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

Authors

  • Mao Wang,

    1. Novartis-MIT Center for Continuous Manufacturing, Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
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  • Gregory C. Rutledge,

    1. Novartis-MIT Center for Continuous Manufacturing, Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
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  • Allan S. Myerson,

    1. Novartis-MIT Center for Continuous Manufacturing, Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
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  • Bernhardt L. Trout

    Corresponding author
    1. Novartis-MIT Center for Continuous Manufacturing, Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
    • Novartis-MIT Center for Continuous Manufacturing, Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139. Telephone: +617-258-5021; Fax: +617-253-2272
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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 IQ1/2 (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. © 2011 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:1178–1188, 2012

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