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Issue 4, 2018
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An inert 3D emulsification device for individual precipitation and concentration of amorphous drug nanoparticles

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Abstract

Nanosizing increases the specific surface of drug particles, leading to faster dissolution inside the organism and improving the bioavailability of poorly water-soluble drugs. A novel approach for the preparation of drug nanoparticles in water using chemically inert microfluidic emulsification devices is presented in this paper. A lithographic fabrication sequence was established, allowing fabrication of intersecting and coaxial channels of different depths in glass as is required for 3D flow-focusing. Fenofibrate was used as a model for active pharmaceutical ingredients with very low water solubility in the experiments. It was dissolved in ethyl acetate and emulsified in water, as allowed by the 3D flow-focusing geometry. In the thread formation regime, the drug solution turned into monodisperse droplets of sizes down to below 1 μm. Fast supersaturation occurs individually in each droplet, as the disperse phase solvent progressively diffuses into the surrounding water. Liquid antisolvent precipitation results in highly monodisperse and amorphous nanoparticles of sizes down to 128 nm which can be precisely controlled by the continuous and disperse phase pressure. By comparing optically measured droplet sizes with particle sizes by dynamic light scattering, we could confirm that exactly one particle forms in every droplet. Furthermore, a downstream on-chip concentration allowed withdrawal of major volumes of only the continuous phase fluid which enabled an increase of particle concentration by up to 250 times.

Graphical abstract: An inert 3D emulsification device for individual precipitation and concentration of amorphous drug nanoparticles

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Publication details

The article was received on 08 Dec 2017, accepted on 09 Jan 2018 and first published on 10 Jan 2018


Article type: Paper
DOI: 10.1039/C7LC01313B
Citation: Lab Chip, 2018,18, 627-638
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    An inert 3D emulsification device for individual precipitation and concentration of amorphous drug nanoparticles

    T. Lorenz, S. Bojko, H. Bunjes and A. Dietzel, Lab Chip, 2018, 18, 627
    DOI: 10.1039/C7LC01313B

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