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A high-throughput multi-microfluidic crystal generator (MMicroCryGen) platform for facile screening of polymorphism and crystals morphology for pharmaceutical compounds

Abstract

In this work a novel multi-microfluidic crystallization platform called MMicroCryGen is presented, enabling the generation of single crystals and fast and easy screening for polymorphism and crystal habit of solid compounds without any complex fluid handling. The MMicroCryGen device allows performing 8×10 cooling crystallization experiments in parallel using 8 disposable micro-capillary film strips, each containing 10 independent capillaries of 25 μL volume. Compared to traditional microfluidic systems the MMicroCryGen platform does not require complex fluid handling, it can be directly integrated with a 96 wells microplate and it can also work in “dipstick” mode. The produced crystals can be safely and directly observed inside the capillaries via optical and spectroscopic techniques. The platform was validated by performing a number of independent experimental runs aiming: (1) polymorph and hydrate screening for ortho-aminobenzoic acid, succinic acid and piroxicam; (2) co-crystal form screening for the p-Toluenesulfonamide/triphenylphosphine oxide system; (3) a study on the effect of o-toluic acid on ortho-aminobenzoic cooling crystallization (effect of structurally related additives). In the three cases all known solid forms were identified with a single experiment, a total amount of solvent of about 200 μL and only few micrograms of and solid material. The MMicroCryGen presents great simplicity of use, lower cost and greater flexibility compared to traditional crystallization techniques, being an effective new microfluidic solution for solid form screening for pharmaceutical, fine chemicals, food and agrochemical industries.

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Publication details

The article was received on 23 Mar 2018, accepted on 13 Jun 2018 and first published on 14 Jun 2018


Article type: Paper
DOI: 10.1039/C8LC00301G
Citation: Lab Chip, 2018, Accepted Manuscript
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    A high-throughput multi-microfluidic crystal generator (MMicroCryGen) platform for facile screening of polymorphism and crystals morphology for pharmaceutical compounds

    E. Simone, J. McVeigh, N. M. Reis and Z. Nagy, Lab Chip, 2018, Accepted Manuscript , DOI: 10.1039/C8LC00301G

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