کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2484873 | 1114339 | 2012 | 15 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Compatibility, Physical Stability, and Characterization of an IgG4 Monoclonal Antibody After Dilution into Different Intravenous Administration Bags
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Compatibility, Physical Stability, and Characterization of an IgG4 Monoclonal Antibody After Dilution into Different Intravenous Administration Bags Compatibility, Physical Stability, and Characterization of an IgG4 Monoclonal Antibody After Dilution into Different Intravenous Administration Bags](/preview/png/2484873.png)
چکیده انگلیسی
The physical stability of an immunoglobulin G4 monoclonal antibody (mAb) upon dilution into intravenous (i.v.) bags containing 0.9% saline was examined. Soluble aggregates and subvisible particles were observed by sizeâexclusion highâperformance liquid chromatography (SEâHPLC) and light obscuration when formulated with suboptimal levels of polysorbate 20. The formation of soluble aggregates and particulates was further characterized by a combination of SEâHPLC, nanoparticle tracking analysis (NTA), microflowâdigital imaging (MFI), and turbidity measurements. With sufficient PS20 levels, particle formation was minimized, although quantification of submicron sized particles by NTA was not possible because of the interference from PS20. Intravenous bags composed of polyvinyl chloride caused more protein particle formation than polyolefin bags. Differences between bag types were affected by removing headspace and by transferring the saline solution into glass vials. Characterization studies with Fourier transform infrared microscopy and extrinsic fluorescence spectroscopy demonstrated that isolated particles contained nativeâlike secondary structure with partially altered tertiary structure, compared with heatâdenatured and nonstressed controls. Transmission electron microscopy and MFI analysis showed particles had an amorphous morphology of varying sizes. Particles contained some nonânative disulfide bond crosslinks, potentially initiated by low levels of free thiol in the native mAb. The critical role of proper formulation design to stabilize proteins against physical instability during i.v. administration is discussed.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 101, Issue 10, October 2012, Pages 3636-3650
Journal: Journal of Pharmaceutical Sciences - Volume 101, Issue 10, October 2012, Pages 3636-3650
نویسندگان
Ozan S. Kumru, Jun Liu, Junyan A. Ji, Wilson Cheng, Y. John Wang, Tingting Wang, Sangeeta B. Joshi, C. Russell Middaugh, David B. Volkin,