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Preparation, characterization, and pharmacokinetics of rivaroxaban cocrystals with enhanced in vitro and in vivo properties in beagle dogs.
Meng, Yuanyuan; Tan, Fangyun; Yao, Jiaxin; Cui, Yanan; Feng, Yumiao; Li, Zhiping; Wang, Yuli; Yang, Yang; Gong, Wei; Yang, Meiyan; Kong, Xiaolong; Gao, Chunsheng.
Affiliation
  • Meng Y; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
  • Tan F; School of Pharmacy, Guangxi Medical University, Nanning 530000, China.
  • Yao J; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
  • Cui Y; School of Pharmacy, Guangxi Medical University, Nanning 530000, China.
  • Feng Y; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
  • Li Z; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
  • Wang Y; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
  • Yang Y; Pharmaceutical College, Henan University, Kaifeng 475001, China.
  • Gong W; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
  • Yang M; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
  • Kong X; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
  • Gao C; State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.
Int J Pharm X ; 4: 100119, 2022 Dec.
Article in En | MEDLINE | ID: mdl-35663355
ABSTRACT
Rivaroxaban (RIV) is a direct Factor Xa inhibitor anticoagulant, but the oral bioavailability of RIV is estimated to be only 60% due to its poor solubility. The aim of the present study was to improve the solubility and bioavailability of RIV. Five cocrystals-p-hydroxybenzoic acid (HBA), 2,4-dihydroxybenzoic acid (DBA), nicotinamide (NA), isonicotinamide (IA), and succinic acid (SA)-were used as cofomers and were successfully obtained and characterized by powder X-ray diffraction, thermal analysis, and Fourier transform infrared spectra. RIV-DBA and RIV-HBA cocrystals showed obvious improvements in solubility, dissolution (under sink conditions), and intrinsic dissolution rates versus RIV. Moreover, the dissolution of RIV-HBA, RIV-DBA, and RIV-SA cocrystals under non-sink conditions showed obvious "spring and parachute" patterns. The in vitro permeability levels in a Caco-2 cell model of RIV-DBA and RIV-IA cocrystals were significantly improved versus RIV. Pharmacokinetic studies in beagle dogs showed that RIV-DBA and RIV-HBA cocrystals had higher bioavailability than RIV. The enhancements in solubility and bioavailability indicate the potential of RIV cocrystals as a better candidate for the treatment of thrombosis versus RIV.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Prognostic_studies Language: En Journal: Int J Pharm X Year: 2022 Document type: Article Affiliation country:
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Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Prognostic_studies Language: En Journal: Int J Pharm X Year: 2022 Document type: Article Affiliation country: