ABSTRACT
@#Dabigatran etexilate mesylate(DE)and tadalafil(TD)are BCS class II drugs with poor water solubility. 〓 In this study coamorphization technique was used to improve their solubilities/dissolutions and hence to enhance their oral absorptions. The coamorphous DE-TD were prepared by solvent-evaporation method and characterized by PXRD, DSC, FTIR and TGA. In addition, dissolution behavior and physical stability were also investigated. Only halo pattern and a single Tg of 119 °C was observed on the PXRD and DSC of the co-evaporated product, respectively, indicating the formation of coamorphous DE-TD. FTIR result suggested that a hydrogen bond was probably formed between N-H group of DE and C==O group of TD. In comparison to crystalline counterparts, coamorphous DE-TD showed a significantly improved intrinsic dissolution rate and prolonged supersaturation time in intrinsic dissolution and supersaturation dissolution studies, respectively. No crystallization was observed under affecting factors testing(30 days)as well as long-term and accelerated stability testing(90 days)for the prepared coamorphous DE-TD under 25°C/60%RH or 40°C/75%RH, while amorphous DE crystalized at 10 days under 25 ℃/75% RH.
ABSTRACT
In order to research the related substances of dabigatran etexilate mesylate,seven related compounds were synthesized and the related detection methods were established (Using XBridge C18 as the column,methanol-0.01mol/L potassium dihydrogen phosphate as the mobile phase Gradient elution,detection wavelength of 310 nm).The solvents and the injection volume were also screened.Results showed that the established method could separate the dabigatran etexilate mesylate and seven compounds completely,and the reproducibility was good and the accuracy was high,which was suitable for the detection of the related substances of dabigatran etexilate mesylate.