离子敏感眼用原位凝胶的制备及体内外评价-药学 药剂学专业论文.docxVIP

兰州大学硕士学位论文平均回收率为100．94％，日内日间精密度RSD均小于2．87％。该眼用原位凝胶在40 兰州大学硕士学位论文 平均回收率为100．94％，日内日间精密度RSD均小于2．87％。该眼用原位凝胶在40 ℃温度下放置10 d，含量降至标示量的95．47％，于照度为(4500-J：500)Ix下放置 10 d，含量降至标示量的96．95％；在25℃、避光条件下放置3个月，含量降至标 示量的72．04％；在4℃冰箱中放置3个月，含量降至标示量的95．1舷。 结论：(1)结冷胶能够延缓硝酸毛果芸香碱从原位凝胶中的释放，且随结 冷胶浓度的增加，缓释效果更加明显；其体内药效学评价表明，该原位凝胶滴 眼剂能显著延长药物作用时间。(2)硝酸毛果芸香碱为叔胺类化合物，由于其 本身性质不稳定，因而导致该制剂不稳定，对温度和光照均敏感，在室温和冷 藏条件下均不太稳定，而如何解决其稳定性的问题有待进一步研究。 创新性：(1)首次在国内考察了结冷胶用于眼用制剂后其对药物体外释放 度及药效学的影响。(2)首次建立了硝酸毛果芸香碱的正相高效液相色谱含量 测定方法。 关键词：结冷胶；离子敏感原位凝胶；硝酸毛果芸香碱；体外释放；药效 学；质量标准；稳定性 Ⅱ 兰州大学硕士学位论文Preparation 兰州大学硕士学位论文 Preparation of Ophthalmic Ion—sensitive in Situ Gel and its Evaluation Abstract Objective：Ophthalmic in—situ gel of Pilocarpine Nitrate(P№was prep盯ed． The release behavior in vitro and the pharmacod)7namics in rabbit were investigated and its quality standard was developed． Methods：(1)Ophthalmic in-situ gels of PN were prepared containing gellan gum at different concentration．Ion-sensitive gellan gum was used as the matrix of gel and PN was selected as a model drug．According to the first method of measuring release behavior in the second part of China Pharmacopeia(2005)，drug release was determined from in-situ gels in artificial tears，and compared with the release舶m PN eye drop．The pharmacodynamics of in-situ gels in rabbit WaS evaluated by measuring intraocular pressure(IOP)and pupillary diameter．(2)High performance liquid cllromato伊aphy was developed to determine the content of PN in in—situ gel． Analytical column was SHIM-PACK CLC-NH2(1 50 minx4 m／n，5 um)．The mobile phase consisted of methan01．The mobile phase was delivered at a flow rate of 0．8 mL ．min～．Detection was performed at wavelength of 2 1 1 nm under 40℃．And the stability of the optimal formulation was primarily studied by influential factor test， accelerated test and long-term test． Results：(1)PN was completely released from conventional eye drop within 3也 while for the PN-containing 0．4％gellan gum the amount of PN released was about Ⅲ 兰州大学硕士学位论文68％wit