화학공학소재연구정보센터
Journal of Supercritical Fluids, Vol.55, No.3, 1070-1078, 2011
Formulation development of Carbamazepine-Nicotinamide co-crystals complexed with gamma-cyclodextrin using supercritical fluid process
The objective of the present study was to formulate and characterize co-crystals of Carbamazepine (CBZ) and Nicotinamide (NCT) and inclusion complexes of these co-crystals with gamma-cyclodextrin (CD). Gas anti-solvent method of supercritical fluid process (SCF) was used as the method of preparation. Formulations were evaluated by dissolution studies, differential scanning calorimetry, hot stage microscopy, scanning electron microscopy, H-1 NMR and X-ray powder diffraction. The dissolution studies show a 2.5-fold increase in dissolution rate in the case of co-crystals and a 40-fold increase when co-crystals were complexed with CD. A lower melting point (160 degrees C) was observed in the case of co-crystals and the exothermic peaks were missing for pure CBZ and co-crystals when they were complexed with CD. The absence of the melting peaks indicates complete complexation. Electron microscopy picture shows the absence of crystallinity in case of inclusion complexes and also the change in crystal structure for CBZ and NCT in the case of co-crystals. X-ray powder diffraction patterns of co-crystals and inclusion complexes were distinct from the starting materials and the shift in peaks of H NMR confirmed intermolecular hydrogen bonding and complexation. (C) 2010 Elsevier B.V. All rights reserved.