Pharmaceutical characterization and thermodynamic stability assessment of a colloidal iron drug product: iron sucrose.
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.
Food 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.
Rakhi B
RB
Shah
Food 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.
Yongsheng
Y
Yang
Food 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.
Mansoor A
MA
Khan
Food and Drug Administration, Center for Drug Evaluation and Research Office of Generic Drugs, 7500 Standish Place, Rockville, MD 20855, United States.
Andre
A
Raw
Food and Drug Administration, Center for Drug Evaluation and Research Office of Generic Drugs, 7500 Standish Place, Rockville, MD 20855, United States.
Lawrence X
LX
Yu
Food 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.
Patrick J
PJ
Faustino
D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003102:Colloids; D004355:Drug Stability; D005290:Ferric Compounds / Q000737:chemistry* / Q000592:standards*; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid / Q000737:chemistry* / Q000592:standards*; D013816:Thermodynamics
D003102:Colloids; D005290:Ferric Compounds; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid
Chromatography; Colloid; Formulation; Nanoparticles; Stability; Thermodynamic stability