Continuous preparation of itraconazole nanoparticles using droplet-based microreactor

The nano-sized drug is an alternative strategy for enhancing the dissolution rate of pharmaceutical ingredients with poor solubility. Microfluidic technology has been widely applied for the preparation of nanoparticles because of its controllability. Combining the above two concerns, this study proposed an anti-solvent precipitation method to obtain itraconazole (ITZ) nanoparticles using a continuous flow droplet-based microreactor. In addition to the experimental study of the generation of different shapes of droplets, the influencing factors of nanoparticle preparation such as the flow rate ratio of the dispersed phase to the continuous phase, the residence time, the drug initial concentration and the stabilizer were further analyzed. The advantages of the droplets system were fully demonstrated in comparison with the conventional laminar flow system in the form of the T microfluidic device. The results showed that smaller nanoparticles of itraconazole with narrower size distribution were prepared in droplets and addressed that the particle agglomeration and growth would be restrained in droplets under the increased residence time, higher initial concentration or amphiphilic stabilizers.