AAPS PharmSciTech

, Volume 12, Issue 2, pp 693–704 | Cite as

Physico-mechanical and Stability Evaluation of Carbamazepine Cocrystal with Nicotinamide

  • Ziyaur Rahman
  • Cyrus Agarabi
  • Ahmed S. Zidan
  • Saeed R. Khan
  • Mansoor A. Khan
Research Article

Abstract

The focus of this investigation was to prepare the cocrystal of carbamazepine (CBZ) using nicotinamide as a coformer and to compare its preformulation properties and stability profile with CBZ. The cocrystal was prepared by solution cooling crystallization, solvent evaporation, and melting and cryomilling methods. They were characterized for solubility, intrinsic dissolution rate, chemical identification by Fourier transform infrared spectroscopy, crystallinity by differential scanning calorimetry, powder X-ray diffraction, and morphology by scanning electron microscopy. Additionally, mechanical properties were evaluated by tensile strength and Heckel analysis of compacts. The cocrystal and CBZ were stored at 40°C/94% RH, 40°C/75% RH, 25°C/60% RH, and 60°C to determine their stability behavior. The cocrystals were fluffy, with a needle-shaped crystal, and were less dense than CBZ. The solubility profiles of the cocrystals were similar to CBZ, but its intrinsic dissolution rate was lower due to the high tensile strength of its compacts. Unlike CBZ, the cocrystals were resistant to hydrate transformation, as revealed by the stability studies. Plastic deformation started at a higher compression pressure in the cocrystals than CBZ, as indicated by the high yield pressure. In conclusion, the preformulation profile of the cocrystals was similar to CBZ, except that it had an advantageous resistance to hydrate transformation.

Key words

carbamazepine cocrystal mechanical property nicotinamide stability 

Notes

Acknowledgment

The authors would like to thank the Oak Ridge Institute for Science and Education (ORISE) for supporting the post doctoral research program. The authors also thank Mr. Alan Carlin for helping with the FTIR spectrum.

Disclaimer

The views and opinions expressed in this paper are only those of the authors and do not necessarily reflect the views or policies of the FDA.

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Copyright information

© American Association of Pharmaceutical Scientists 2011

Authors and Affiliations

  • Ziyaur Rahman
    • 1
  • Cyrus Agarabi
    • 1
  • Ahmed S. Zidan
    • 1
    • 2
  • Saeed R. Khan
    • 1
  • Mansoor A. Khan
    • 1
  1. 1.Division of Product Quality and Research, Center of Drug Evaluation and ResearchFood and Drug AdministrationSilver SpringUSA
  2. 2.Faculty of Pharmacy, Zagazig UniversityZagazigEgypt

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