【作者】 孙春梅；

【导师】 张汝华； 王洪光；

【作者基本信息】 沈阳药科大学 ， 药物制剂， 2002， 硕士

【摘要】 熔融高速搅拌法制备缓释微丸以其特有的工艺特点，近年来越来越多地受到人们的关注，是制备缓释微丸有效的生产方法之一。在最简单的形式中，起始物料在混合器中混合，随着过程的继续，由于摩擦产生的热而使温度升高，粘合剂融化作为液体粘合剂。通过进一步地混合碰撞，颗粒结聚，最终形成微丸。关于熔融高速搅拌法制备微丸已有文献报道，为了给生产提供依据、提高药物制剂的生产水平，本文以自制的高速搅拌制粒机对模型药物的微丸制备工艺及其对产品质量的影响进行了较为全面的考察和研究。 本实验在参照了有关资料的基础上，自制了适用于实验室研究及小批量生产的高速搅拌制粒机，本装置操作方便，易于控制，容易清洗。本次实验的目的是进行盐酸普萘洛尔复方制剂的研究。由于各种条件的限制，最终只形成了普萘洛尔缓释微丸，氢氯噻嗪制成了普通片而不是微丸。 不同药物由于粉体性质如结晶形状、流动性、粘结能力等的不同，往往不同药物用同一处方或制丸工艺不同时，成丸效果不同。而组成微丸的辅料种类、数量和性质不同会极大地影响微丸的成型及微丸的质量。针对模型药物的性质，选择了硫酸钙为稀释剂，氢化蓖麻油为粘合剂。 此次工艺的进行分为三个阶段。第一阶段：采用高速搅拌制粒机制备了普萘洛尔空白丸心。对其制备工艺及影响因素(粘合剂的种类、转桨速度、载药量、混合时间等)进行了考察，并进行了优化，选出了较佳的工艺参数。投料量为100g，其中粘合剂是硫酸钙量的26％，温度为87℃，转速为350rpm，制备时间为6min，制备沈阳药科大学硕士学位论文 摘要出了圆整、密实、堆密度大的空白丸心。 第二阶段在同一设备中将其制备工艺与包衣技术相结合，将普素洛尔与粘合剂的混合物以一定的速度喷洒到空白丸心上，使其形成含药量适宜的药丸。对其影响因素进行了考察，最终选定了包衣温度为 87．3 C，转速为 250rpm，空白丸心与普蔡洛尔与粘合剂的量比为 50：40：15。 第三阶段将阻滞材料包在含药丸上，形成12小时的缓释微丸。对影响缓释微丸释放的各种因素进行了考察，选定的包衣材料（硫酸钙：氢化蓖麻油）的量比为1：l，包衣量为含药丸量的50％。 采用相似因子祛研究了普蒂洛尔缓释微丸的稳定性，结果表明缓释微丸在高温、高湿、光照及加速实验条件下基本稳定，经家犬体内药动学研究表明，缓释微丸的Tmx为3．54 ’J’时，tl／2为3．2 ’J’时，相对生物利用度为235．1％。 论文的第二部分是氢氯噬嗓普通片的制备研究。对处方进行了正交设计，筛选出最佳处方，达到预期要求，在30分钟氢氯噬嗓的溶出达到80％，对影响其释放的各种因素进行了考察。并采用HPLC法对普蔡洛尔和氢氯噬嗓两种成分进行了初步的分析研究。 本次实验研究了缓释微丸的成丸过程，采用了一种适用于模型药物的制备方法，达到了预期的要求。可以看出，熔融高速搅拌制丸法制各缓释微丸效果良好，为将来的工业化大生产提供了可行的参考。更多还原

【Abstract】 Melt pelletization in a high speed mixer has its unique character, one of the techniques which manufacture pelletized products. Pellets are of great interest to the people more and more. It is one of the common and effective methods in producing sustained-release pellets. In its simplest form, melt pelletization proceeds by mixing the starting materials with a binder which is solid at ambient temperature and melts or softens at relative low temperatures. By operation of the mixture, the temperature is raised because of the development of heat caused by friction. The binder melts and acts like a liquid binder. By further agigation wet agglomerates are formed. Melt pelletization in a high shear mixer has been reported before, to provide basis for pharmaceutical industry and raising the level of pharmaceutical products, the process variable and effects of these parameters on the performance of the end products were investigated using self-made high shear mixer in the article.Based on previous experiments,a laboratory scale high speed mixer was self-made. It is convenient to operate the mixer and control the mixing process. It is easy to clean this equipment. The purpose of the present work was about the studies on the compound recipe Propranolol sustained-release pellets. Because of some reasons we preparedPropranolol sustained-release pellets and Hydrochlorothiazide conventional tables not pellets.Drugs have different micromeritics property for example crystal state, flowbility, binding force, if they are manufactured based on the same formulation or the same process technology, the performance of the pellet is different. The different types, amounts and properties of the experients affect the possibility of the pellets and the quality of the pellets. Based on the property of the model drug, we selected Calcium Sulfate as dilute, Hydrogenated Castor Oil as binder.There were three phases in the process. The first phase: the variables (the different kinds of binder, the impeller speed, product load, and massing time) 100g product load, 87centigrade product temperature, 350rpm impeller speed, the massing time was 7min.The results showed that pellets made had advantages of good sphericity, high strength and high bulk density.The second phase was used combing melt pelletization in the same high-shear mixer with coating technique to obtain pellets with high drug content inside. The mixer containing Propranolol and binder was sprayed on the surface. The variables were investigated and the optimal parameters of process were found under certain condition. They were 86.5 centigrade coating temperature, 350rpm impeller speed. The amount radio of pellets and Propranolol and binder was 50:40:15.The last phase was the coating process which was performed by coating hydrophobic and hydrophilic materials to obtain 12 hour sustained-release pellets. The results indicated that the ideal sustain-release behavior and good release reproductivity were achieved using coating formulation .The amount radio of Calcium Sulfate and Hydrogenated Castor Oil was 1:1, the total amount of coating materials was 50 percent of the amount of the drug pellets.The stability of Propranolol sustained-release pellets were studiedABSTRACTusing the method of fit factor. The drug content and release stability of sustained-release pellets were good under the condition of high temperature, high humidity and strong light. The pharmacokinetics of pellets in dogs indicated that the Tmax was 3.54h, t1/2 was 3.2h, and relative bioavaility was 235.1%.The second part of this paper was about the preparation of Hydrochlorothiazide. The formulation variables were optimizated by orthogonal design. The release of Hydrochlorothiazide in 30min was 80 percent of the total amount and this formulation was equivalent to the standard. HPLC method were used to detect Propranolol and Hydrochlorothiazide.This article discussed the form mechanism of pellet and adopted a process that was applicable to the model drug. The results in t更多还原