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目的:制备长春胺缓释微丸并考察其在Beagle犬体内的药动学特征,为非p H依赖性释放的长春胺缓释制剂研发提供参考。方法:制备酒石酸丸芯,采用流化床混悬液上药法制备长春胺缓释微丸。Beagle犬随机分成2组,单剂量双周期交叉口服长春胺缓释微丸与普通片,采用HPLC测定血药浓度,流动相0.02 mol·L-1磷酸二氢钾-乙腈(70∶30,用磷酸调节p H2.3),检测波长268 nm,比较各制剂的药动学参数。结果:长春胺缓释微丸与普通片在Beagle犬血浆中Cmax分别为(1 147.40±554.50),(1 506.10±327.44)μg·L-1;Tmax分别为(2.38±0.25),(1.63±0.25)h;MRT分别为(6.75±2.44),(3.19±0.73)h;AUC0-t分别为(4 766.76±1 740.26),(3 906.81±686.53)μg·h·L-1。长春胺缓释微丸较普通片的相对生物利用度122%,体内外相关性良好。结论:与普通片相比,长春胺缓释微丸在Beagle犬体内吸收较慢,平均滞留时间为普通片的2倍以上,生物利用度显著提高,说明该处方可实现药物在胃肠道中非p H依赖性释放。
OBJECTIVE: To prepare vincamine sustained-release pellets and study their pharmacokinetics in Beagle dogs, and to provide a reference for the development of sustained-release preparations of vinpocetine which are not dependent on p H. Methods: Tartaric acid pellets were prepared and the vinblastine sustained-release pellets were prepared by fluid-bed suspension method. Beagle dogs were randomly divided into two groups. One dose of two cycles of crossover administration of vincamine sustained-release pellets and ordinary tablets, the determination of plasma concentration by HPLC, the mobile phase 0.02 mol·L-1 potassium dihydrogen phosphate - acetonitrile (70:30, with Phosphorylation p H2.3), the detection wavelength was 268 nm, the pharmacokinetic parameters of each preparation were compared. Results: The C max values of vincamine sustained release pellets and common tablets in Beagle dogs were (1 147.40 ± 554.50) and (1 506.10 ± 327.44) μg · L -1, respectively. The Tmax were (2.38 ± 0.25) and (1.63 ± 0.256 h). MRT was (6.75 ± 2.44) and (3.19 ± 0.73) h, respectively; AUC0-t were (4766.76 ± 1 740.26) and (3906.81 ± 686.53) μg · h · L-1, respectively. The relative bioavailability of vincamine sustained-release pellets compared with ordinary tablets was 122%, and the correlation was good in vivo and in vitro. Conclusion: Compared with the common tablets, the slow release of vincamine sustained-release pellets in Beagle dogs is slower, the average residence time is more than 2 times the ordinary tablets, bioavailability was significantly increased, indicating that the prescription can be achieved in the gastrointestinal tract of non-drug p H-dependent release.