title: Physico-mechanical and stability evaluation of carbamazepine cocrystal with nicotinamide.
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.
authors: Division of Product Quality and Research, Center of Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland 20993-002, USA.
authors: Ziyaur
authors: Z
authors: Rahman
authors: Cyrus
authors: C
authors: Agarabi
authors: Ahmed S
authors: AS
authors: Zidan
authors: Saeed R
authors: SR
authors: Khan
authors: Mansoor A
authors: MA
authors: Khan
references: J Pharm Sci. 2003 Nov;92(11):2260-71
references: 14603511
references: Int J Pharm. 2002 Oct 10;246(1-2):121-34
references: 12270615
references: Int J Pharm. 2000 Jan 5;193(2):137-46
references: 10606776
references: J Pharm Sci. 1968 May;57(5):802-5
references: 5657539
references: Pharm Res. 2006 Oct;23(10):2381-92
references: 16988890
references: Mol Pharm. 2004 Jan 12;1(1):85-96
references: 15832504
references: Mol Pharm. 2007 May-Jun;4(3):386-400
references: 17497886
references: Int J Pharm. 2006 Aug 31;320(1-2):114-23
references: 16769188
references: Eur J Pharm Biopharm. 2008 Jun;69(2):476-85
references: 18294828
references: Cryst Growth Des. 2008;8(1):14-16
references: 19367342
references: J Pharm Sci. 2007 May;96(5):1147-58
references: 17455346
references: Int J Pharm. 2001 Aug 28;225(1-2):83-96
references: 11489557
references: Mol Pharm. 2006 May-Jun;3(3):362-7
references: 16749868
references: Int J Pharm. 2010 Nov 15;400(1-2):49-58
references: 20801200
references: J Pharm Biomed Anal. 2000 Aug 1;23(1):41-54
references: 10898153
references: AAPS J. 2010 Jun;12(2):158-70
references: 20127529
references: Mol Pharmacol. 1995 Jun;47(6):1189-96
references: 7603459
references: Eur J Pharm Biopharm. 2006 Nov;64(3):360-8
references: 16846725
references: J Control Release. 2000 Jan 3;63(1-2):1-6
references: 10640575
references: J Pharm Sci. 2001 May;90(5):569-79
references: 11288101