During the continuous crystallization of various solid lipid nanoparticle (LNP) formulations, certain formulations lead to fouling and blocking of small passages in the applied micro heat exchanger. In order to investigate the fouling behavior of different LNP formulations in detail, integral fouling evaluations by pressure drop measurements were performed. Results show more fluctuations compared to particle fouling experiments in macro devices. These variations result from detached agglomerates from compounds formed in micro devices in the inlet header regions, breaking off randomly due to shear stress. This results in downstream microchannel blockage, in the transfer tubings or in subsequent unit operations. During corresponding cleaning experiments different observations compared to macro dimensions were made: Based on significant lower ratios of characteristic dimension of the microchannel to particle or agglomerate diameter, agglomerates remain in the microchannels, preventing smaller particles from being washed off (i.e., capturing effect). Furthermore, low Reynolds numbers, high surface-to-volume ratios, and small characteristic dimensions may result in a total blockage of microchannels.