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胶束包封微粒技术:一种解决难溶性药物溶解和生物利用度问题的新方法。

Micelles entrapped microparticles technology: a novel approach to resolve dissolution and bioavailability problems of poorly water soluble drugs.

机构信息

Formulation Research and Development, Natco Research Centre, Natco Pharma Limited, Hyderabad, India.

Centre for Biotechnology, Institute of Science and Technology, Jawaharlal Nehru Technological University Hyderabad, Hyderabad, India.

出版信息

J Microencapsul. 2020 May;37(3):254-269. doi: 10.1080/02652048.2020.1729883. Epub 2020 Feb 19.

Abstract

Aim of this study was to design a solid oral delivery system for a weakly basic drug such as dasatinib (DAS), so as to achieve pH-independent dissolution and improved oral bioavailability. DAS was solubilised using sodium lauryl sulphate as an aqueous micellar system and such a system containing lactose monohydrate as carrier was spray-dried to obtain a solid mass. Subsequently, the DAS-solid was converted into a tablet using conventional tableting methods. The dissolution study revealed pH-independent dissolution over a wide range of pH conditions. An bioavailability testing on rats revealed an improved and AUC. Similarly, viability assay showed a better inhibitory effect of spray-dried dasatinib over the DAS. Micellar solubilisation and spray-drying technology can be approached to resolve poor dissolution and bioavailability of drugs belonging to biopharmaceutical classification system II and III. This technology is amenable to scale-up and has commercial potential.

摘要

本研究旨在设计一种用于弱碱性药物(如达沙替尼)的固体口服递药系统,以实现 pH 无关溶解和提高口服生物利用度。通过使用十二烷基硫酸钠作为水性胶束系统来增溶达沙替尼,并使用含有一水乳糖的该系统作为载体进行喷雾干燥以获得固体物质。随后,使用常规压片方法将达沙替尼固体转化为片剂。溶解研究表明,在广泛的 pH 条件下具有 pH 无关溶解。在大鼠中的生物利用度测试显示出改善的 t1/2 和 AUC。同样,活力测定显示喷雾干燥的达沙替尼对 DAS 具有更好的抑制作用。胶束增溶和喷雾干燥技术可用于解决属于生物药剂学分类系统 II 和 III 的药物的溶解和生物利用度差的问题。该技术适合放大,并具有商业潜力。

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