克林霉素磷酸酯聚氨酯水凝胶栓剂的制备及体外释放  

Preparation and In Vitro Release of Polyurethane Hydrogel-based Clindamycin Phosphate Vaginal Pessary

作　　者：赵万利[1] 包全英[1] 赵泽恺[1] 张灿[1] 

机构地区：[1]中国药科大学新药研究中心,江苏南京210009

出　　处：《药学进展》2012年第11期501-507,共7页Progress in Pharmaceutical Sciences

基　　金：教育部博士点基金(No.20090096110005);江苏省研究生科研创新计划(No.CX10B-375Z)

摘　　要：目的:制备一种基于聚氨酯水凝胶的克林霉素磷酸酯缓释栓剂,并考察栓剂的体外释放及其影响因素。方法:以聚乙二醇6000、二环己基甲烷二异氰酸酯及1,2,6-己三醇为原料,采用一步法合成聚氨酯水凝胶材料,并通过傅里叶变换红外光谱及溶胀率对其进行初步表征。将聚氨酯水凝胶制成特定形状的空白栓剂,载入克林霉素磷酸酯后考察所得载药栓剂的体外释放行为,并探讨聚氨酯的化学组成、栓剂厚度、栓剂载药量及释放介质pH对载药栓剂体外释放的影响。通过Ritger-Peppas方程对释放数据进行拟合,探讨栓剂的释放机制。结果:合成了4批不同化学组成的聚氨酯水凝胶材料,其结构经FTIR确证,溶胀率则随交联率的增加而逐渐降低。制备的栓剂中克林霉素磷酸酯占目标载药量的103.0%(RSD=1.8%,n=10)。体外释放结果显示聚氨酯的化学组成及栓剂载药量对释放基本无影响;释放介质pH的升高及栓剂厚度的增加会减缓药物释放。释放数据分析结果表明克林霉素磷酸酯的释放由溶胀及扩散双重机制控制。结论:基于聚氨酯水凝胶的克林霉素磷酸酯栓剂制备方法简单、可控,体外释放完全,具有良好的应用前景。Objective： To develop a polyurethane hydrogel-based and to investigate its in vitro release characteristics. Methods： clindamycin phosphate vaginal pessary, By using PEG6000, methylene-b/s （ 4- cyclohexyl isocyanate） and 1, 2, 6-hexanetriol as raw materials, a polyurethane hydrogel was synthesized by one-step method. Fourier Transform Infrared Spectroscopy （FTIR） and swelling ratio studies were performed to characterize the polyurethane. The polyurethane materials were cut into pessaries with particular geometric shape which were then loaded with clindamycin phosphate. The in vitro release characteristics of clindamycin phosphate and the influences of chemical composition of polyurethane, thickness of pessary, drug amount in the pessary and pH of release medium on them were investigated. The release data werefitted by using the Ritger-Peppas equation to investigate the release mechanism. Results： Four polyurethanes were synthesized and characterized by FTIR. The swelling ratio of the polyurethanes decreased with the increasing of the erosslink ratio. The mean clindamycin phosphate content in the pessaries accounted for 103.0% of target loading （ RSD = 1.8%, n = 10）. It was demonstrated that chemical composition of polyurethane and drug amount in the pessary had no influences on release. However, with the increase of pessary thickness and pH of release medium, drug release was slowed. Analysis of release data showed that drug release was diffusion and swelling-controlled. Conclusion： The polyurethane hydrogel was a promising matrix for vaginal delivery of clindamycin phosphate, the preparation of the vaginal pessary is simple and controllable, and the in vitro release of clindamycin phosphate is also comolete.

关 键 词：聚氨酯 水凝胶 克林霉素磷酸酯 阴道栓剂 体外释放 

分 类 号：R944.23[医药卫生—药剂学] R978.1[医药卫生—药学]