曲安奈德益康唑乳膏的制备及安全性研究

发布时间：2018-11-25 15:15

【摘要】：曲安奈德益康唑乳膏既有抗菌的作用,也有抗炎的作用,临床主要用于湿疹患者的治疗,也用于治疗皮炎患者。曲安奈德益康唑乳膏曲安奈德含量为0.1%,硝酸益康唑含量为1%,是由二者组成的复合制剂。曲安奈德属中强效的糖皮质激素,既有抗炎症的功效,同时具有抗过敏和抗毒活性,做为外用制剂应用时具有系统吸收少的特点,临床用于治疗各种非感染性炎症性皮肤病。 在处方工艺研究的前期研究中,首先建立了有关物质高效液相色谱法分析方法。方法学研究证明,确定的有关物质测定方法可以有效的分离各杂质,且专属性良好。 在处方工艺研究的前期研究中,建立了含量测定高效液相色谱法分析方法。线性关系研究结果表明,曲安奈德在30.24～70.56μg/mL浓度范围内浓度与色谱峰面积呈现良好的线性关系,益康唑在0.3012～0.7028mg/mL浓度范围内浓度与色谱峰面积呈现良好的线性关系。同时,方法学研究结果表明精密度、回收率试验均符合要求。 另外,在处方研究中,以产品性状、含量、有关物质等参数为考察指标,进行了处方单因素考察,并对主要工艺参数进行研究,最后通过正交优化试验进行了优化,并确定最优处方。 同时,本论文对制得的曲安奈德益康唑乳膏进行了质量研究,拟定初步质量标准。样品稳定性考察结果表明：加速试验(温度40℃±2℃、湿度RH75%±5%)考察6个月,分别于1、2、3、6月取样检测,与零月数据比较,各检测项目无明显变化。试验结果表明本品在加速条件下放置6个月质量稳定；长期试验(温度25℃±2℃、湿度RH60%±10%)考察12个月,分别于3、6、9、12月取样检测,各检测项目与零月数据比较,无明显变化,说明本品基本稳定,质量稳定可靠。 最后,对曲安奈德益康唑乳膏的体外透皮性及安全性进行了研究。透皮研究发现本品在24小时内透过皮肤进入接受液中的药物量都极少,但均测到了皮肤中的滞留量,说明本品可有效产生局部效应而避免全身作用。而安全性评价研究表明本品与市售品曲安奈德益康唑乳膏及市售派瑞松对家兔完整皮肤及破损皮肤有轻度的刺激性,末次给药后第八天红斑消退,两者比较未见明显差别：两者均无过敏性。
[Abstract]:Triamcinolone acetonide econazole cream has both antibacterial and anti-inflammatory effects. It is mainly used in the treatment of eczema and dermatitis. The contents of triamcinolone acetonide and econazole nitrate were 0.1 and 1, respectively. Triamcinolone acetonide is a kind of medium effective glucocorticoid, which has not only anti-inflammatory effect, but also anti-allergic and antitoxic activity. In the previous study of prescription technology, a HPLC method was established for the analysis of related substances. Methodological studies show that the determined method can effectively separate impurities, and the specificity is good. In the previous study of prescription technology, a HPLC method for content determination was established. The results showed that the concentration of triamcinolone acetonide in the range of 30.24 渭 g/mL and 70.56 渭 g/mL showed a good linear relationship with the chromatographic peak area. There was a good linear relationship between the concentration of econazole and the chromatographic peak area in the range of 0.3012~0.7028mg/mL concentration. At the same time, the methodological research results show that the precision and recovery test are in line with the requirements. In addition, in the study of prescription, the parameters such as product character, content and related substances were used as the index, the single factor of prescription was investigated, and the main technological parameters were studied. Finally, the optimization was carried out by orthogonal optimization test. The optimal prescription was determined. At the same time, the quality of triamcinolone acetonide econazole cream was studied. The results of the stability test showed that the accelerated test (temperature 40 鈩，

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