芎芷石膏汤可溶性微针的制备、表征及体外透皮性能研究

Study on preparation,characterization and in vitro transdermal properties of Xiongzhi shigao decoction soluble microneedles

目的制备芎芷石膏汤可溶性微针,并进行表征及体外透皮性能考察。方法采用两步离心法制备芎芷石膏汤可溶性微针,并从基质溶液流动性、微针成形性、针尖硬度等方面评价其成形性和机械性能。以该可溶性微针的活性成分(绿原酸、阿魏酸、羌活醇、欧前胡素、藁本内酯、异欧前胡素)为考察指标,从外观形态、机械强度、溶解性能、皮肤屏障恢复性能、载药量进行表征,并采用Franz扩散池法考察其体外透皮性能。结果本研究所制备的芎芷石膏汤可溶性微针针尖呈圆锥形,分布均匀且粗细相同,机械性能良好;针尖部分可在刺入大鼠皮肤2 h后几乎全部溶解,且皮肤屏障恢复性能良好;微针中绿原酸、阿魏酸、羌活醇、欧前胡素、藁本内酯、异欧前胡素的载药量分别为每片(87.04±1.12)、(67.69±1.23)、(20.65±0.17)、(35.00±0.11)、(153.83±0.21)、(23.52±0.50)μg。体外透皮实验结果显示,该微针中6种活性成分72 h的累积释放率分别为36.94%、56.72%、19.36%、57.98%、11.06%、35.19%。结论本研究成功制备了芎芷石膏汤可溶性微针,其成形性、机械性好,背衬柔韧,可促进药物透皮吸收。

OBJECTIVE To prepare Xiongzhi shigao decoction soluble microneedles,characterize it and investigate its transdermal properties in vitro.METHODS Two-step centrifugal method was used to prepare Xiongzhi shigao decoction soluble microneedles.The formability and mechanical property of the microneedles were evaluated from aspects of stroma fluidity,microneedle formability,needle hardness,etc.The appearance,mechanical strength,dissolution performance,skin barrier recovery performance and drug loading of the prepared microneedles were characterized by using active components of the soluble microneedle(chlorogenic acid,ferulic acid,notopterol,imperatorin,ligustilide,isoimperatorin)as indicators.The in vitro transdermal performance was investigated by Franz diffusion cell.RESULTS The soluble microneedle tips of Xiongzhi shigao decoction prepared in this study were conical,evenly distributed and of the same thickness,with good mechanical properties;the tip of the needle could be almost completely dissolved after being penetrated into the skin of rats for 2 hours,and the skin barrier recovery performance was good;the drug loading of chlorogenic acid,ferulic acid,notopterol,imperatorin,ligustilide and isoimperatorin were(87.04±1.12),(67.69±1.23),(20.65±0.17),(35.00±0.11),(153.83±0.21)and(23.52±0.50)μg per patch respectively.The results of in vitro transdermal study showed that cumulative release rates of 6 active components in this microneedle after 72 hours were 36.94%,56.72%,19.36%,57.98%,11.06%and 35.19%,respectively.CONCLUSIONS Xiongzhi shigao decoction soluble microneedles are prepared successfully in this study and have good formability,mechanical properties and pliable backing,which can significantly promote the transdermal drug delivery.