丹参酮固体分散体的制备及其体内外评价  

Preparation and in vitro Evaluation of Tanshinones Ternary Solid Dispersions

作　　者：刘文静 蒲君峰[1] 惠娜[1] 钱倩 LIU Wen-jing;PU Jun-feng;HUI Na;QIAN Qian(Department of Pharmacy,Gansu Province Hospital,Lanzhou 730000,China)

机构地区：[1]甘肃省人民医院药剂科,甘肃兰州730000

出　　处：《海峡药学》2021年第1期8-13,共6页Strait Pharmaceutical Journal

摘　　要：目的制备丹参酮固体分散体,并考察其体外溶出度和大鼠体内生物利用度。方法以水溶性高分子材料聚乙二醇6000(PEG6000)及十二烷基硫酸钠(SLS)为载体,采用溶剂-熔融法制备丹参酮固体分散体,测定溶解度及体外溶出度,并应用差示扫描量热分析(DSC)、傅立叶变换近红外光谱分析(FT-NIR)技术表征所制备的固体分散体;采用反相高效液相色谱法(RP-HPLC)测定大鼠口服丹参酮固体分散体后体内药动学行为。结果制备的三元固体分散体能显著增加丹参酮的溶解度,加速其体外溶出。DSC、FT-NIR结果显示,丹参酮在固体分散体中以无定型态或分子状态存在;体内生物利用度实验显示,制备的丹参酮三元固体分散体与二元固体分散体相比,丹参酮的药时曲线下面积(AUC_(0^t))、血药峰浓度(C_(max))显著提高,达峰时间(T_(max))明显提前,其生物利用度提高1.88倍。结论三元固体分散体能显著提高难溶性药物丹参酮的体外溶出度和体内生物利用度。OBJECTIVE To prepare tanshinones solid dispersions,and to investigate the in vitro solubility of tanshinone and the in vivo bioavailability in rats.METHODS The tanshinones solid dispersions,consisting of Polyethylene Glycol 6000(PEG6000),Sodium Lauryl Sulfate(SLS),were prepared by the solvent-melting technique,and research on its solubility and dissolution.Differential Scanning Calorimetry(DSC)and Fourier Transform Near Infrared Spectroscopy(FT-NIR)were used to characterize these systems.RP-HPLC was used to evaluate the pharmacokinetic behavior of rats after oral administration of Tanshinones solid dispersions.RESULTS The in vitro dissolution test showed that the ternary tanshinones solid dispersions can significantly improve the dissolution of tanshinones.The DSC and FT-NIR spectra analysis revealed that TANs SDs was in an amorphous or molecule state.The bioavailability of TANs in ternary SDs showed that the AUC 0^t and C max was significantly increased and T max markedly decreased compared with binary SDs.The bioavailability of TANs in ternary SDs was 1.88 times than that of in binary SDs.CONCLUSION Ternary SDs can be successfully applied to improve the in vitro dissolution and in vivo bioavailability of the poorly soluble drug tanshinones.

关 键 词：丹参酮 固体分散体 体外溶出度 体内生物利用度 

分 类 号：R94[医药卫生—药剂学]