title: Thermodynamic stability assessment of a colloidal iron drug product: sodium ferric gluconate.
abstract: 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.
authors.affiliation: Division of Product Quality Research, Food and Drug Administration, Center for Drug Evaluation and Research, 10903 New Hampshire Avenue, Silver Spring, Maryland 20993.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Yang
authors.forename: Rakhi B
authors.initials: RB
authors.lastname: Shah
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Faustino
authors.forename: Andre
authors.initials: A
authors.lastname: Raw
authors.forename: Lawrence X
authors.initials: LX
authors.lastname: Yu
authors.forename: Mansoor A
authors.initials: MA
authors.lastname: Khan
mesh_terms: D002138:Calibration; D002626:Chemistry, Pharmaceutical; D002850:Chromatography, Gel; D003102:Colloids; D004355:Drug Stability; D005290:Ferric Compounds / Q000737:chemistry* / Q000592:standards; D006863:Hydrogen-Ion Concentration; D015394:Molecular Structure; D008970:Molecular Weight; D011786:Quality Control; D012015:Reference Standards; D013816:Thermodynamics
chemical_list: D003102:Colloids; D005290:Ferric Compounds; C035552:ferric gluconate