【作者】 魏莉；

【导师】 王东凯；

【作者基本信息】 沈阳药科大学 ， 药剂学， 2005， 硕士

【摘要】 西洛他唑（Cilostazol）属于血小板凝集抑制剂，其口服主要用于治疗稳定性间歇性跛行。该药疗效确切，毒副作用低。为方便患者服药，本文研究制备了西洛他唑口腔崩解片。 本文首先对西洛他唑的溶解度、及表观油/水分配系数等理化性质进行了考察，为处方设计和药剂学研究奠定基础。 西洛他唑味苦，微溶于水，为掩盖其不良味道，并增加其溶解度，在单因素考察的基础上，优化微球形硅胶吸附药物的条件。并用溶液层积工艺进一步提高吸药微球形硅胶的载药量。用SURELEASE水分散体系作为包衣材料制备西洛他唑微囊，包衣粒子增重20％时，可达到较好的掩味效果。 考察了几种辅料的溶解性和压缩成形性，确定了甘露醇，微晶纤维素，交联聚乙烯吡咯烷酮作为口腔速崩片的主要辅料。通过正交试验确定了三者的最佳比例，采用直接压片法制备口腔速崩片，工艺简单重现性好且成本较低。体外溶出度试验结果表明，口腔速崩片中药物的溶出速度要比普通片中药物的溶出速度快。 对制剂进行了初步的质量研究，为质量标准的建立提供根据：确定了以0.3％十二烷基硫酸钠溶液为溶剂，采用分光光度法测定样品的溶出度，用HPLC法检测其含量及有关物质，方法学考察结果表明，检测方法可信，准确。 稳定性试验表明本品在40±2℃，RH75％±5％的加速条件下，保存三个月，在25±2℃，RH60％±10％的条件下，长期试验观察6个月，样品性状、崩解时限、含量等均未发生明显变化，说明西洛他唑原料及所选辅料性质稳定。 建立了HPLC法测定了人血浆中西洛他唑浓度的方法，比较了自制口腔崩解片与市售普通片剂在人体内的药代动力学参数，结果表明二者变化趋势相似，其主要药代动力学参数基本一致（P＞0.05），试验制剂平均相对生物利用度为104.38％；两种片剂的AUC，C_max等效性检验结果证明，自制制剂与参比西洛他唑片为生物等效制剂。更多还原

【Abstract】 Cilostazol is a kind of platelet aggregation inhibitors, and is often administrated orally in the treatment of stable angina cruris. Its therapeutic effects were certain and its side effects and toxicities could be neglected. To make it convenient for the patients to take it, we studied the preparation of Cilostazol fast buccal disintegration tablet in this article.Firstly, the physico-chemistry properties such as dissolubility, apparent oil/water distribution ratio and so on were investigated for the following work of prescription design and pharmaceutical research.Cilostazol is bitter and slightly soluble in water. To cover up its disagreeable taste and promote its solubility, the condition of utilizing microballoons silicagel to absorb the medicine was optimized in accordance with the results of the single factor investigation. And the silicagel’s capacity of absorbing the drug was increased by using in the technology of solution lamination. The disagreeable taste of the drug is well masked when the particals’ weight of the Cilostazol microcapsule which used aqueous dispersion of SURELEASE as its coating materials is increased by 20%.The manitol, cellulose microcrystallisate and crospolyvinylpyrrolidone were chosen as the main adjuvants of the fast buccal disintegrating tablet after the investigating of the solubility and the compress formability of several kinds of adjuvants. And the optimal proportion of the three adjuvants was determined through orthogonal experiments. Finally, the fast buccal disintegrating tablet was prepared using direct compression method whose procedure was simple and the cost was low. It was confirmed by the result of the solution rate experiment in vitro that the solution velocity of fast buccal disintegration tablet was faster than common tablets.The preliminary research of the quality of this preparation was studied which provided basic更多还原