田蓟苷固体分散体的制备及体内药动学研究

Preparation and in Vivo Pharmacokinetics of Tilianin Solid Dispersions

目的:制备田蓟苷固体分散体(Til-SD),并考察其体内药动学行为。方法:以体外Til累积溶出度为考察指标,采用单因素试验对制备方法、载体的种类、载体与原料比例、制备温度、制备时间分别考察,在单因素试验基础上,采用正交试验设计优化制备工艺。通过差示扫描量热法(DSC)对Til-SD物相进行表征。大鼠灌胃给药后,HPLC法测定Til血药浓度,计算主要药动学参数。结果:采用溶剂-熔融法,载体为Plasdone S-630,Til与载体的比例为1∶7,制备温度为80℃、制备时间为60 min时,制备的Til-SD的累积溶出度较原料药增加最为明显,在溶出30 min时,累积溶出度可达91.1%,较原料药提高了7.4倍多。Til以非晶型状态均匀分散于载体Plasdone S-630中。与Til原料药比较,固体分散体相对生物利用度提高到218.5%。结论:固体分散体可促进Til口服吸收,提高其生物利用度。

Objective To prepare tilianin solid dispersions,and to investigate its in vivo pharmacokinetic behaviors.Methods Taking the cumulative percentage of dissolution in vitro as the index of investigation,taking the preparation technology,type of carrier,the ratio of carrier to raw material,mixing temperature and mixing time were the investigation factors.Based on the single factor experiment,orthogonal experiment design was used to optimize the experiment.Differential Scanning Calorimetry(DSC)was used to characterize the optimal solid dispersion.Rats were given intragastrical administrtaion,after which HPLC was adopted in the plasma concentration determination of tilianin,and main pharmacokinetic parameters were calculated.Results The optimum prepartion process of tilianin solid dispersion prepared is melting-solvent method,when the carrier was Plasdone S-630,the ratio of raw materials to carriers was 1∶7,mixing temperature was 80℃and the mixing time was 60 min,the cumulative dissolution percentage of tilianin solid dispersion can reach 91.1%in 30 min,which is more than 7.4 times higher than tilianin.Tilianin mostly existed in solid dispersion in amorphous form.Compared to tilianin,the bioavailability of tilianin solid dispersions was enhanced to 218.5%,repectively.Conclusion Solid dispersion technology can obviously promote the in vivo absorption of tilianin and enhance its bioavailability.