Microfluidic Fabrication of Monodispersed Pharmaceutical Colloidal Spheres of Atorvastatin Calcium with Tunable Sizes

In this work, monodispersed pharmaceutical colloidal spheres of atorvastatin calcium (AC) with tunable sizes have been synthesized in a microfluidic system at continuous flow conditions. The influences of the key parameters, including the concentration of the AC methanol solution, the overall flow rate, the flow rate of isopropanol, and the flow rate of the AC methanol solution on particle size and size distribution were discussed. The results indicated that the drug concentration and the flow rate could efficiently control the particle size and improve the polydispersity of the resulting particles. The particle size decreased from 760 to 300 nm with an increase in the AC concentration from 30 to 60 mg/mL and significantly increased from 430 to 2500 nm with an increase in the flow rate of the AC methanol solution from 2.7 to 16 mL/min. However, with the increase of the overall flow rate at a fixed flow ratio of 10, the particle size slightly decreased from 240 (10/1 mL/min) to 210 nm (30/3 mL/min) and then dramatically increased to 680 nm (80/8 mL/min). Also, the particle size first decreased and then increased with an increase in the flow rate of isopropanol. The prepared AC colloidal spheres were amorphous and displayed enhanced dissolution rate compared with the commercial AC. This work shows that the continuous synthesis in a microfluidic reactor is a simple and economic way to prepare monodispersed pharmaceutical colloidal particles or nanoparticles with tunable sizes.