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Physicochemical Characterization of Iron Carbohydrate Colloid Drug Products

  • Review Article
  • Theme: Nanotechnology in Complex Drug Products: Learning from the Past, Preparing for the Future
  • Published:
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Abstract

Iron carbohydrate colloid drug products are intravenously administered to patients with chronic kidney disease for the treatment of iron deficiency anemia. Physicochemical characterization of iron colloids is critical to establish pharmaceutical equivalence between an innovator iron colloid product and generic version. The purpose of this review is to summarize literature-reported techniques for physicochemical characterization of iron carbohydrate colloid drug products. The mechanisms, reported testing results, and common technical pitfalls for individual characterization test are discussed. A better understanding of the physicochemical characterization techniques will facilitate generic iron carbohydrate colloid product development, accelerate products to market, and ensure iron carbohydrate colloid product quality.

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Abbreviations

AAS:

Atomic absorption spectroscopy

AFM:

Atomic force microscopy

AUC:

Analytical ultracentrifugation

BDI:

Bleomycin-detectable iron

DLS:

Dynamic light scattering

DPP:

Differential pulse polarography

DSC:

Differential scanning calorimetry

EDX:

Energy-dispersive X-ray

EMR:

Electron magnetic resonance

EPR:

Electron paramagnetic resonance

ESA:

Electrokinetic sonic amplitude

ESR:

Electron spin resonance

EXAFS:

Extended X-ray absorption fine structure

FT-IR:

Fourier transform infrared spectroscopy

GPC:

Gel permeation chromatography

HPLC:

High-performance liquid chromatography

ICP-MS:

Inductively coupled plasma mass spectrometry

MDA:

Malondialdehyde

M aap :

Apparent molecular weight

M n :

Number-average molecular weight

M w :

Weight-average molecular weight

MPS:

Mononuclear phagocyte system

NEXAFS:

Near-edge X-ray absorption fine structure

NMR:

Nuclear magnetic resonance

NPP:

Normal pulse polarography

NTA:

Nitrilotriacetate

NTBI:

Nontransferrin-bound iron

OGD:

Office of Generic Drugs

SLS:

Static light scattering

SQUID:

Superconducting quantum interference device

STEM:

Scanning transmission electron microscope

TBA:

Thiobarbituric acid

TBI:

Transferrin-bound iron

TEM:

Transmission electron microscopy

TEM/NBED:

Transmission electron microscopy/nano beam electron diffraction

TEM/SAED:

Transmission electron microscopy/selected area electron diffraction

TGA:

Thermal gravimetric analysis

USP:

United States Pharmacopeia

UV/Vis:

Ultraviolet-visible spectroscopy

VSM:

Vibrating sample magnetometer

XAS:

X-ray absorption spectroscopy

XANES:

X-ray absorption near-edge structure

XRD:

X-ray diffraction

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  1. Center for Drug Evaluation and Research, US Food and Drug Administration, 10903 New Hampshire Ave, Silver Spring, Maryland, 20993, USA

    Peng Zou, Katherine Tyner, Andre Raw & Sau Lee

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  1. Peng Zou
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Guest Editors: Katherine Tyner, Sau (Larry) Lee, and Marc Wolfgang

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Zou, P., Tyner, K., Raw, A. et al. Physicochemical Characterization of Iron Carbohydrate Colloid Drug Products. AAPS J 19, 1359–1376 (2017). https://doi.org/10.1208/s12248-017-0126-0

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