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48,80 €
ISBN 978-3-8440-6740-8
Softcover
170 pages
48 figures
251 g
21 x 14,8 cm
English
Thesis
June 2019
Thomas Lorenz
Drug Nanoparticle Precipitation by Microfluidic Droplet Generation in Flow-Focusing Devices
Many of today’s discovered active pharmaceutical ingredients (APIs) exhibit poor water-solubility. Orally administered substances that cannot be dissolved inside the organism will leave the body again without any of the desired effects resulting in an erratic performance and low bioavailability inside the organism and the targeted cells. Particle precipitation in microfluidic generated droplets is a promising approach to prepare highly monodisperse nanoparticles. If the particle size is reduced, its specific surface area (SSA). High SSA of API particles result in increased dissolution rates inside the body and therefore in a higher bioavailability and the desired effects.
In this work a microfluidic system was developed for the emulsification of drug loaded droplets in a surrounding aqueous phase and subsequent nanoparticle precipitation. Fenofibrate, a poorly water-soluble API, was selected as model substance. Planar flow-focusing devices made of glass were studied and improved to enable stable generation of micrometer sized oil-in-water droplets in a first step. It was then found that organic solvent had to be used as disperse phase fluid to allow subsequent precipitation of nanoparticles. Wetting of channel walls became an issue due to almost similar contact angles of the continuous and disperse phase. Therefore, 3D flow-focusing devices were fabricated from glass after developing a two-step glass etching process. This allowed stable emulsification of fenofibrate loaded, sub-micron ethyl acetate droplets and subsequent precipitation of fenofibrate nanoparticles. The particles were studied concerning their shape, internal structure, and stability.
Keywords: droplet generation; emulsions; fenofibrate; microfluidics; flow-focusing; nanoparticles; precipitation; poor water-solubility
Schriftenreihe Mikrotechnik
Edited by Prof. Dr. rer.nat. Andreas Dietzel, Braunschweig
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