Production and characterization of carbamazepine nanocrystals by electrospraying for continuous pharmaceutical manufacturing Citation

The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. Abstract: In this paper, an electrospray technique followed by annealing at high temperatures was developed to produce nanocrystals of carbamazepine (CBZ), a poorly water-soluble drug, for continuous pharmaceutical manufacturing process. Electrospraying solutions of CBZ in methanol obeys the expected scaling law of current, which is I~ Q 1/2 , for liquids with sufficiently high conductivity and viscosity. Lower flow rates during electrospraying were preferred to produce smaller diameters of monodisperse, dense CBZ nanoparticles. CBZ nanoparticles were predominantly amorphous immediately after electrospraying. Crystallization of CBZ nanoparticles was accelerated by annealing at high temperatures. CBZ nanocrystals with the most stable polymorph, form III, were obtained by annealing at 90⁰C, which is above the transition temperature, 78⁰C, for the enantiotropic CBZ form III and form I. The solubility and dissolution rates of CBZ nanocrystals increased significantly compared to those of CBZ bulk particles. Therefore, electrospray technology has the potential to produce pharmaceutical dosage forms with enhanced bioavailability and can readily be integrated in a continuous pharmaceutical manufacturing process.