氯雷他定包合物水凝胶的制备及药效学评价

Preparation and Pharmacodynamic Evaluation of Hydrogel Containing Loratadine Inclusion Compound

以包封率为评价指标,采用单因素试验优化了氯雷他定的羟丙基-β-环糊精包合物的处方及制备工艺,并通过傅里叶变换红外光谱和单晶X射线衍射分析结果确证了包合物的形成。继续将优化的包合物加至卡波姆凝胶基质中制成透皮用水凝胶,并以制品透过离体大鼠皮肤的体外渗透性能为考察指标,筛选了卡波姆的型号和浓度以及促透剂的种类和浓度。结果显示,采用1.54%卡波姆981为凝胶基质、3%蓖麻油聚烃氧酯为促透剂的包合物水凝胶,在体外显示出较高的渗透性。进一步采用2,4-二硝基氟苯诱导的变应性接触性皮炎(ACD)小鼠为模型,以市售氯雷他定片为对照,考察了本品和不含促透剂的包合物水凝胶的药效。结果表明,相较于模型组,本品能使小鼠耳肿胀度与病理损伤评分显著下降(P<0.05),且与氯雷他定片的药效无显著性差异(P>0.05)。此外,本品与不含促透剂的包合物水凝胶的药效也存在显著差异(P<0.05)。

The formulation and preparation process of hydroxypropyl-β-cyclodextrin inclusion compound of loratadine were optimized by single factor test with encapsulation rate as an evaluation index.According to the results of Fourier transform infrared spectroscopy and single crystal X-ray diffraction analyses,the formation of the inclusion compound was confirmed.Then the optimized inclusion compound was added to the carbomer matrix to make the transdermal hydrogel.And with the in vitro permeability of the product through excised rat skin as an indicator,the grade and concentration of carbomer and the type and concentration of penetration enhancer were screened.The results showed that the inclusion compound-containing hydrogel with 1.54%of carbomer 981 as gel matrix and 3%of castor oil polyurethane EL35 as penetration enhancer showed high permeability in vitro.Furtherly,2,4-dinitrofluorobenzene-induced atopic contact cermatitis(ACD)mice were used as the model,with commercially available loratadine tablets as the control,the efficacies of this product and inclusion compound-containing hydrogel without penetration enhancer were investigated.The results showed that compared with the model group,the hydrogel with 3%of EL35 can significantly reduce the ear swelling and pathological damage scores of mice(P<0.05),and there were no significant differences between the hydrogel and tablets in efficacy(P>0.05).In addition,the efficacy of the final gel with 3%of EL35 was significant different from that of the hydrogel without penetration enhancer(P<0.05).