Thermodynamic stability assessment of a colloidal iron drug product: sodium ferric gluconate.

A high performance gel permeation chromatography (HP-GPC) method was developed, validated and used to determine the molecular weight (MW) of sodium ferric gluconate following various stress conditions. The intra-day accuracy (90-103%), intra-day precision (1.5-2.7%), inter-day accuracy (91-105%), inter-day precision (1.3-3.2%) were within acceptable range stated in FDA guidance. The MW of sodium ferric gluconate remained unchanged after: (1) autoclaving (121 degrees C), (2) moderate thermal stress (30 days at 50 degrees C or 7 days at 70 and 90 degrees C), (3) excipient dilution, (4) basic buffer dilution (pH of 8 and 9), (5) ultracentrifugation, (6) dialysis, and (7) electrolyte dilution. However sodium ferric gluconate showed signs of instability at higher temperatures (>90 degrees C) after 30 days and at pH of 10-11. Sodium ferric gluconate was found to be a lypophilic colloidal solution with an average particle size of 10 nm and a zeta potential of -13 mV. The colloid osmotic pressure was 3.5 mmHg and remained unchanged after moderate thermal stress. Additionally, in-house drug products with similar MW to sodium ferric gluconate were produced by three different synthetic procedures, suggesting that this colloidal iron drug product might be thermodynamically stable.