Jie Liu, Qingyue Liu, Zhi Zhang, Wenzhi Yang, Haiying Li
{"title":"基于疏水性和固体分散技术提高贝扎布酸的溶解度和生物利用度","authors":"Jie Liu, Qingyue Liu, Zhi Zhang, Wenzhi Yang, Haiying Li","doi":"10.1007/s12247-025-09984-5","DOIUrl":null,"url":null,"abstract":"<div><h3>Purpose</h3><p>Bezafibrate (BZF), a fibrates lipid-lowering drug, is primarily used in clinical practice for hyperlipidemia with significantly elevated triglycerides (TG). Its effect on reducing TG is more pronounced than that of statins, compensating for the shortcomings of statin medications. However, BZF is a BCS class II drug due to its low solubility in water and its poor oral bioavailability. To enhance the solubility and bioavailability of BZF, a co-amorphous complex comprising BZF and a hydrotrope was prepared.</p><h3>Methods</h3><p>Arginine (Arg) was selected as a hydrotrope for BZF. The BZF-Arg co-amorphous complex was prepared by the freeze-drying method and characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray powder diffraction (XRPD), and differential scanning calorimetry (DSC). Moreover, the complex was evaluated by stability test, in vitro release experiment and pharmacokinetic study.</p><h3>Results</h3><p>The characterization results demonstrated that the formation of hydrogen bonds between BZF and Arg, and the crystalline state of the drug was transformed into the amorphous state in the BZF-Arg complex. Moreover, the complex exhibited good stability and better release in vitro. The pharmacokinetic study revealed that the peak concentration (C<sub>max</sub>) and the area under the curve (AUC<sub>0→36</sub>) of the BZF-Arg complex were significantly improved compared to those of the BZF suspension, following the relative bioavailability of 255%.</p><h3>Conclusion</h3><p>BZF-Arg co-amorphous complex prepared by the combination of hydrotropy and solid dispersion technique provides a promising strategy for enhancing the solubility and bioavailability of BZF.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"20 2","pages":""},"PeriodicalIF":2.7000,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Enhancement of Solubility and Bioavailability of Bezafibrate Based on Hydrotropy and Solid Dispersion Technique\",\"authors\":\"Jie Liu, Qingyue Liu, Zhi Zhang, Wenzhi Yang, Haiying Li\",\"doi\":\"10.1007/s12247-025-09984-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Purpose</h3><p>Bezafibrate (BZF), a fibrates lipid-lowering drug, is primarily used in clinical practice for hyperlipidemia with significantly elevated triglycerides (TG). Its effect on reducing TG is more pronounced than that of statins, compensating for the shortcomings of statin medications. However, BZF is a BCS class II drug due to its low solubility in water and its poor oral bioavailability. To enhance the solubility and bioavailability of BZF, a co-amorphous complex comprising BZF and a hydrotrope was prepared.</p><h3>Methods</h3><p>Arginine (Arg) was selected as a hydrotrope for BZF. The BZF-Arg co-amorphous complex was prepared by the freeze-drying method and characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray powder diffraction (XRPD), and differential scanning calorimetry (DSC). Moreover, the complex was evaluated by stability test, in vitro release experiment and pharmacokinetic study.</p><h3>Results</h3><p>The characterization results demonstrated that the formation of hydrogen bonds between BZF and Arg, and the crystalline state of the drug was transformed into the amorphous state in the BZF-Arg complex. Moreover, the complex exhibited good stability and better release in vitro. The pharmacokinetic study revealed that the peak concentration (C<sub>max</sub>) and the area under the curve (AUC<sub>0→36</sub>) of the BZF-Arg complex were significantly improved compared to those of the BZF suspension, following the relative bioavailability of 255%.</p><h3>Conclusion</h3><p>BZF-Arg co-amorphous complex prepared by the combination of hydrotropy and solid dispersion technique provides a promising strategy for enhancing the solubility and bioavailability of BZF.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>\",\"PeriodicalId\":656,\"journal\":{\"name\":\"Journal of Pharmaceutical Innovation\",\"volume\":\"20 2\",\"pages\":\"\"},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2025-04-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Pharmaceutical Innovation\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s12247-025-09984-5\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Pharmaceutical Innovation","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s12247-025-09984-5","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Enhancement of Solubility and Bioavailability of Bezafibrate Based on Hydrotropy and Solid Dispersion Technique
Purpose
Bezafibrate (BZF), a fibrates lipid-lowering drug, is primarily used in clinical practice for hyperlipidemia with significantly elevated triglycerides (TG). Its effect on reducing TG is more pronounced than that of statins, compensating for the shortcomings of statin medications. However, BZF is a BCS class II drug due to its low solubility in water and its poor oral bioavailability. To enhance the solubility and bioavailability of BZF, a co-amorphous complex comprising BZF and a hydrotrope was prepared.
Methods
Arginine (Arg) was selected as a hydrotrope for BZF. The BZF-Arg co-amorphous complex was prepared by the freeze-drying method and characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray powder diffraction (XRPD), and differential scanning calorimetry (DSC). Moreover, the complex was evaluated by stability test, in vitro release experiment and pharmacokinetic study.
Results
The characterization results demonstrated that the formation of hydrogen bonds between BZF and Arg, and the crystalline state of the drug was transformed into the amorphous state in the BZF-Arg complex. Moreover, the complex exhibited good stability and better release in vitro. The pharmacokinetic study revealed that the peak concentration (Cmax) and the area under the curve (AUC0→36) of the BZF-Arg complex were significantly improved compared to those of the BZF suspension, following the relative bioavailability of 255%.
Conclusion
BZF-Arg co-amorphous complex prepared by the combination of hydrotropy and solid dispersion technique provides a promising strategy for enhancing the solubility and bioavailability of BZF.
期刊介绍：
The Journal of Pharmaceutical Innovation (JPI), is an international, multidisciplinary peer-reviewed scientific journal dedicated to publishing high quality papers emphasizing innovative research and applied technologies within the pharmaceutical and biotechnology industries. JPI''s goal is to be the premier communication vehicle for the critical body of knowledge that is needed for scientific evolution and technical innovation, from R&D to market. Topics will fall under the following categories:
Materials science,
Product design,
Process design, optimization, automation and control,
Facilities; Information management,
Regulatory policy and strategy,
Supply chain developments ,
Education and professional development,
Journal of Pharmaceutical Innovation publishes four issues a year.
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