载体-抑晶剂多元体系过饱和环孢素固体分散体的制备及体外溶出研究  

Preparation and in vitro dissolution of supersaturated CsA solid dispersion of carrier-crystal inhibitor multi-component system

作　　者：程伟康 郑华 郝贵周 翟立海 孙勇[1] CHENG Wei-kang;ZHENG Hua;HAO Gui-zhou;ZHAI Li-hai;SUN Yong(School of Pharmacy,Qingdao University,Qingdao Shandong 266071;Shandong New Times Pharmaceutical Co.,Ltd.,Linyi Shandong 273400)

机构地区：[1]青岛大学药学院,山东青岛266071 [2]山东新时代药业有限公司,山东临沂273400

出　　处：《中南药学》2023年第2期380-385,共6页Central South Pharmacy

基　　金：青岛市关键技术攻关及产业化示范项目(No.22-3-3-hygg-25-hy)。

摘　　要：目的 制备载体-抑晶剂多元体系过饱和环孢素固体分散体,并对其进行体外溶出研究。方法 采用热熔挤出技术,分别以HME专用辅料AFFINISOL HPMC 15LV、HPMC 100LV、聚乙烯吡咯烷酮VA64为载体,泊洛沙姆188、羟丙甲纤维素(HPMC E5)、聚乙烯己内酰胺-聚乙酸乙烯酯-聚乙二醇接枝共聚物(Soluplus)为抑晶辅料,制备单元及多元体系固体分散体。利用粉未X射线衍射法(PXRD)与差示扫描量热法(DSC)对其进行物相表征,并通过体外模拟过饱和溶出试验对聚合物的过饱和增溶能力、抑晶剂的抑晶效果进行考察。结果 结果表明,HPMC 100LV型号聚合物在过饱和增溶上具有较强优势。析晶抑制能力表现为泊洛沙姆188> HPMC E5> Soluplus,且抑晶剂联合用量在药物的0.5倍时抑晶效果最优。结论本研究构建了载体-抑晶剂多元体系固体分散体,可为进一步解决难溶性药物在胃肠道析出及过饱和释药系统的开发提供理论指导。Objective To prepare and determine the supersaturated CsA solid dispersion of carrier-crystal inhibitor multi-component system in vitro dissolution. Methods Hot melt extrusion technology was used to prepare unit and multi-system solid dispersion with HME special auxiliary materials AFFINISOL HPMC 15LV, HPMC 100LV and polyvinylpyrrolidone VA64 as carriers;and poloxamer 188,hydroxypropyl methylcellulose(HPMC E5), and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer(Soluplus) as crystal-inhibiting auxiliary materials. PXRD and DSC were used to characterize the phase of the polymer, and the supersaturation solubilization ability of the polymer and the crystal inhibition effect of crystal inhibitor were investigated by in vitro simulated supersaturation dissolution test. Results HPMC 100LV polymer had obvious advantage in supersaturation solubilization.The crystallization inhibition ability was shown as follows: poloxamer 188 > HPMC E5 > Soluplus,and when the combined dosage of crystal inhibitor was 0.5 times of the drug, the crystal inhibition effect was the best. Conclusion The solid dispersion of carrier-crystal inhibitor multicomponent system constructed in this study provides theoretical guidance for gastrointestinal crystallization of insoluble drugs and the development of supersaturated drug delivery system.

关 键 词：过饱和释药系统 固体分散体 多元体系 抑晶 热熔挤出 

分 类 号：R943[医药卫生—药剂学]