盐酸青藤碱自溶性微针的制备及其体外经皮渗透性能考察

Preparation and in Vitro Percutaneous Permeability of Sinomenine Hydrochloride-loaded Self-dissolving Microneedles

目的:优选盐酸青藤碱自溶性微针的处方工艺,并考察微针对盐酸青藤碱经皮渗透性能的影响。方法:采用浇注法制备盐酸青藤碱微针,以成型性和机械性为指标筛选可达到最佳载药量的处方,并对制备出的微针进行表征。采用改良Franz扩散池考察载药凝胶和微针的经皮渗透效果。运用HPLC检测盐酸青藤碱含量,流动相甲醇-0.1%磷酸盐水溶液(18∶82),检测波长263 nm。结果:最佳处方聚乙烯吡咯烷酮、硫酸软骨素、盐酸青藤碱质量分数分别为50%,15%,35%。制得的盐酸青藤碱微针针形完整、机械强度良好,能够穿刺铝箔和离体的大鼠皮肤;载药微针组和载药凝胶组的48 h累积渗透量分别为(80 738.41±1 354.72),(15 210.02±288.57)μg·cm^(-2),渗透速率依次为(1 627.40±28.68),(321.72±15.20)μg·cm^(-2)·h^(-1)。结论:制备的载药自溶性微针机械性和成型性良好。相较于载药凝胶,盐酸青藤碱微针能够更加有效地实现经皮渗透,可改善青藤碱透皮制剂的透皮性能。

Objective： To optimize preparation process of sinomenine hydrochloride-loaded selfdissolving microneedles and to investigate effect of microneedles on transdermal delivery of sinomenine hydrochloride. Method： The microneedles was prepared by casting method. Taking formability and mechanical property of micrneedles as indexes, prescription with optimal drug content was screened out, and its characterization was investigated. In vitro permeation of sinomenine hydrochloride-loaded self-dissolving microneedles and sinomenine hydrochloride-loaded hydrogel were examined by Franz diffusion cell. HPLC was employed to determine the content of sinomenine hydrochloride with mobile phase of methanol-0. 1% phosphate solution（ 18 ∶ 82） and detection wavelength of 263 nm. Result： Optimal prescription was as follows：polyvinylpyrrolidone（ PVP） of 50%, chondroitin sulfate of 15%, sinomenine hydrochloride of 35%. The developed microneedles had regular shapes of needles with good mechanical strength,it can insert into aluminum foil and rat＇s skin. Accumulation permeation amount and rate of sinomenine hydrochloride in microneedles group increased 5. 31 times and 5. 06 times versus hydrogel group, respectively. Conclusion： These prepared microneedles have ideal formability and mechanical property. It provides more effective permeability of sinomenine hydrochloride by comparing with hydrogel group.