染料木素滴丸的制备及在比格犬体内药动学考察

Genistein Dropping Pills:preparation and pharmacokinetics study in Beagle dogs

目的:制备染料木素滴丸,提高染料木素口服吸收生物利用度。方法:选择PEG4000占基质百分比、基质与药物质量比及滴距作为主要影响因素,Box-Behnken效应面法筛选染料木素滴丸处方。X粉末衍射法分析染料木素在滴丸中存在状态,测定溶解度和溶出度等。以染料木素胶囊为对比,考察染料木素滴丸在比格犬体内药动学行为。结果:染料木素滴丸最佳处方工艺:PEG4000占基质百分比为49.8%,基质与药物质量比为3.05∶1,滴距为8.0 cm。染料木素在滴丸中转变为无定形状态,溶解度提高至13.58倍,在60 min累积溶出度达94.89%。药动学结果显示染料木素滴丸达峰时间(t_(max))提前至(1.97±0.70)h,达峰浓度(C_(max))和生物利用度分别提高2.87倍和2.49倍。结论:染料木素滴丸处方工艺简单,溶出度和生物利用度得到明显提高。

OBJECTIVE To prepare Genistein Dropping Pills(GDP)to enhance the oral bioavailability of genistein.METHODS Percentage of PEG4000 in matrix,matrix-to-drug ratio and drip distance were selected as major influencing fac-tors.Box-Behnken response surface design method was employed for examining the optimal prescriptions of GDP.Crystal form of genistein in dropping pills was examined by X-ray powder diffraction(XRPD).Solubility and dissolution rate were determined.Taking genistein capsules as reference,pharmacokinetic behavior of GDP in beagle dogs was also explored.RESULTS Optimal prescriptions for GDP:percentage of PEG4000 in matrix 49.8%,matrix-to-drug ratio 3.05∶1 and dropping distance 8.0 cm.Genistein existed as an amorphous form in dropping pills,solubility spiked to 13.58 folds and cumulative dissolution rate attained 94.89%in 60 min.Pharmacokinetics results showed that peak time(t_(max))of GDP advanced to(1.97±0.70)h and peak concen-tration(C_(max))and relative oral bioavailability jumped by 2.87 and 2.49 folds,respectively.CONCLUSION Formulation of GDP is simple.Both dissolution rate and bioavailability obviously improve.