Development and evaluation of drug-loaded niosomes fabricated by flow chemistry: A novel vortex tube reactor approach

Continuous flow technology has been increasingly applied in the fabrication of nanoparticle drug delivery systems due to its ability to provide enhanced process control, scalability, and improved uniformity in particle size. Therefore, this study aims to utilize a newly designed flow chemistry vortex tube reactor for the preparation of ketoconazole-loaded niosomes, with the goal of enhancing mixing efficiency and increasing production rates. The experiment was designed using a central composite design to investigate the effects of key preparation parameters, including total flow rate, surfactant concentration, and cholesterol content, on particle size, size distribution, zeta potential, entrapment efficiency, and drug loading percentage. The optimized formulation (Span 80 = 25 mg, Cholesterol = 50 mg) was achieved using a total flow rate of 20 mL/min. The resulting niosomes exhibited a particle size of 212.3 nm, a zeta potential of 40.2 mV, a polydispersity index of 0.282, an entrapment efficiency of 50.84 %, a drug loading of 0.58 %, and a productivity of 70.67 mg/min. Moreover, ketoconazole-loaded niosomes prepared using the newly designed flow chemistry vortex tube reactor demonstrated prolonged inhibition of Candida albicans growth compared to ketoconazole solution. A comparison with batch synthesis revealed that flow chemistry produces smaller particles with a narrower size distribution and significantly improved productivity. These findings indicate the potential for further development of the vortex reactor for industrial-scale production of nanovesicular drug delivery systems.