氯硝柳胺纳米悬浮液和涂膜剂的研究

发布时间：2018-03-21 23:03

本文选题：氯硝柳胺　切入点：纳米悬浮液　出处：《华中科技大学》2007年硕士论文　论文类型：学位论文

【摘要】： 氯硝柳胺是一种水杨酰替苯胺类化合物,因杀螺效果好,对人畜毒性低,为WHO唯一推荐使用的杀螺药。但由于氯硝柳胺溶解度小,水中分散度差,因而悬浮率低,限制了其灭螺效果的充分发挥。因此如何增加溶解度和悬浮率,是提高氯硝柳胺灭螺效果的关键问题。药物纳米悬浮液是近几年发展起来的一种纳米载药系统,它能够增加难溶性药物的溶解度和药物溶出速率,提高难溶性药物的药用效果,另外,具有制备工艺简单、载药量高等特点。本文将纳米悬浮液引入氯硝柳胺的制剂研究,对难溶性药物的制剂研究具有一定的参考意义。同时,开展了氯硝柳胺涂膜剂的制剂工艺与质量研究,为氯硝柳胺外用制剂的研究发展开创了新的思路。主要完成的研究工作有: (1)采用高压匀质法,制备了氯硝柳胺纳米悬浮液。考察了润湿剂的种类和用量、助悬剂的种类和用量、载体的种类对悬浮性能的影响,以及匀质压力、循环次数对粒径的影响和该方法的重现性。结果表明,影响药物纳米粒粒径的主要因素是匀质压力和循环次数:随着匀质压力和循环次数的增加,药物纳米悬浮液的粒径呈减小趋势,并呈现良好的分散性。通过对匀质压力及循环次数的控制,可以制得符合粒径要求的氯硝柳胺纳米悬浮液。并且高压匀质法具有高度重现性。另外,表面活性剂的存在,可以在一定程度上抑制纳米颗粒的团聚,维持体系的稳定性。 (2)对用高压匀质法制备的氯硝柳胺纳米悬浮液,进行了表征及理化性质研究。透射电镜显示为球形或近球形颗粒。纳米悬浮液的悬浮率远高于可湿性粉剂。而且,悬浮稳定性提高,悬浮时间明显延长。 (3)为提高氯硝柳胺纳米悬浮液的稳定性,采用喷雾干燥技术制备了氯硝柳胺纳米悬浮液的喷干粉。考察了高压匀质法制备的氯硝柳胺纳米悬浮液喷雾干燥后的性质,图像分析显示为交联状结构。喷干粉中氯硝柳胺的溶解百分率远高于氯硝柳胺原药,悬浮率也高于氯硝柳胺可湿性粉剂,润湿性有了明显改善。而且,悬浮稳定性提高,悬浮时间延长。 (4)进行了氯硝柳胺纳米悬浮液的药效学研究。试验结果表明:在相同条件下,氯硝柳胺纳米悬浮液的灭螺效果是市售可湿性粉剂的2倍;为达到相同的灭螺效果,纳米悬浮液的用药量是市售可湿性粉剂的一半,大大减少了用药量。而且,随着用药量的减少,药物产生的毒副作用相应降低,同时也减少了对环境的污染,这具有较强的实际应用价值。 (5)进行了氯硝柳胺涂膜剂的处方及工艺研究。制成的不含药物的制剂为无色透明、澄清状液体,含有药物的涂膜剂为亮黄色、透明澄清状液体。药物和成膜材料之间无沉淀、变色等配伍禁忌现象发生,易涂展,涂布后具有快干性能,能够形成干燥的薄膜。薄膜具有良好的附着性、均匀性和一定的抗撕裂性,不易破碎脱落,涂于皮肤表面后手感滑爽、无异物感;与皮肤具有良好的藕合性,使用后易去除,不污染衣物。 (6)进行了氯硝柳胺涂膜剂的质量研究。制剂具有较好的流动性和成膜性,可均匀涂布于皮肤上,所成药膜具有较好的可塑性,易于揭布。含量测定准确可行,方法简便。制剂质量稳定,无明显的皮肤刺激性。配成液体制剂后,基质质量稳定,不含可见固体成分。常温下密闭储藏,粘稠度很少变化,不发生败坏等变质现象。用乙基纤维素作为成膜材料制成的涂膜剂,符合涂膜剂所规定的质量要求和标准,可以作为一种成膜材料在某些难溶性药物的涂膜剂配制中使用。
[Abstract]:Niclosamide is a salicyloyl aniline compound, with excellent molluscicidal effect, low toxicity to human and animals, WHO is the only recommended molluscacide. But because of niclosamide low solubility and poor dispersion in water, so the suspension rate is low, limiting its full play of molluscicidal effect because of this. How to increase the solubility and suspension rate, is a key problem to improve the molluscicidal effect. Nano drug suspension is a kind of nanoparticle drug delivery system developed in recent years, it can increase the solubility of drugs and drug dissolution rate, improve the insoluble medicinal effects of drugs in addition, it has simple preparation process, high drug loading characteristics. This paper will study on Preparation of nano suspension into niclosamide, has certain reference value for the preparation of poorly soluble drugs. At the same time, to carry out the research process and quality of preparation of niclosamide film coating agent, chlorine The research and development of the external use of nitrine has created new ideas. The main research work is as follows:
(1) by high-pressure homogenization method, niclosamide nano suspension was prepared. The influences of the type and amount of wetting agent, suspending agent type and dosage, the effect of carrier type on suspension performance, and homogenization pressure, reproducibility of the effects of the number of cycles to the particle size and the method. The results show that the main factors affecting drug particle size is the homogenization pressure and cycle number: with the increase of homogenization pressure and cycle number, nano drug suspension particle size decreased, and showed good dispersion. Based on the homogenization pressure and cycle number control, can be prepared in accordance with the size requirement of niclosamide nano suspension and high pressure homogenization method has high reproducibility. In addition, the existence of surfactant, nano particles may be inhibited to a certain extent, reunion, maintaining the stability of the system.
