Physico-mechanical and stability evaluation of carbamazepine cocrystal with nicotinamide.

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

Research output: Contribution to journalArticlepeer-review

86 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)693-704
Number of pages12
JournalAAPS PharmSciTech
Issue number2
StatePublished - Jun 2011
Externally publishedYes

ASJC Scopus subject areas

  • Pharmaceutical Science


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