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J Pharm Sci. 2017 Jul;106(7):1874-1880. doi: 10.1016/j.xphs.2017.03.045. Epub 2017 Apr 19.

Spray Drying as a Reliable Route to Produce Metastable Carbamazepine Form IV.

Author information

1
EPSRC Centre for Innovative Manufacturing in Continuous Manufacturing and Crystallisation, c/o Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Technology and Innovation Centre, 99 George Street, Glasgow G1 1RD, UK.
2
EPSRC Centre for Innovative Manufacturing in Continuous Manufacturing and Crystallisation, c/o Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Technology and Innovation Centre, 99 George Street, Glasgow G1 1RD, UK. Electronic address: cameron.brown.100@strath.ac.uk.
3
Pure and Applied Chemistry, University of Strathclyde, Glasgow, UK.

Abstract

Carbamazepine (CBZ) is an active pharmaceutical ingredient used in the treatment of epilepsy that can form at least 5 polymorphic forms. Metastable form IV was originally discovered from crystallization with polymer additives; however, it has not been observed from subsequent solvent-only crystallization efforts. This work reports the reproducible formation of phase pure crystalline form IV by spray drying of methanolic CBZ solution. Characterization of the material was carried out using diffraction, scanning electron microscopy, and differential scanning calorimetry. In situ Raman spectroscopy was used to monitor the spray-dried product during the spray drying process. This work demonstrates that spray drying provides a robust method for the production of form IV CBZ, and the combination of high supersaturation and rapid solid isolation from solution overcomes the apparent limitation of more traditional solution crystallization approaches to produce metastable crystalline forms.

KEYWORDS:

PAT; carbamazepine; continuous processing; metastable form; polymorphism; spray drying

PMID:
28431966
DOI:
10.1016/j.xphs.2017.03.045
[Indexed for MEDLINE]
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