کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2484357 1114308 2016 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Process and Formulation Effects on Protein Structure in Lyophilized Solids Using Mass Spectrometric Methods
ترجمه فارسی عنوان
اثرات فرآیند و فرمولاسیون بر ساختار پروتئین در مواد جامد لیوفیلیز با استفاده از روشهای اسپکترومتری جرمی
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
چکیده انگلیسی
Myoglobin (Mb) was lyophilized in the absence (Mb-A) and presence (Mb-B) of sucrose in a pilot-scale lyophilizer with or without controlled ice nucleation. Cake morphology was characterized using scanning electron microscopy, and changes in protein structure were monitored using solid-state Fourier-transform infrared spectroscopy, solid-state hydrogen-deuterium exchange-mass spectrometry, and solid-state photolytic labeling-mass spectrometry (ssPL-MS). The results showed greater variability in nucleation temperature and irregular cake structure for formulations lyophilized without controlled nucleation. Controlled nucleation resulted in nucleation at ∼(−5°C) and uniform cake structure. Formulations containing sucrose showed better retention of protein structure by all measures than formulations without sucrose. Samples lyophilized with and without controlled nucleation were similar by most measures of protein structure. However, ssPL-MS showed the greatest photoleucine incorporation and more labeled regions for Mb-B lyophilized with controlled nucleation. The data support the use of solid-state hydrogen-deuterium exchange-mass spectrometry and ssPL-MS to study formulation and process-induced conformational changes in lyophilized proteins.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 105, Issue 5, May 2016, Pages 1684-1692
نویسندگان
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