کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5550113 1557285 2017 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Towards understanding polyol additive effects on the pH shift-induced aggregation of a monoclonal antibody using high throughput screening and quantitative structure-activity modeling
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی علوم دارویی
پیش نمایش صفحه اول مقاله
Towards understanding polyol additive effects on the pH shift-induced aggregation of a monoclonal antibody using high throughput screening and quantitative structure-activity modeling
چکیده انگلیسی

pH shift-induced aggregation is frequently observed in downstream processing of monoclonal antibodies and has been shown to depend on solvent composition. To quantify the stabilizing effect of polyol additives against aggregation, we determined aggregation rate constants in the presence of a set of 14 compounds. Rate constants were then correlated with molecular descriptors in a quantitative structure activity relationship (QSAR) approach. The molecular size, volume, the charge, number of hydrogen acceptors, the stereochemistry and hydrophobicity of the compounds were identified as important descriptors. Generally larger compounds with a balanced surface polarity tend to inhibit aggregation better while hydrophobicity plays an important role at the nucleation phase, with hydrophobic compounds being more potent at inhibiting aggregation.

108

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Journal of Pharmaceutics - Volume 530, Issues 1–2, 15 September 2017, Pages 165-172
نویسندگان
, , , ,