کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5550603 1557296 2017 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
High-throughput screening and scale-up of cocrystals using resonant acoustic mixing
ترجمه فارسی عنوان
غربالگری و افزایش سایکستالها با استفاده از مخلوط صوتی رزونانس
کلمات کلیدی
مکانیکمی، کوکریستالها، مخلوط صوتی رزونانس، شیمی سبز،
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی علوم دارویی
چکیده انگلیسی

This paper explores the effectiveness of resonant acoustic mixing RAM for screening and scale up of cocrystals. 16 cocrystal systems were selected as test cases based on previous literature precedent. A 96 well plate set up in conjunction with zirconia beads was used for cocrystal screening using RAM. A success rate of 80% was obtained in the screen for plates containing solvent or solvent plus Zirconia beads. A proof of concept production of hydrated and anhydrous cocrystals of 1:1 Theophylline Citric acid system at a 400 mg scale was demonstrated using solvent and bead assisted RAM. Finally the parameters affecting the scale up of 2:1 Theophylline Oxalic acid cocrystals was explored in a systematic fashion using a Design of Experiments DOE approach. The RAM parameters of acceleration and mixing time were optimized using the DOE approach. A quantitative XRPD method was developed to determine the extent of conversion to the cocrystal when using RAM Mixing time of 2 h and an acceleration of 60 G were determined to be optimal. The optimized parameters were used to demonstrate scale up of 2:1 Theophylline Oxalic acid cocrystals at an 80 gram scale with a net yield of 94%. RAM is thus established as an environmentally friendly mechanochemical technique for both high throughput screening and scaled up production of cocrystals.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Journal of Pharmaceutics - Volume 521, Issues 1–2, 15 April 2017, Pages 337-345
نویسندگان
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