A simultaneous differential scanning calorimetryeFourier transform infrared(DSCeFTIR)microspectroscopy was used to quickly investigate the co-crystal formulation between anhydrous theophylline(TP)and anhydrous citric ...A simultaneous differential scanning calorimetryeFourier transform infrared(DSCeFTIR)microspectroscopy was used to quickly investigate the co-crystal formulation between anhydrous theophylline(TP)and anhydrous citric acid(CA)in a one-step procedure.The raw materials of TP andCA,aswell as the intactTPeCA co-crystal prepared by slow solvent evaporation were also respectively examined by this approach.The result indicates that the TPeCA cocrystal formulation was easily induced using this DSCeFTIR technique.The thermaldependent changes in three-dimensional FTIR spectral contour profiles were started from 165C to induce the co-crystal formation of TPeCA,which was prior to the endothermic peak at 173C found in the conventional DSC curve.Beyond 165C,several new IR absorption peaks at 3515,3124,1730,1710,1677,1648,1552 and 1265 cm1 corresponding to unique IR spectral peaks of intact TPeCA co-crystal were observed.The DSCeFTIR microspectroscopic results also evidenced the dimeremonomer transition of CA,but there were no markedly changes for TP or intact TPeCA co-crystal before its fusion.This strongly implies that the DSCeFTIR technique giving spectroscopic and thermodynamic information could simultaneously induce and identify the TPeCA co-crystal formation and phase transition of samples.Different storage conditions affecting the stability of both physical mixture and ground mixture of TPeCA were also determined.The physicalmixture of TPeCA after storing at 55C/75%RH condition for one day was fast transformed to TPeCA co-crystal,indicating that TPeCA co-crystal was easily induced under accelerated storage condition.While the co-crystal formed from TPeCA ground mixture was stable in both 25C/75%RH and 55C/75%RH conditions.展开更多
基金This work was supported by National Science Council,Taipei,Taiwan(NSC 100-2320-B-264-001-MY3).
文摘A simultaneous differential scanning calorimetryeFourier transform infrared(DSCeFTIR)microspectroscopy was used to quickly investigate the co-crystal formulation between anhydrous theophylline(TP)and anhydrous citric acid(CA)in a one-step procedure.The raw materials of TP andCA,aswell as the intactTPeCA co-crystal prepared by slow solvent evaporation were also respectively examined by this approach.The result indicates that the TPeCA cocrystal formulation was easily induced using this DSCeFTIR technique.The thermaldependent changes in three-dimensional FTIR spectral contour profiles were started from 165C to induce the co-crystal formation of TPeCA,which was prior to the endothermic peak at 173C found in the conventional DSC curve.Beyond 165C,several new IR absorption peaks at 3515,3124,1730,1710,1677,1648,1552 and 1265 cm1 corresponding to unique IR spectral peaks of intact TPeCA co-crystal were observed.The DSCeFTIR microspectroscopic results also evidenced the dimeremonomer transition of CA,but there were no markedly changes for TP or intact TPeCA co-crystal before its fusion.This strongly implies that the DSCeFTIR technique giving spectroscopic and thermodynamic information could simultaneously induce and identify the TPeCA co-crystal formation and phase transition of samples.Different storage conditions affecting the stability of both physical mixture and ground mixture of TPeCA were also determined.The physicalmixture of TPeCA after storing at 55C/75%RH condition for one day was fast transformed to TPeCA co-crystal,indicating that TPeCA co-crystal was easily induced under accelerated storage condition.While the co-crystal formed from TPeCA ground mixture was stable in both 25C/75%RH and 55C/75%RH conditions.
