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Int J Pharm. 2014 Apr 10;464(1-2):46-52. doi: 10.1016/j.ijpharm.2014.01.008. Epub 2014 Jan 17.

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

Author information

  • 1Food and Drug Administration, Center for Drug Evaluation and Research Office of Testing and Research, Division of Product Quality Research, 10903 New Hampshire Avenue, Silver Spring, MD 20993, United States.
  • 2Food and Drug Administration, Center for Drug Evaluation and Research Office of Generic Drugs, 7500 Standish Place, Rockville, MD 20855, United States.
  • 3Food and Drug Administration, Center for Drug Evaluation and Research Office of Testing and Research, Division of Product Quality Research, 10903 New Hampshire Avenue, Silver Spring, MD 20993, United States. Electronic address: Patrick.Faustino@fda.hhs.gov.

Abstract

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 0 mV. The complex deformed at low pH and reformed back at the formulation pH. The complex is stable under mild-to-moderate temperature <50°C but aggregates following prolonged exposure to high temperatures >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.

Published by Elsevier B.V.

KEYWORDS:

Chromatography; Colloid; Formulation; Nanoparticles; Stability; Thermodynamic stability

PMID:
24440404
[PubMed - indexed for MEDLINE]
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