Thermodynamic stability assessment of a colloidal iron drug product: Sodium ferric gluconate
✍ Scribed by Yongsheng Yang; Rakhi B. Shah; Patrick J. Faustino; Andre Raw; Lawrence X. Yu; Mansoor A. Khan
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- English
- Weight
- 235 KB
- Volume
- 99
- Category
- Article
- ISSN
- 0022-3549
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✦ Synopsis
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.