کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8514073 1556503 2017 72 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Visualization of Protonation/Deprotonation of Active Pharmaceutical Ingredient in Solid State by Vapor Phase Amine-Selective Alkyne Tagging and Raman Imaging
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
پیش نمایش صفحه اول مقاله
Visualization of Protonation/Deprotonation of Active Pharmaceutical Ingredient in Solid State by Vapor Phase Amine-Selective Alkyne Tagging and Raman Imaging
چکیده انگلیسی
Here, we report a simple and direct method to visualize the protonation/deprotonation of an amine active pharmaceutical ingredient (API) in the solid state using a solid-vapor reaction with propargyl bromide and Raman imaging for the assessment of the API during the manufacturing process of solid formulations. An alkyne tagging occurred on the free form of solid haloperidol by the vapor phase reaction, and a distinct Raman signal of alkyne was detected. Alkyne signal monitoring by Raman imaging enabled us to visualize the distribution of the free-form haloperidol in a solid formulation. On the other hand, haloperidol hydrochloride did not react with propargyl bromide in the solid-vapor reaction, and the alkyne signal was not observed. Using the difference in reactivity, the protonation/deprotonation of the amine API in the solid state could be visualized. As an example of application, we tried to visually assess the protonation/deprotonation state when the free-form haloperidol was ground with acids using the solid-vapor reaction and Raman imaging and found that haloperidol was partially protonated when ground with 2 equivalents of hydrogen chloride. Furthermore, we demonstrated the relationship between the degree of protonation and the amount of water added as a medium for grinding haloperidol with succinic acid.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 106, Issue 7, July 2017, Pages 1778-1785
نویسندگان
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