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Nanoparticles as an application platform for active ingredients offer the advantage of efficient absorption and rapid dissolution in the organism, even in cases of poor water solubility. Active substances can either be presented directly as nanoparticles or can be integrated in a colloidal carrier system (e.g., lipid nanoparticles). For bottom-up nanoparticle production minimizing particle contamination, precipitation processes provide an adequate approach. Microfluidic systems ensure a precise control of mixing for the precipitation, which enables a tunable particle size definition. In this work, a gas/liquid Taylor flow micromixer made of chemically inert glass is presented, in which the organic phases are injected through a symmetric inlet structure. The 3D structuring of the glass was performed by femtosecond laser ablation. Rough microchannel walls are typically obtained by laser ablation but were smoothed by a subsequent annealing process resulting in lower hydrophilicity and even rounder channel cross-sections. Only with such smooth channel walls can a substantial reduction of fouling be obtained, allowing for stable operation over longer periods. The ultrafast mixing of the solutions could be adjusted by simply changing the gas volume flow rate. Narrow particle size distributions are obtained for smaller gas bubbles with a low backflow and when the rate of liquid volume flow has a small influence on particle precipitation. Therefore, nanoparticles with adjustable sizes of down to 70 nm could be reliably produced in continuous mode. Particle size distributions could be narrowed to a polydispersity value of 0.12.

Poorly soluble drugs can be incorporated in lipid carrier nanoparticles to achieve sufficient bioavailability and open up diverse routes of administration. Preparation by antisolvent precipitation in microfluidic systems enables excellent...

Microfluidic processes are of interest for the production of pharmaceutical nanoparticles due to the uniform characteristics attainable by such devices. However, precipitation processes in microfluidic systems incur a high risk of fouling, which compromises their reliability for continuous operation. A robust ultrasound‐assisted process is established for the precipitation of lipid nanoparticles in a microfluidic mixer. The results indicate that nanoparticles can be produced over several hours without clogging. An analysis of the products reveals a small number of micron‐sized particles, but these did not disturb the process. Thus, in‐process ultrasonication is effective at improving the reliability of microfluidic precipitation and preventing buildup of precipitates in the channels.