(2) the prepared by high-pressure homogenization of niclosamide nano suspension, studied the characterization and physicochemical properties. TEM showed the spherical or nearly spherical particles. The nano suspension suspension rate is much higher than that of WP. Moreover, suspension stability, suspension time was prolonged.
(3) in order to improve the stability of niclosamide nano suspension, spray powder of niclosamide nano suspension was prepared by spray drying process was studied. The properties of niclosamide nano suspension spray prepared by high-pressure homogenization after drying, the image analysis showed that the crosslinking structure dissolved percentage. Niclosamide spray powder of niclosamide is much higher than that of TC, suspension rate is also higher than niclosamide wettable powders, the wettability is improved significantly. Moreover, the suspension stability, suspension time prolonged.
(4) the efficacy of niclosamide nano suspension was studied. Experimental results show that under the same conditions, the molluscicidal effect of niclosamide nano suspension is commercially available WP 2 times; in order to achieve the molluscicidal effect of the same dosage of nanoparticles suspension is the sale of half wet powder, greatly reducing the dosage. Moreover, with reducing the dosage of the drug, the toxic and side effects caused by decreased, but also reduce the pollution of the environment, which has a strong practical value.
(5) studied the prescription and process of niclosamide film. Preparations made without drugs are colorless and transparent, clear liquid, containing the drug coating agent for the bright yellow, transparent liquid. No precipitation between drug and membrane materials, occurrence of discoloration incompatibility phenomenon, easy to spread show, after coating with quick drying performance, can form a dry film. The film has good adhesion, uniformity and tear resistant, not easy to be broken off, coating on the skin surface smooth, no foreign body sensation; has good coupling with the skin, easy removal after use, no pollution to clothes.
(6) studied the quality of niclosamide film. The preparation has good fluidity and film-forming properties can be uniformly coated on the skin, the medicine film has good plasticity, easy to peel cloth. Content determination method is simple, accurate and feasible. The quality is stable, no obvious skin irritation. With liquid preparation, matrix quality and stability, do not contain visible solid components. Under normal temperature and airtight storage, the viscosity of little change, no corrupt phenomenon. Using ethyl cellulose as metamorphosed into membrane material coating agent, coating agent to meet the quality requirements stipulated and standard, can be used as a membrane material in some insoluble drug coating agent prepared in use.

【学位授予单位】：华中科技大学
【学位级别】：硕士
【学位授予年份】：2007
【分类号】：R184

【引证文献】