Coamorphous combinations of poorly water-soluble drugs dabigatran etexilate mesylate and tadalafil for improving dissolution and physical stability
10.11665/j.issn.1000-5048.20190507
- VernacularTitle:共无定形体系改善低水溶性药物达比加群酯甲磺酸盐和他达拉非的溶出行为及稳定性
- Author:
Xingjia BAO
1
;
Xin CHEN
;
Shiru WANG
;
Yunni LING
;
Jianjun ZHANG
;
Yuan GAO
Author Information
1. 中国药科大学中药学院
- Publication Type:Journal Article
- Keywords:
dabigatran etexilate mesylate;
tadalafil;
coamorphous;
dissolution property;
physical stability
- From:
Journal of China Pharmaceutical University
2019;50(5):549-559
- CountryChina
- Language:Chinese
-
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.
