1.Coamorphous combinations of poorly water-soluble drugs dabigatran etexilate mesylate and tadalafil for improving dissolution and physical stability
Xingjia BAO ; Xin CHEN ; Shiru WANG ; Yunni LING ; Jianjun ZHANG ; Yuan GAO
Journal of China Pharmaceutical University 2019;50(5):549-559
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.