活络效灵凝胶贴膏剂的制备及体外透皮吸收研究

Preparation of Huoluo Xiaoling gel plaster and its transdermal penetration in vitro

活络效灵丹为临床常用活血止痛疗效确切的经典名方,为了使其药效直达病灶以提高疗效,该研究优化了活络效灵凝胶贴膏剂的制备工艺,并进一步评价其体外透皮吸收性能,为其开发利用提供科学依据。以初黏力、持黏力、感官评分为评价指标,通过单因素试验和Box-Behnken响应面法确定凝胶贴膏剂的基质用量。建立UPLC同时测定贴膏剂中丹参素、阿魏酸、丹酚酸B、丹酚酸A、藁本内酯、丹参酮ⅡA、11-羰基-β-乳香酸(11-keto-β-boswellic,KBA)、3-乙酰-11-羰基-β-乳香酸(3-acetyl-11-keto-β-boswellic acid,AKBA)8种有效成分的含量。采用改良Franz扩散池法评价并比较不加挥发油、直接加入挥发油和加入挥发油微乳的凝胶贴膏剂的体外透皮吸收性能。结果表明,活络效灵凝胶贴膏剂基质的最优处方为NP7001.35 g、甘油7.00 g、微粉硅胶1.25 g、羧甲基纤维素钠0.20 g、酒石酸0.06 g、甘羟铝0.04 g;贴膏剂中8种有效成分的质量分数依次为0.48、0.014、0.95、0.39、0.57、0.055、0.35、0.97 mg·g^(-1);体外透皮吸收实验结果发现,直接加入挥发油或加入挥发油微乳均可促进有效成分的透皮吸收,药物透过规律符合零级方程或Higuchi方程。通过最优处方制备的凝胶贴膏剂外观性状好,黏附性好,剥离无残留,具有骨架型缓释制剂的特性,便于减少给药次数,为活络效灵丹外用新剂型的开发奠定了基础。

Huoluo Xiaoling Dan is a classical prescription commonly used for blood circulation and pain relief in clinic with obvious effects.To make it directly treat lesion and improve the effect,this research optimized the preparation process of Huoluo Xiaoling gel paste and further evaluated its in vitro transdermal absorption performance,so as to provide a scientific basis for its development and utilization.Using primary viscosity,holding viscosity,and sensory score as evaluation indexes,the matrix amount of gel paste was determined by the single factor test and Box-Behnken response surface method.The ultra-performance liquid chromatography(UPLC)method was established to determine the content of eight active ingredients,including Danshensu,ferulic acid,salvianolic acid B,salvianolic acid A,ligustilide,tanshinoneⅡA,11-keto-β-boswellic(KBA),and 3-acetyl-11-keto-β-boswellic acid(AKBA).A mo-dified Franz diffusion cell method was used to evaluate and compare the absorption properties of the gel paste without volatile oil and with volatile oil microemulsion.The results showed that the optimal prescription for Huoluo Xiaoling gel paste matrix was NP700(1.35 g),glycerol(7.00 g),micropowder silica gel(1.25 g),sodium carboxymethyl cellulose(0.20 g),tartaric acid(0.06 g),and glyceryl aluminum(0.04 g).The mass fractions of eight active ingredients in the paste were successively 0.48,0.014,0.95,0.39,0.57,0.055,0.35,and 0.97 mg·g^(-1).The results of the in vitro transdermal absorption test showed that the addition of the volatile oil or the volatile oil microemulsion promoted the transdermal absorption of the active ingredients,and the law of drug penetration conformed to the zero equation or the Higuchi equation.The gel paste prepared by the optimal prescription has good appearance and adhesion,with no residue,and has the characteristics of skeletal slow-release preparation,which is easy to reduce the number of administration,la-ying a foundation for the development of new external dosage forms of Huoluo Xiaoling Dan.