曲安奈德益康唑乳剂型凝胶的研究

发布时间：2018-03-25 20:04

  本文选题：曲安奈德　切入点：硝酸益康唑　出处：《重庆医科大学》2014年硕士论文

【摘要】：曲安奈德益康唑乳膏是由杨森-Cilag制药公司开发的一种复方皮肤外用制剂，国内生产厂家为西安杨森制药有限公司。主要用于治疗皮肤真菌性疾病，如皮炎、湿疹、体癣、手足癣等。该复方制剂上市剂型目前只有乳膏，而没有以卡波姆为凝胶基质的乳剂型凝胶。为使剂型多样化，本文对原剂型乳膏进行了剂型改进，改变为乳剂型凝胶，在外观性状、油腻感、涂抹后美观等方面有了较大改善，提高了患者用药的依从性。 本文的主要内容包括：（1）对曲安奈德益康唑乳剂型凝胶进行了处方筛选及制备工艺研究；（2）进行了曲安奈德益康唑乳剂型凝胶的质量研究；（3）考察了曲安奈德益康唑乳剂型凝胶的稳定性；（4）开展了曲安奈德益康唑乳剂型凝胶的体外经皮渗透性和刺激性研究。 参照市售乳膏，，本文首先进行了处方设计，确定了原辅料种类，并考察和筛选了辅料的用量。由单因素实验结果，确定了影响乳剂型凝胶外观性状和稳定性的主要因素有丙二醇、乙醇、液体石蜡、辛酸癸酸聚乙二醇甘油酯和司盘-80，以外观性状、离心试验、药物晶体析出情况为指标，进行正交试验，优选处方。对工艺参数乳化转速、温度和时间进行考察，确定了最佳制备工艺。 采用HPLC法，建立了含量测定方法，曲安奈德和硝酸益康唑分别在4.78～86.04μg/ml和49.86～897.48μg/ml浓度范围内呈良好线性关系，回收率、精密度和溶液稳定性均符合要求。考察了曲安奈德益康唑乳剂型凝胶的质量，外观为微白色乳剂型凝胶，pH计测定其平均pH值为5.63，25℃的平均动力黏度为40.5Pa·S，含量、粒度、装量差异、耐寒和耐热试验均符合要求。 对曲安奈德益康唑乳剂型凝胶进行了影响因素、加速和长期稳定性试验考察，发现本品在高温60℃和光照下不稳定，应避光、阴凉保存。30℃±2℃、相对湿度（65±5）%条件下进行加速试验，含量和有关物质的变化在规定范围内。以市售包装，密封、阴凉处放置6个月，样品各指标均无明显变化。说明该处方和工艺对于生产研究有一定的参考价值。 对曲安奈德益康唑乳剂型凝胶进行了体外经皮渗透性研究，与市售品乳膏相比，各取样点和平均累积渗透量无显著差异，初步判定两者的有效性无明显差别。同时还考察了曲安奈德益康唑乳剂型凝胶的皮肤刺激性，结果表明，对家兔皮肤无刺激，有较好的安全性。
[Abstract]:Triamcinolone acetonide econazole cream is a compound skin preparation developed by Yang Sen -Cilag Pharmaceutical Company. The domestic manufacturer is Xi'an Yang Sen Pharmaceutical Co., Ltd. It is mainly used to treat skin fungal diseases, such as dermatitis, eczema, tinea corporis, etc. Tinea of hand and foot etc. At present, there is only cream, but no gel with carbomer as gel matrix. In order to diversify the dosage form, this article has improved the dosage form of the original dosage form cream, changed it into emulsion gel, The appearance, greasy feeling and beauty after smear were improved greatly, and the compliance of the patients was improved. The main contents of this paper include: (1) screening of the formulation and preparation process of triamcinolone acetonide econazole emulsion gel; (2) study on the quality of triamcinolone acetonide econazole emulsion gel; (3) investigation of triamcinolone acetonide econazole gel. The in vitro transdermal permeability and irritation of triamcinolone acetonide econazole emulsion gel were studied. With reference to the market cream, the prescription was designed to determine the type of raw and auxiliary materials, and the dosage of excipients was investigated and screened. The main factors affecting the appearance and stability of emulsion gel are propylene glycol, ethanol, liquid paraffin, caprylic acid polyethylene glycol glyceride and Span-80. The main factors affecting the appearance and stability of emulsion gel are propylene glycol, ethanol, liquid paraffin, sebacic acid polyethylene glycol glyceride and Span-80. Orthogonal test was carried out to optimize the formulation. The optimum preparation process was determined by investigating the emulsification speed, temperature and time of the process parameters. A method for the determination of triamcinolone acetonide and econazole nitrate was established by HPLC. The linear range of triamcinolone acetonide and econazole nitrate was 4.78 渭 g/ml and 49.86 渭 g/ml, respectively. The quality of traamcinolone acetonide econazole emulsion gel was investigated. The average dynamic viscosity of triamcinolone acetonide econazole emulsion gel pH meter with average pH value of 5.63 鈩

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