Microfluidic synthesis of amorphous cefuroxime axetil nanoparticles with size-dependent and enhanced dissolution rate

Abstract: In this work, size-controllable nanoparticles of amorphous cefuroxime axetil (CFA), a poorly water-soluble drug, have been prepared in a Y-junction microchannel reactor (YMCR) by nanoprecipitation for enhancing dissolution rate of CFA. The effects of the operation parameters, such as flow rate of CFA acetone solution, antisolvent flow rate, overall flow rate, CFA concentration and precipitation temperature, on particle size and size distribution were experimentally investigated. The results indicated that the particle size obviously decreased from 1100 to 630nm with decreasing the CFA solution flow rate from 16 to 2mL/min, and decreased from 450 to 350nm with the decreased temperature from 50 to 5°C. However, with the increase of the antisolvent flow rate at a fixed CFA solution flow rate of 4mL/min, the particle size obviously decreased from 1229nm (20mL/min) to 581nm (60mL/min), and then increased to 698nm (80mL/min). Also, the particle size firstly decreased and then increased with the increase of the overall flow rate and CFA solution concentration. The as-prepared CFA nanoparticles displayed a size-dependent and significantly enhanced dissolution property when compared to raw CFA and commercial spray-dried CFA. This work suggests that the continuous synthesis in a microfluidic reactor is a simple and economic way to prepare pharmaceutical nanoparticles with tunable sizes. [ABSTRACT FROM AUTHOR]