Continuous production of celecoxib nanoparticles using a three-dimensional-coaxial-flow microfluidic platform.

Abstract

Increasing the dissolution rate of water insoluble drugs by decreasing the particle size of the drugs into nano-size is a well-known strategy. However, continuous production of drug nanoparticles with uniform particle size is critical for clinical application of the strategy. Here we report a simple microfluidic mixing method that can achieve continuous production of celecoxib nanoparticles with uniform particle size and high dissolution rate. A three-dimensional (3D) coaxial-flow microfluidic device was fabricated by assembling two coaxial aligned borosilicate glass capillaries on a glass slide, and a tapered glass capillary was inserted into another bigger cylindrical one with coaxial alignment. Celecoxib nanoparticles were prepared by the microfluidic device under the turbulent jet regime. The 3D-coaxial-flow pattern and high Reynolds number ensured the extremely short mixing time, consequently, resulted in the high throughput production of drug nanoparticles with uniform particle size. The obtained nanoparticles were spherical in shape, and showed superior dissolution rate compared with the coarse powder both in sink and non-sink conditions. The bioavailability of the water insoluble drug was also significantly improved by the reduction of particle size into nano-size.