Production and characterization of carbamazepine nanocrystals by electrospraying for continuous pharmaceutical manufacturing
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Mao_CBZ nanocrystals_0708-combined.pdf
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0960fbd3557bc09867eeda7f93671998
Author(s)
Wang, Mao
Rutledge, Gregory C.
Myerson, Allan S.
Trout, Bernhardt L.
Date Issued
December 2011
Journal
Journal of Pharmaceutical Sciences
Publisher
Wiley Blackwell
Citation
Wang, Mao, Gregory C. Rutledge, Allan S. Myerson, and Bernhardt L. Trout. Production and Characterization of Carbamazepine Nanocrystals by Electrospraying for Continuous Pharmaceutical Manufacturing. Journal of Pharmaceutical Sciences 101, no. 3 (March 20, 2012): 1178-1188.
Version
Author's final manuscript
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[superscript 1/2] (I, electrical current; Q, flow rate), 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 90°C, which is above the transition temperature, 78°C, for the enantiotropic CBZ form III and form I. The solubility and dissolution rates of CBZ nanocrystals increased significantly as compared with 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.
MIT Department
Novartis-MIT Center for Continuous Manufacturing
Massachusetts Institute of Technology. Department of Chemical Engineering
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DOI of Published Version
https://doi.org/10.1002/jps.23024
