当归多糖铁胃内滞留缓释片的制备及其犬体内药动学

Preparation of the Angelica sinensis polysaccharide-iron complex floating sustained-release tablets and evaluation of its pharmacokinetics in dogs

目的:制备当归多糖铁胃内滞留缓释片(APIC-FSRT),考察其体外释放度,漂浮性能及制剂在犬体内的药动学。方法:以丙烯酸树脂Ⅱ、羟丙基甲基纤维素、聚维酮等为辅料,全粉末直接压片,制备了日给药2次的当归多糖铁缓释片,考察其在人工胃液中的漂浮性,以及在0.1mol.L-1盐酸溶液中的释放度。建立火焰原子吸收光谱法测定血清中药物浓度,采用DAS2.0统计软件估算Beagle犬服用对照组(力蜚能组)和受试试剂后的各个药动学参数,进行统计学分析。结果:所得胃滞留缓释片累积释放百分率符合Higuchi方程。在犬体内药动学参数为AUC0-t=6.0±1.0,MRT=7.4±0.5,Cmax=1.026±0.332,缓释片与力蜚能组比较,相对生物利用度为134%。结论:当归多糖铁胃内滞留缓释片制备工艺简单,缓释效果明显,与受试制剂比有显著差异。

OBJECTIVE To prepare Angelica sinensis polysaccharide-iron complex floating sustained-release tablets （APIC FSRT） and to evaluate its cumulative release ratio, floating properties in vitro and pharmacokinetics in Beagle dogs. METHODS The tablets were prepared using acrylic resin Ⅱ , HPMC, PVP and so on as excipients. And the tablet was prepared by direct compression. The floating properties in artificial gastric juice and the dissolution of the tablets in 0. 1 mol· L^-1 HCL solution was measured. The serum drug concentration in Beagle dogs was measured by AAS. The parameters of control groups and A- PIC groups in Beagle dogs were evaluated and analyzed statistically by DAS 2. 0 software. RESULTS The releasing rate of the tablets was conformed to Higuehi equation. The pharmaeokinetic parameters of APIC in dogs showed that the AUC（0-t）= 6. 0 ± 1.0, MRT = 7. 4 ± 0. 5, Cmax = 1. 026 ± 0. 332, the relative bioavailability of the tablets was 134%. CONCLUSION The study was found to be effective in the process of Angelicez sinensis polysaecharide-iron complex floating sustained-release tablets. The cunmlative release ratio was eligible, and the tablets produced a relatively flat serum drug concentration in vivo compared with the control groups.