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A high-throughput multi-microfluidic crystal generator (MMicroCryGen) platform for facile screening of polymorphism and crystal morphology for pharmaceutical compounds†
Lab on a Chip ( IF 6.1 ) Pub Date : 2018-06-14 00:00:00 , DOI: 10.1039/c8lc00301g
E. Simone 1, 2, 3, 4, 5 , J. McVeigh 4, 5, 6, 7 , N. M. Reis 4, 5, 5, 6, 7 , Z. K. Nagy 4, 5, 6, 7, 8
Affiliation  

In this work, a novel multi-microfluidic crystallization platform called MMicroCryGen is presented, offering a facile methodology for generating individual crystals for fast and easy screening of the polymorphism and crystal habit of solid compounds. The MMicroCryGen device is capable of performing 8 × 10 cooling crystallization experiments in parallel using 8 disposable microcapillary film strips, each requiring less than 25 μL of solution. Compared to traditional microfluidic systems, the MMicroCryGen platform does not require complex fluid handling; it can be directly integrated with a 96-well microplate and it can also work in a “dipstick” mode. The produced crystals can be safely and directly observed inside the capillaries by optical and spectroscopic techniques. The platform was validated by performing a number of independent experimental runs for: (1) polymorph and hydrate screening of ortho-aminobenzoic acid, succinic acid and piroxicam; (2) co-crystal form screening of the p-toluenesulfonamide/triphenylphosphine oxide system; (3) studying the effect of o-toluic acid on ortho-aminobenzoic cooling crystallization (effect of structurally related additives). In all three cases, all known solid forms were identified with a single experiment using ∼200 μL of solvent and just a few micrograms of the solid material. The MMicroCryGen is simple to use, inexpensive and it provides increased flexibility compared to traditional crystallization techniques, being an effective new microfluidic solution for solid form screening in pharmaceutical, fine chemicals, food and agrochemical industries.

中文翻译:

高通量多微流体晶体生成器(MMicroCryGen)平台,可轻松筛选药物化合物的多态性和晶体形态

在这项工作中,提出了一种称为MMicroCryGen的新型多微流体结晶平台,它提供了一种简便的方法来生成单个晶体,以便快速,轻松地筛选固体化合物的多态性和晶体习性。MMicroCryGen器件能够使用8个一次性微毛细管薄膜条并行进行8×10冷却结晶实验,每个条带需要少于25μL的溶液。与传统的微流体系统相比,MMicroCryGen平台不需要复杂的流体处理;它可以直接与96孔微孔板集成,也可以在“浸量尺”模式下工作。可以通过光学和光谱技术安全,直接地观察到产生的晶体。氨基苯甲酸,琥珀酸和吡罗昔康;(2)对-甲苯磺酰胺/三苯基氧化膦体系的共晶形式筛选;(3)研究甲苯甲酸对氨基苯甲酸冷却结晶的影响(结构相关添加剂的影响)。在这三种情况下,所有已知的固体形式都可以通过一次实验来确定,该实验使用约200μL溶剂和仅几微克的固体物质。MMicroCryGen使用简便,价格便宜,并且与传统的结晶技术相比,具有更大的灵活性,是一种有效的新型微流体解决方案,可用于制药,精细化工,食品和农业化学工业中的固体形式筛选。
更新日期:2018-06-14
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