地西泮胶束溶液的制备及其释放性能评价  

Preparation and release performance of diazepam micellar solution

作　　者：徐桂林[1] 刘新国[1] 徐辉甫[1] 彭倩倩 XU Gui-lin;LIU Xin-guo;XU Hui-pu;PENG Qian-qian(The First Hospital of Wuhan,Wuhan 430022)

机构地区：[1]武汉市第一医院,武汉430022

出　　处：《中南药学》2022年第11期2593-2597,共5页Central South Pharmacy

基　　金：武汉市第一医院院内课题(No.2019Y28)。

摘　　要：目的 制备载地西泮泊洛沙姆188胶束,以改善地西泮水溶性,考察该纳米胶束的理化性质及体外释放。方法 采用薄膜水化法制备地西泮的泊洛沙姆188胶束溶液。通过透射电镜、激光粒径分析、凝胶柱分离、高相液相色谱等方法考察地西泮胶束的粒子形态、大小、粒径分布、表面ζ电位、药物包封率及载药量等指标,以及在pH 7.2~7.4生理性环境中的体外释药行为,据此对其质量与释药特征进行评价。结果 所制备的地西泮胶束粒子成形良好,外形呈球形或近球形,分布均匀,平均粒径为(6.53±0.81)nm,表面ζ电位平均值为(-2.88±1.03)mV,无聚集现象,平均包封率为(74.8±1.51)%,平均载药量为(2.32±0.05)%。体外释放试验显示地西泮胶束在PBS溶液(pH 7.2~7.4)前段释药较快,6 min累积释药率为32%,此后稳定持续释放,3 h累积释药量接近药物总量85%,累积释放曲线的动力学方程拟合结果表明胶束包封对地西泮释放具有一定缓释作用。结论 胶束包封能有效解决地西泮水溶性问题,同时药物释放相较注射剂更加平稳,为解决地西泮溶解性问题提供了一种行之有效的技术方案。Objective To prepare diazepam-loaded poloxamer 188 micelles to improve its poor water solubility and determine the physicochemical properties and in vitro release of the nanomicelles.Methods Peloxam 188 micelle solution of diazepam was prepared by the thin-film hydration method.The morphology,size,particle size distribution,surface ζ-potential,encapsulation rate,and drug loading capacity of diazepam micelles were determined by transmission electron microscopy,laser particle size analysis,gel column separation,and HPLC.The in vitro drug release behavior in the physiological environment of pH 7.2~7.4 was analyzed,and its quality and drug release characteristics were evaluated based on the above-examined indexes.Results The diazepam micelle particles prepared in this experiment were well-formed and spherical or subspherical.The average particle size was (6.53±0.81) nm,the average surface ζ potential was (-2.88±1.03) mV,and the average encapsulation rate was (74.8±1.51)%.There was no aggregation of the micellar solution,and the average drug loading of micellar particles was (2.32±0.05)%.The in vitro release test showed that diazepam micelles released faster in the first part of PBS solution (pH 7.2~7.4),with a cumulative release rate of 32% at 6 min.Thereafter,the release became stable and continuous,and the 3 h cumulative release amount was close to 85% of the total encapsulated drug.The fitting of the kinetic equation of the cumulative release profile indicated that micelle encapsulation caused the sustained release of diazepam.Conclusion Micelle encapsulation can effectively improve the poor water solubility of diazepam,and the drug release in micellar solution is more stable than that of injection.Therefore,the research provides an effective way to improve of diazepam solubility.

关 键 词：地西泮 溶解性 胶束 药物释放 

分 类 号：R94[医药卫生—药剂学]