کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2486062 | 1114374 | 2010 | 14 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Inhibition of AgitationâInduced Aggregation of an IgGâAntibody by HydroxypropylâβâCyclodextrin
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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: Inhibition of AgitationâInduced Aggregation of an IgGâAntibody by HydroxypropylâβâCyclodextrin Inhibition of AgitationâInduced Aggregation of an IgGâAntibody by HydroxypropylâβâCyclodextrin](/preview/png/2486062.png)
چکیده انگلیسی
In order to provide an alternative to nonionic surfactants as excipients for protein formulations, cyclodextrinâderivatives (CDs) were examined for their potential to inhibit agitationâinduced aggregation of an IgG in aqueous solution. Loss of monomeric protein and protein aggregation were monitored throughout the agitation experiments by size exclusion chromatography. Hydroxypropylâβâcyclodextrin (HPβCD) completely suppressed IgGâaggregation at a remarkably low concentration (2.5âmM) and in contrast to other CDs it also did not negatively affect IgGâstability during storage in nonagitated solution. Further agitation experiments demonstrated the superiority of HPβCD to other common excipients in protein formulation, such as sugars and sugar alcohols or polysorbate 80 in low concentrations. Spectroscopic (fluorescence spectroscopy and Fourier transform infrared spectroscopy), thermodynamic (microcalorimetry), and physical investigations (surface tension measurements) were carried out to elucidate the mechanism of stabilization of the IgG. In contrast to other studies with HPβCD, protein stabilization could not be attributed to direct interaction between hydrophobic amino acids on the IgG and this excipient. Competition with the protein for the air-water interface appears to be the dominating mechanism of stabilization. © 2009 WileyâLiss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1193-1206, 2010
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 99, Issue 3, March 2010, Pages 1193-1206
Journal: Journal of Pharmaceutical Sciences - Volume 99, Issue 3, March 2010, Pages 1193-1206
نویسندگان
Tim Serno, John F. Carpenter, Theodore W. Randolph, Gerhard Winter,