【作者】 张翔；

【导师】 胡一桥；

【作者基本信息】 南京大学 ， 药剂学， 2013， 硕士

【摘要】 贝西沙星混悬型滴眼剂是FDA2009年批准上市的第一个专门针对眼部研发的第四代氟喹诺酮类抗生素。该制剂属于新型的pH敏感型凝胶,进入眼部后,随着pH值的上升能够黏度增加,形成凝胶,能够增加眼部滞留时间,提高药物眼部利用率,是一种极具前景的细菌性结膜炎治疗新药。本文对成功对贝西沙星混悬型滴眼剂进行了处方摸索、工艺放大、质量研究及稳定性研究。以渗透压及体系黏度为指标,确定了主要辅料聚卡波非、NaCl、甘露醇的用量分别为0.82%、0.45%、2.2%。利用玻璃板倾斜法对泊洛沙姆407的作用进行研究并确定其用量为0.1%。考察了灭菌前后制剂各项指标的变化,确定了高温高压的灭菌方式。在确定处方工艺后,将自制实验室样品与原研产品就外观、pH、粒径、渗透压、黏度等指标进行比较,并进行溶血及眼部滞留试验进一步验证处方,眼部时间的结果表明,自制样品的眼部滞留时间是传统滴眼剂的3倍,且与原研样品结果一致。中试放大成功生产了3批每批5千瓶的样品。对三批样品的性状、pH值、黏度、渗透压、装量、密度、沉降体积比、可见异物、粒度、含量、有关物质、对映异构体、苯扎氯铵、无菌进行了研究。三批生产样品指标均符合标准,且与原研样品无明显差别。加速试验三批样品各项指标保持稳定,且均达到限度要求。6个月长期试验后各项指标保持稳定,也能满足限度要求。稳定性研究表明,产品性质稳定,在有效期内能够保证产品的质量。贝西沙星混悬型滴眼剂处方可靠,制备方法简单,工艺重现性强,各项参数稳定与参比制剂基本一致。中试放大三批样品质量与稳定性结果均符合要求。更多还原

【Abstract】 Besivance(?) was approved by FDA in2009for conjunctivitis treatment. It is the first fluoroquinolones only for topical use. Besivance(?) is a new pH responsive hydrogel. When given into eyes, viscosity increases with an increase in pH. The residence time in eyes is prolonged and the bioavailability is improved which both make Besivance(?) a promising ophthalmic new drug.In this paper, we successfully finished formula study, quality control, pilot production and stability study of the besifloxacin ophthalmic suspension. Dosage of polycarbophil, NaCl and mannitol was determined to be0.82%,0.45%and2.2%respectively with osmotic pressure and viscosity taken as indexes. We also studied the function of poloxamer407in Besivance(?) to better decide its dosage. Autoclave sterilization was chosed since no significant change was found in every index before and after sterilization. We further compared our generics sample with Besivance(?). Residence time of our generic sample is3times as long as that of traditional eye drops. Result of Besivance(?) is the same. Three batches (5thousand bottles per batch) of besifloxacin ophthalmic suspension were produced by pilot production. Tests for appearance, pH, viscosity, osmotic pressure, content uniformity, density, sedimentation ratio, visible particles, particle size, content of besifloxacin, related substance, enantiomer, content of benzalkonium chloride, sterilization were taken to study the quality of the pilot production products. Outcomes met all the requirments and kept the same with Besivance(?). We then studied the stability of our products. Results of acceleration test and long-term test proved our besifloxacin ophthalmic suspension was stable. We successfully worked out a reliable formula of the besifloxacin ophthalmic suspension. Its production method is simple and practicable for industrial production. Our generic besifloxacin ophthalmic suspension is proved to be noninferior to Besivance(?).更多还原