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Improving the dissolution behaviors and bioavailability of abiraterone acetate via multicomponent crystal forms

文献类型：期刊论文

作者Yang, Zeen1,2; Yang, Yinghong1,2; Xia, Mengyuan1,2; Dai, Wenjuan2; Zhu, Bingqing2; Mei, Xuefeng1,2
刊名INTERNATIONAL JOURNAL OF PHARMACEUTICS
出版日期2022-02-25
卷号614页码:9
关键词Abiraterone acetate Cocrystal Crystal structure Dissolution Bioavailability
ISSN号0378-5173
DOI10.1016/j.ijpharm.2022.121460
通讯作者Zhu, Bingqing(zhubingq@simm.ac.cn) ; Mei, Xuefeng(xuefengmei@simm.ac.cn)
英文摘要Abiraterone acetate (ABA), the first-line drug for the treatment of metastatic castration resistant prostate cancer (mCRPC), is administered at a high daily dosage of 1000 mg due to its poor solubility, and its fasted absolute oral bioavailability is estimated to be less than 10%. In this work we have focused on developing multicomponent forms with improved dissolution behaviors and bioavailability. Two salts of ABA with malonic acid (ABA-MA) and saccharin (ABA-SAC), and five cocrystals with trans-aconitic acid (ABA-TAA), 1-hydroxy-2-naphthoic acid (ABA-1HNA), pyrocatechol (ABA-PCA), resorcinol (ABA-RES) and hydroquinone (ABA-HDE) were successfully obtained. Their crystal structures were elucidated by single crystal X-ray diffraction, and these multicomponent forms were fully characterized by powder X-ray diffraction, thermal analysis and Fourier Transform Infrared spectra. Among them, ABA-TAA cocrystal shows substantial enhancements both in the solubility and intrinsic dissolution rates in different buffer solutions. In the meantime, we unexpectedly found the gelation of ABA-MA salt and ABA-SAC salt in pH 2.0 buffer solution. The gel-like materials generated on the surface of drug will suppress the release of ABA. Moreover, in vivo pharmacokinetic study on beagle dogs was conducted for ABATAA cocrystal preparation and ABA commercial product, and ABA-TAA cocrystal preparation shows enhanced absorption. These advantages in dissolution behaviors and bioavailability demonstrate the potential of ABA-TAA cocrystal to be a better candidate for the treatment of mCRPC compared with ABA.
WOS关键词COCRYSTAL ; POLYMORPHS ; FOOD ; DRUG
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000773638800005
出版者ELSEVIER
源URL[http://119.78.100.183/handle/2S10ELR8/299854]  
专题中国科学院上海药物研究所
通讯作者Zhu, Bingqing; Mei, Xuefeng
作者单位1.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Pharmaceut Analyt & Solid State Chem Res Ctr, 555 Zuchongzhi Rd, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Yang, Zeen,Yang, Yinghong,Xia, Mengyuan,et al. Improving the dissolution behaviors and bioavailability of abiraterone acetate via multicomponent crystal forms[J]. INTERNATIONAL JOURNAL OF PHARMACEUTICS,2022,614:9.
APA Yang, Zeen,Yang, Yinghong,Xia, Mengyuan,Dai, Wenjuan,Zhu, Bingqing,&Mei, Xuefeng.(2022).Improving the dissolution behaviors and bioavailability of abiraterone acetate via multicomponent crystal forms.INTERNATIONAL JOURNAL OF PHARMACEUTICS,614,9.
MLA Yang, Zeen,et al."Improving the dissolution behaviors and bioavailability of abiraterone acetate via multicomponent crystal forms".INTERNATIONAL JOURNAL OF PHARMACEUTICS 614(2022):9.

入库方式： OAI收割

来源：上海药物研究所

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