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目的制备氨茶碱贴片,并研究其经脐部给药后家兔体内的药动学特征。方法采用流涎工艺制备氨茶碱贴片,以离体大鼠腹部皮肤为透皮屏障,采用改良Franz法优选渗透促进剂。健康家兔分别经灌胃氨茶碱溶液、背部与脐部敷贴氨茶碱贴片后,HPLC测定体内血药浓度,计算药动学参数,评价药动学特征。结果质量分数3%的薄荷脑-丙二醇(1∶1)混合渗透促进剂为药物的最佳渗透促进剂,稳态透皮速率为(9.08±0.21)μg.cm-2.h-1。氨茶碱溶液灌胃、贴剂背部与脐部敷贴后家兔体内的主要药动学参数:ρmax分别为(13.42±1.10)、(4.53±0.39)和(5.77±0.44)μg.mL-1;tmax分别为(1.83±0.29)、(5.67±0.58)和(4.33±0.58)h;AUC0→t分别为(47.65±3.46)、(31.65±4.11)和(39.97±3.14)μg.h.mL-1;t1/2分别为(1.90±0.30)、(2.45±0.07)和(1.90±0.06)h;Ka分别为(2.01±0.55)、(0.33±0.02)和(0.55±0.04)h-1和tlag分别为(0.19±0.04)、(0.59±0.03)和(0.32±0.19)h;以灌胃给药组为对照,背部给药与脐部给药相对生物利用度分别为(67.41±19.11)%、(84.81±18.03)%。结论成功制备了经皮渗透性能良好的氨茶碱贴片。与灌胃给药相比,该贴片经背部、脐部敷贴给药后家兔体内血药峰浓度明显降低,达峰时间延迟;且脐部给药较背部给药生物利用度显著增高,脐部给药有利于氨茶碱经皮吸收。
Objective To prepare aminophylline patch and study its pharmacokinetics in rabbits after umbilical administration. Methods Aminophylline patch was prepared by salivating technology. The skin of the abdomen of rats was transdermal barrier. The modified Franz method was used to optimize permeation enhancer. The healthy rabbits were treated with aminophylline solution by intragastric administration and the aminophylline patch on the back and umbilical respectively. Then the blood concentration in the body was measured by HPLC, the pharmacokinetic parameters were calculated and the pharmacokinetic characteristics were evaluated. Results Menthol-propanediol (1: 1) mixed permeation enhancer with 3% mass fraction was the best penetration enhancer with the steady-state transdermal rate of (9.08 ± 0.21) μg.cm-2.h-1. The main pharmacokinetic parameters of rabbits after the application of aminophylline solution were as follows: ρmax (13.42 ± 1.10), (4.53 ± 0.39) and (5.77 ± 0.44) μg.mL- 1; tmax was (1.83 ± 0.29), (5.67 ± 0.58) and (4.33 ± 0.58) h respectively; AUC0 → t were (47.65 ± 3.46), (31.65 ± 4.11) and (39.97 ± 3.14) μg.h respectively. mL-1 and t1 / 2 were (1.90 ± 0.30), (2.45 ± 0.07) and (1.90 ± 0.06) h, respectively; Ka were 2.01 ± 0.55, 0.33 ± 0.02 and 0.55 ± 0.04 h- 1 and tlag were (0.19 ± 0.04), (0.59 ± 0.03) and (0.32 ± 0.19) h, respectively. The relative bioavailability of dorsal administration and umbilical administration was (67.41 ± 19.11)%, (84.81 ± 18.03)%. Conclusion A transdermal permeable aminophylline patch was successfully prepared. Compared with intragastric administration, the peak concentration of blood plasma of rabbits decreased obviously and the peak time was prolonged after the patch was applied to the back and umbilicals, and the bioavailability was significantly increased , Umbilical administration is conducive to aminophylline percutaneous absorption.