Improving relative bioavailability of dicumarol by reducing particle size and adding the adhesive poly(fumaric-co-sebacic) anhydride.
Improving relative bioavailability of dicumarol by reducing particle size and adding the adhesive poly(fumaric-co-sebacic) anhydride.
复制标题
通过减小粒径和添加粘合剂聚（富马酸-癸二酸）酐来提高双香豆素的相对生物利用度。
DOI：
10.1023/a:1024474609667
复制
发表时间：
2003
影响因子：
3.7
通讯作者：
Mathiowitz,E
中科院分区：
文献类型：
--
作者：
Thanos,CG;Liu,Z;Reineke,J;Edwards,E;Mathiowitz,E
目的。本研究考察了粒径减小和生物粘附对双双酚醇溶出度和相对生物利用度的影响。配方是通过多种方法生产的，包括一种新的技术来减小颗粒尺寸，以及用聚（富马酸-共癸二酸）酸酐p（FA:SA）相转化来制造纳米球。结果：体外实验结果表明，微粉化制剂和包封的p（FA:SA）纳米微球的溶出度均有所提高。在体内，通过进一步减小颗粒大小，喷雾干燥制剂的相对生物利用度在大鼠中增加了17%，在猪中增加了72%。与喷雾干燥药物相比，生物胶p（FA:SA）配方也提高了相对生物利用度，大鼠和猪的相对生物利用度分别提高了55%和96%。此外，p（FA:SA）配方延长了两种动物的tmax，降低了cmax。这项工作证明了粒径和生物黏附对提高杜芦酚口服生物利用度的重要性。
Purpose. This study was carried out to show the effect of particle size reduction and bioadhesion on the dissolution and relative bioavailability of dicumarol.Methods. Formulations were produced by a variety of methods including a novel technique to reduce particle size as well as phase inversion with poly(fumaric-co-sebacic)anhydride p(FA:SA) to create nanospheres. Drug was administered to groups of pigs and rats via oral gavage of a suspension, and dicumarol concentration in the blood was measured using a double extraction technique.Results.In vitroresults showed improved dissolution in both the micronized formulation and the encapsulated p(FA:SA) nanospheres.In vivo,relative bioavailability of a spray-dried formulation was increased by 17% in the rat and 72% in the pig by further reduction in particle size. The bioadhesive p(FA:SA) formulation also improved relative bioavailability over the spray-dried drug, increasing it by 55% in the rat and 96% in the pig. Additionally, the p(FA:SA) formulation prolonged Tmaxand decreased Cmaxin both species.Conclusion. This work demonstrates the importance of particle size and bioadhesion to improve oral bioavailability of ducumarol.