کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5550603 | 1557296 | 2017 | 9 صفحه PDF | دانلود رایگان |
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 400Â 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 2Â h and an acceleration of 60Â 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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Journal: International Journal of Pharmaceutics - Volume 521, Issues 1â2, 15 April 2017, Pages 337-345