal iron drug product. Part two focused on the physical and chemical evaluation of the colloidal nature of iron sucrose using a series of characterization experiments: ultracentrifugation, dialysis, particle size, zeta potential, and osmotic pressure analysis. A validated Taguchi-optimized high performance gel permeation chromatography method was used for m.w. determinations. Results indicate m.w. of the iron sucrose complex remained unchanged after excipient dilution, ultracentrifugation, dialysis, and electrolyte dilution. Electrolyte dilution studies indicated the lyophilic nature of the iron sucrose colloid with a particle size of 10nm and zeta potential of 0mV. The complex deformed at low pH and reformed back at the formulation pH. The complex is stable under mild-to-moderate temperature 70°C. In conclusion, the resistance of the complex to breakdown by electrolytic conditions, excipient dilution, ultracentrifugation and the reversible complexation after alteration of formulation pH suggest iron sucrose is a lyophilic colloid in nature and lyophilic colloidals are thermodynamically stable.