Theophylline–citric acid co-crystals easily induced by DSC–FTIR microspectroscopy or different storage conditions

Hong-Liang Lin, Po-Chun Hsu, Shan-Yang Lin
2013 Asian Journal of Pharmaceutical Sciences  
Anhydrous citric acid DSCeFTIR Storage condition Ground mixture a b s t r a c t 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 and CA, as well as the intact TPeCA co-crystal prepared by slow solvent evaporation were also respectively examined by this approach. The
more » ... sult 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 165 C to induce the co-crystal formation of TPeCA, which was prior to the endothermic peak at 173 C found in the conventional DSC curve. Beyond 165 C, several new IR absorption peaks at 3515, 3124, 1730, 1710, 1677, 1648, 1552 and 1265 cm À1 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 physical mixture of TPeCA after storing at 55 C/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 25 C/75% RH and 55 C/75% RH conditions.
doi:10.1016/j.ajps.2013.07.003 fatcat:4viashysejhl3nurikxqkp6t4q