Core size determination and structural characterization of intravenous iron complexes by cryogenic transmission electron microscopy

Wu, Yong; Petrochenko, Peter; Chen, Lynn; Wong, Sook Yee; Absar, Mohammad; Choi, Stephanie; Zheng, Jiwen

doi:10.1016/j.ijpharm.2016.03.029

Cited by 36 publications

(20 citation statements)

References 41 publications

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“…As shown in Figure 2 A,C, the dark particles in cryo-TEM images indicate the iron cores with high atomic number that absorb or scatter electrons. Both Ferrlecit and generic SFG consist of dispersed spherical nano-sized iron colloids which have an average size of approximately 2 nm with a narrow size distribution in the native state ( Figure 2 B,D), which is consistent with the reported value [ 13 , 14 ].…”

Section: Resultssupporting

confidence: 90%

“…Both cryo-TEM and AFM analyses measured the iron core size of Ferrlecit and generic SFG. In order to investigate the size distribution and morphology of the iron hydroxide core, the cryo-TEM protocol similar to the previously reported method [ 14 ] was performed. As shown in Figure 2 A,C, the dark particles in cryo-TEM images indicate the iron cores with high atomic number that absorb or scatter electrons.…”

Section: Resultsmentioning

confidence: 99%

“…In order to investigate the size distribution and morphology of the iron hydroxide core, the cryo-TEM protocol, similar to the previously reported method [ 14 ], was performed using a Jeol 1400 TEM/STEM (scanning TEM) operated at 120 kV and viewed under the minimum dose system mode. A 2 mL aliquot of SFG complex products was first placed on a glow-discharged (EMS (electron microscopy science) 150T S) copper grid (Quantifoil R 2/1, 200 mesh) hang in a Leica EM GP grid plunge freezer (Leica Microsystem Inc., Buffalo Grove, IL, USA).…”

Section: Methodsmentioning

confidence: 99%

“…For example, molecular weight distribution of SFG polymers is commonly determined by size exclusion chromatography (e.g., gel permeation chromatography (GPC) [ 10 ]) and also explored with asymmetric field-flow fractionation (AFFF) [ 12 ]. The size distribution and zeta potential of SFG nanoparticles can be measured by a dynamic light scattering (DLS) particle sizing and zeta potential analyzer [ 10 ], and the iron core size can be measured by atomic force microscopy (AFM) [ 13 ] and transmission electron microscopy (TEM) [ 14 ]. More advanced analytical tools such as sedimentation velocity analytical ultracentrifugation (SV-AUC) [ 15 ] have been applied to determine the hydrodynamic radius distribution of nanoparticles.…”

Section: Introductionmentioning

confidence: 99%

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Comparative Evaluation of U.S. Brand and Generic Intravenous Sodium Ferric Gluconate Complex in Sucrose Injection: Physicochemical Characterization

et al. 2018

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The objective of this study was to evaluate physicochemical equivalence between brand (i.e., Ferrlecit) and generic sodium ferric gluconate (SFG) in sucrose injection by conducting a series of comparative in vitro characterizations using advanced analytical techniques. The elemental iron and carbon content, thermal properties, viscosity, particle size, zeta potential, sedimentation coefficient, and molecular weight were determined. There was no noticeable difference between brand and generic SFG in sucrose injection for the above physical parameters evaluated, except for the sedimentation coefficient determined by sedimentation velocity analytical ultracentrifugation (SV-AUC) and molecular weight by asymmetric field flow fractionation-multi-angle light scattering (AFFF-MALS). In addition, brand and generic SFG complex products showed comparable molecular weight distributions when determined by gel permeation chromatography (GPC). The observed minor differences between brand and generic SFG, such as sedimentation coefficient, do not impact their biological activities in separate studies of in vitro cellular uptake and rat biodistribution. Coupled with the ongoing clinical study comparing the labile iron level in healthy volunteers, the FDA-funded post-market studies intended to illustrate comprehensive surveillance efforts ensuring safety and efficacy profiles of generic SFG complex in sucrose injection, and also to shed new light on the approval standards on generic parenteral iron colloidal products.

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Section: Resultssupporting

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Comparative Evaluation of U.S. Brand and Generic Intravenous Sodium Ferric Gluconate Complex in Sucrose Injection: Physicochemical Characterization

et al. 2018

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“…This NDA was approved in 1975. A second drug product, INFeD (iron dextran injection) containing ∼15-nm-sized particles, was approved in 1974 for the treatment of anaemia 14,15 .…”

Section: Submission Trendsmentioning

confidence: 99%

The evolving landscape of drug products containing nanomaterials in the United States

et al. 2017

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The Center for Drug Evaluation and Research (CDER) within the US Food and Drug Administration (FDA) is tracking the use of nanotechnology in drug products by building and interrogating a technical profile of products containing nanomaterials submitted to CDER. In this Analysis, data from more than 350 products show an increase in the submissions of drug products containing nanomaterials over the last two decades. Of these, 65% are investigational new drugs, 17% are new drug applications and 18% are abbreviated new drug applications, with the largest class of products being liposomal formulations intended for cancer treatments. Approximately 80% of products have average particle sizes of 300 nm or lower. This analysis identifies several trends in the development of drug products containing nanomaterials, including the relative rate of approvals of these products, and provides a comprehensive overview on the landscape of nanotechnology application in medicine.

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Innovation for Generic Drugs: Science and Research Under the Generic Drug User Fee Amendments of 2012

Lionberger¹

2019

Clin Pharma and Therapeutics

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Regulatory science is science and research intended to improve decision making in a regulatory framework. Improvements in decision making can be in both accuracy (making better decisions) and in efficiency (making faster decisions). Science and research supported by the Generic Drug User Fee Amendments of 2012 (GDUFA) have focused on two innovative methodologies that work together to enable new approaches to development and review of generic drugs: quantitative models and advanced in vitro product characterization. Quantitative models faithfully represent current scientific understanding. They are tools pharmaceutical scientists and clinical pharmacologists use for making better and faster product development decisions. Advances in the in vitro product comparisons provide the measurements of product differences that are the critical input into the models. This paper outlines four areas where science and research funded by GDUFA support synergistic use of models and characterization at critical decision points during generic drug product development and review.

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Core size determination and structural characterization of intravenous iron complexes by cryogenic transmission electron microscopy

Cited by 36 publications

References 41 publications

Comparative Evaluation of U.S. Brand and Generic Intravenous Sodium Ferric Gluconate Complex in Sucrose Injection: Physicochemical Characterization

Comparative Evaluation of U.S. Brand and Generic Intravenous Sodium Ferric Gluconate Complex in Sucrose Injection: Physicochemical Characterization

The evolving landscape of drug products containing nanomaterials in the United States

Innovation for Generic Drugs: Science and Research Under the Generic Drug User Fee Amendments of 2012

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