Coamorphous combinations of poorly water-soluble drugs dabigatran etexilate mesylate and tadalafil for improving dissolution and physical stability

BAO Xingjia; CHEN Xin; WANG Shiru; LING Yunni; ZHANG Jianjun; GAO Yuan

doi:10.11665/j.issn.1000-5048.20190507

Journal of China Pharmaceutical University > 2019 > 50(5): 549-559. > DOI: 10.11665/j.issn.1000-5048.20190507

BAO Xingjia, CHEN Xin, WANG Shiru, LING Yunni, ZHANG Jianjun, GAO Yuan. Coamorphous combinations of poorly water-soluble drugs dabigatran etexilate mesylate and tadalafil for improving dissolution and physical stability[J]. Journal of China Pharmaceutical University, 2019, 50(5): 549-559. DOI: 10.11665/j.issn.1000-5048.20190507

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Coamorphous combinations of poorly water-soluble drugs dabigatran etexilate mesylate and tadalafil for improving dissolution and physical stability

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〓 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 T_g 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.
- dabigatran etexilate mesylate,
- tadalafil,
- coamorphous,
- dissolution property,
- physical stability

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Coamorphous combinations of poorly water-soluble drugs dabigatran etexilate mesylate and tadalafil for improving dissolution and physical stability

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