Characterization of co-amorphous carvedilol-maleic acid system prepared by solvent evaporation

The aim of this study was to enhance the solubility and stability of the water-insoluble drug carvedilol (CAR) with maleic acid (MLE) to create a co-amorphous system by a solvent evaporation method. Phase diagrams of co-amorphous CAR-MLE, constructed from peak height in the Fourier-transform infrared (FTIR) spectra and the glass transition temperature (Tg) from differential scanning calorimetry (DSC) measurements, revealed that the optimal molar ratio of CAR to MLE was 2:1. The FTIR spectra indicated that the secondary amine-derived peak of CAR and the carboxy group-derived peak of MLE disappeared in the CAR:MLE (2:1) co-amorphous system. DSC measurements showed that the endothermic peaks associated with the melting of CAR and MLE disappeared and a Tg at 43 degrees C was apparent. Furthermore, the solubility of CAR tested using the shaking flask method for 24 h at 37 degrees C was 1.2 mu g/mL, whereas that of the co-amorphous system was approximately three times higher, at 3.5 mu g/mL. Finally, the stability was evaluated by powder- X-ray diffraction at 40 degrees C; no clear diffraction peaks originating from crystals were observed in the amorphous state until after approximately three months of storage. These results indicate that co-amorphization of CAR with MLE improved the solubility of CAR while maintaining its stability in an amorphous form.

Automated summary

The aim of this study was to enhance the solubility and stability of the water-insoluble drug carvedilol (CAR) with maleic acid (MLE) to create a co-amorphous system. The optimal molar ratio of CAR to MLE was found to be 2:1. The co-amorphous system showed improved solubility of CAR and maintained stability in an amorphous form.