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Physico-mechanical and Stability Evaluation of Carbamazepine Cocrystal with Nicotinamide

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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.

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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.

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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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Authors and Affiliations

  1. Division of Product Quality and Research, Center of Drug Evaluation and Research, Food and Drug Administration, White Oak, LS Building 64, Room 1070, 10903 New Hampshire Ave, Silver Spring, Maryland, 20993-002, USA

    Ziyaur Rahman, Cyrus Agarabi, Ahmed S. Zidan, Saeed R. Khan & Mansoor A. Khan

  2. Faculty of Pharmacy, Zagazig University, Zagazig, Egypt

    Ahmed S. Zidan

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  1. Ziyaur Rahman
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  2. Cyrus Agarabi
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  3. Ahmed S. Zidan
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  4. Saeed R. Khan
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  5. Mansoor A. Khan
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Correspondence to Mansoor A. Khan.

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Rahman, Z., Agarabi, C., Zidan, A.S. et al. Physico-mechanical and Stability Evaluation of Carbamazepine Cocrystal with Nicotinamide. AAPS PharmSciTech 12, 693–704 (2011). https://doi.org/10.1208/s12249-011-9603-4

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