کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2485585 | 1114360 | 2011 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Degradation of Polysorbates 20 and 80: Studies on Thermal Autoxidation and Hydrolysis
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
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چکیده انگلیسی
The purpose of this work was to study the mechanistic pathways of degradation of polysorbates (PS) 20 and PS80 in parenteral formulations. The fate of PS in typical protein formulations was monitored and analyzed by a variety of methods, including 1H NMR, high-performance liquid chromatography/evaporative light scattering detection, and ultraviolet-visible spectroscopy. Oxidative degradation of PS in neat raw material was studied using thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and headspace gas chromatography-mass spectrometry. TGA-DSC studies revealed that autoxidation via a radical mechanism is dominated by statistical random scission in PS20 and PS80. Thermal initiation of radical formation occurs at the polyoxyethylene (POE) as well as the olefin sites. In PS80, radical initiation at the olefinic site precedes initiation at the POE site, leading to modified degradation profile. Corresponding to these results, in aqueous formulations, a surge peroxide content was detected in PS20-containing samples and in higher concentrations in those containing PS80. Hydrolysis in aqueous formulations, as followed by 1H NMR, was found to have a half-life of 5 months at 40°C. On the basis of the obtained results, PSs degrade mainly via autoxidation and also via hydrolysis at higher temperatures. Further studies are required to investigate on potential effects of degradation on surface activity and protein stability in PS-containing formulations.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 100, Issue 2, February 2011, Pages 721-731
Journal: Journal of Pharmaceutical Sciences - Volume 100, Issue 2, February 2011, Pages 721-731
نویسندگان
Ravuri S.K. Kishore, Astrid Pappenberger, Isabelle Bauer Dauphin, Alfred Ross, Beatrice Buergi, Andreas Staempfli, Hanns-Christian Mahler,