【作者】 胡瑞标；

【导师】 程怡；

【作者基本信息】 广州中医药大学 ， 药剂学， 2011， 硕士

【摘要】 头孢克洛属第二代口服头孢类抗生素,具有抗菌谱广、高效、口服吸收良好、组织分布广、不良反应轻微等突出优点,为当前临床上治疗呼吸道、泌尿道、皮肤及软组织等感染性疾病较理想、较可靠的一线抗生素药物。本文将头孢克洛制成粉末状的干混悬剂。具体研究内容有：头孢克洛干混悬剂的处方与工艺研究,头孢克洛干混悬剂的液体物态特征研究,头孢克洛干混悬剂的溶出行为比较,头孢克洛干混悬剂的质量研究和稳定性研究。本文以沉降体积比、再分散性、酸度为评价指标初步筛选头孢克洛干混悬剂的处方工艺,并通过测定混悬液中微粒的粒径,Zeta电位,粘度曲线评价处方工艺的合理性。确定了头孢克洛干混悬剂的处方为：100g的头孢克洛干混悬剂(50包,2g／包)含头孢克洛6.25g, HPMC(K425)4.0g,微粉硅胶0.50g,橘子香精1.0g,日落黄0.025g,糖粉88.2g。制备工艺如下：(1)取干燥的头孢克洛原料药粉碎,过150目筛,备用。(2)取干燥的HPMC(K425)、糖粉、橘子香精过100目筛,备用。(3)以等量递增法,按处方量依次将(1)、(2)项下及日落黄、微粉硅胶混匀,最后与糖粉等量递增混匀,即得。(4)以上操作环境相对湿度应小于75%。原辅料相容性实验表明：在相容性试验各条件下,原料药、原辅料混粉的头孢克洛含量、有关物质均无发生显著变化,且原辅料混粉变化趋势与原料一致,表明辅料对头孢克洛的稳定性和质量没有明显影响。头孢克洛干混悬剂的液体物态特征研究表明,受试制剂的粒径范围在0.7～1.5μm之间。粒径分布均匀,呈正态分布,物理稳定性较高,用旋转粘度计测定其黏度,对其剪切速度随剪切应力的变化作图可得,该制剂的流动曲线符合假塑性流动的特点。假塑性流体的混悬剂在静置状态下黏度较大,而在倾倒时黏度较小,既有利于混悬剂的稳定,又不影响倾倒。对参比制剂和受试制剂的ζ电位进行测定,结果表明参比制剂1和受试制剂所配混悬液ζ电位绝对值的平均值分别为16.36 mVT和19.67mV,呈絮凝状态。对参比制剂和受试制剂的沉降体积比和再分散性进行考察,得出参比制剂1与受试制剂的沉降体积比为1,再分散性好。本文参考中国药典2010版规定的头孢克洛干混悬剂溶出方法,分别考察粉末状头孢克洛干混悬剂和颗粒状头孢克洛干混悬剂在纯水、pHl.2人工胃液、pH5.5与pH6.8磷酸盐缓冲液四种溶出介质中的体外溶出行为,以高效液相色谱法进行测定,并采用f2相似因子法评价受试制剂和市售参比制剂溶出曲线的相似度。结果表明,在四种溶出介质下,受试制剂与参比制剂的相似因子分别为66.81,58.25,60.19和68.19。两种性状不同的头孢克洛干混悬剂的溶出曲线相似,初步提示该受试制处方、工艺合理。在受试制剂的质量研究中,本文选择两个不同厂家、不同性状的头孢克洛干混悬剂为参比制剂。质量研究结果表明：受试制剂与参比制剂质量相当,均符合《中国药典》2010版要求。在受试制剂的稳定性研究中,本文进行了影响因素试验、加速试验和长期实验。实验结果表明,受试制剂在高温60℃、高湿、强光的条件下放置10天,外观、酸度、溶出度、沉降体积比及含量均无明显变化,有关物质略有增加,但仍在限度范围内,说明本品对高温、高湿、强光基本稳定。受试制剂在加速试验6个月,有关物质略有增加,但仍在限度范围内；外观、酸度、溶出度、沉降体积比及含量均无明显变化,说明本品的有效期可暂定为2年。长期试验6个月,各项指标仍符合规定,长期稳定性考察继续进行。更多还原

【Abstract】 Cefaclor is a second-generation oral cephalosporin, which is a broad spectrum antibiotic. Cefaclor is effective, good oral absorption, wide tissue distribution and it s adverse reactions are mild. Cefaclor is the first-line antibiotics which is use for the treatment of clinical respiratory, urinary tract, skin and soft tissue infections.This paper studied on the formula and preparation of Cefaclor dry powders for oral suspension, the really research contents were the studies on the quality, the stability and characteristics of liquid suspension made from different components, furthermore, studied on the similarity of dissolution profiles of Cefaclor for Suspension between two different shapes,According to the acidity, the ratio of subsided volume and the re-dispersion time, the prescription and technique of Cefaclor for Suspension have been found. Using the particle size, Zeta potention, viscosity curves as index, the preliminary study of the prescription and technique of Cefaclor for suspension indicated that the best prescription is Cefaclor 6.25g, HPMC(K425) 4. 00g, Silica Powder 0.05g, Orange Flavor 1.00g, Sunset Yellow 0.025g, Sucrose Powder 88.2g, which is made a total of 100g. The preparation of this Cefaclor for Suspension is to crushed dry cefaclor, pass through a 150-mesh,crushed dry HPMC(K425), Orange Flavor and Sucrose Powde, pass through a 100-mesh, mix all ingredients, prepared in less than 75% relative humidity.Materials compatibility test showed that the content and related substances of Cefaclor had no significant change under various conditions. the materials had no significant effect on the quality and stability of CefaclorOn study of the characteristics of the liquid suspension made from different components,the particle size, Zeta potention, viscosity curves had been determinated. The range of the particle size in the liquid suspension is between 0.7～1.5μm. The particle size distribution is very uniform, the liquid suspension exhibited high physical stability,its hydrodynamics behavior is similar to shear thinning liquid, its Zeta potention is 16.36mV, while the Zeta potention of the reference formulation is 19.67mV, the ratio of subsided volume of two products was 1 and the re-dispersion time of two products met the requirementsTo determine the dissolution percentage by authorized methods from ChP 2010, the methods were authenticated in different mediums introduced, and the similary of dissolution curve was evaluated by f2 factor. Compared with the Reference Product, the similarity factors of the dissolution curve from manufacturers were 66.81,58.25,60.19 and 68.19 in mediums of water, pH 1.2 artificial gastric juice, pH5.5 phosphate buffer solution and pH6.8 phosphate buffer solution respectively. The dissolution of characteristics of Cefaclor dry powders for oral suspension was similar to the reference product.Comparing Cefaclor dry powders for oral suspension with the reference preparations form different manufacturers The test experiment showed that its quality was similar to the reference preparations, which were eligible according to ChP 2010,During the stability analysis, the experiment of influence factors, the accelerated and long-term tests was carried out. Cefaclor dry powders for oral suspension has been put in 60℃, relative humidity of 75%, illuminated at 4500Lx respectively for 5d and 10d. Experimental result indicated that the appearance, acidity, dissolution, the ratio of subsided volume and the relative substance and content were in line with quality requirements of pharmacopoeia. In the 6 months’accelerated and long-term tests, there were no significant difference in samples.The long-term tests is still going on更多还原