药学学报, 2019, 54(1): 22-28
引用本文:
宋莎, 俞洪珍, 朱春柳, 段年秀, 俞淼荣, 凌云, 甘勇. 可形成过饱和胶束的环孢素A渗透泵片的研究[J]. 药学学报, 2019, 54(1): 22-28.
SONG Sha, YU Hong-zhen, ZHU Chun-liu, DUAN Nian-xiu, YU Miao-rong, LING Yun, GAN Yong. Cyclosporin A osmotic pump tablets which can form supersaturated micelles[J]. Acta Pharmaceutica Sinica, 2019, 54(1): 22-28.

可形成过饱和胶束的环孢素A渗透泵片的研究
宋莎1,2, 俞洪珍2, 朱春柳2, 段年秀1,2, 俞淼荣2, 凌云1, 甘勇2
1. 南昌大学药学院, 江西 南昌 330066;
2. 中国科学院上海药物研究所, 上海 201203
摘要:
环孢素A(cyclosporine A,CsA)水溶性差,制约了其口服吸收。本文制备了CsA/Soluplus/SDS复合物,其水化后可形成CsA/Soluplus/SDS过饱和胶束(CsA/Soluplus/SDS supersaturated micelles,CSS-SM);并进一步制备了CSS-SM渗透泵片(CSS-SM-T)。CSS-SM粒径为156 nm,CsA包封率和载药量分别为89.0%和17.5%。CSS-SM-T在体外具有零级释药特征。Beagle犬药动学实验(动物实验均按照中国科学院上海药物研究所实验动物管理和使用委员会的相关要求进行)表明:CsA普通渗透泵片口服几乎无吸收;与市售制剂新山地明软胶囊相比,CSS-SM-T口服生物利用度虽略有下降[相对生物利用度为(85.1 ±47.4)%],但血药浓度波动小,在体内呈明显缓释特征,预示毒性更低。因此,CSS-SM-T为难溶性药物口服缓控释制剂的设计开发提供了一种新的研究思路。
关键词:    环孢素A      过饱和胶束      渗透泵片      药动学      缓释和控释     
Cyclosporin A osmotic pump tablets which can form supersaturated micelles
SONG Sha1,2, YU Hong-zhen2, ZHU Chun-liu2, DUAN Nian-xiu1,2, YU Miao-rong2, LING Yun1, GAN Yong2
1. Pharmacy College of Nanchang University, Nanchang 330066, China;
2. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Abstract:
The poor solubility of cyclosporine A (CsA) in water limits its oral absorption. We prepared CsA/Soluplus/SDS complex, which can form CsA/Soluplus/SDS supersaturated micelles (CSS-SM) after hydration. Then, We further prepared CSS-SM osmotic pump tablets (CSS-SM-T). CSS-SM had a particle size of 156 nm, where in encapsulation efficiency and drug loading efficiency of CsA were 89.0% and 17.5%, respectively. CSS-SM-T achieved zero-level drug release in vitro. Pharmacokinetic data from Beagle dogs (all animal experiments were conducted under the guidelines approved by the Institutional Animal Care and Use Committee of the Shanghai Institute of Materia Medica, Chinese Academy of Sciences) indicated that CsA in the ordinary osmotic pump tablets was hardly absorbed after orally administered; despite slightly lower bioavailability[relative bioavailability:(85.1 ±47.4)%] than that of Sandimmum Neoral, CSS-SM-T displayed lower fluctuations in CsA plasma concentration and obvious sustained-release characteristics in vivo, implying lower toxicity. Therefore, CSS-SM-T provides a new research idea for the design and development of oral sustained-and controlled-release preparations of poorly water-soluble drugs.
Key words:    cyclosporine A    supersaturated micelle    osmotic pump tablet    pharmacokinetics    sustained-and controlled-release   
收稿日期: 2018-10-16
DOI: 10.16438/j.0513-4870.2018-0939
基金项目: 国家自然科学基金资助项目(81573378,81773651);中国科学院战略性先导科技专项(XDA12050307).
通讯作者: 凌云,Tel/Fax:86-791-86361839,E-mail:lyly803@163.com;甘勇,Tel:86-21-20231000-1423,Fax:86-21-20231000-1424,E-mail:ygan@simm.ac.cn
Email: lyly803@163.com;ygan@simm.ac.cn
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