凝胶骨架型碳酸锂缓释片的体外释放度及释药特性

In vitro release rate and release characteristics of gel-matrix lithium carbonate sustained-release tablets

背景:目前国内外文献报道的碳酸锂缓释片多采用海藻酸、卡波姆等制备凝胶型骨架片,同样作为水溶性骨架材料的羟丙基甲基纤维素,也可作为碳酸锂的缓释基质。目的:研制凝胶骨架型碳酸锂缓释片,进行处方筛选考察其体外释放度及释药特性。设计、时间及地点:药物制剂研究,于2008-05/12在江苏恩华药业有限公司实验室完成。材料:碳酸锂(恩华药业股份有限公司);羟丙基甲基纤维素K4、K15、K100(上海卡乐康包衣技术有限公司);乳糖(镇江康富生物工程有限公司);聚乙烯吡咯烷酮K30(上海运宏化工制剂辅料技术有限公司)。方法:以羟丙基甲基纤维素为骨架材料,按不同处方制备碳酸锂缓释片。分别考察不同羟丙基甲基纤维素的用量、黏度及片剂的硬度、片型对体外释放度的影响,通过释放度试验评价缓释效果,并初步研究其释药特性。主要观察指标:羟丙基甲基纤维素的不同黏度、不同用量、片剂的不同硬度、不同比表面积对碳酸锂缓释片释放度的影响。结果:凝胶骨架型碳酸锂缓释片的释药速度主要受羟丙基甲基纤维素黏度及用量的影响。随着片剂中羟丙基甲基纤维素黏度的增高,药物的释放速度变慢。含骨架材料为30%HPMCK15为优化的理想处方。以不同的压片压力制备的硬度为4～9kg/cm2缓释片的释放曲线重叠,其释放速率几乎无差别。随着片剂的比表面积的增加,药物释放度略有加快。选择键型冲头压片,即可达到标准要求,其释放规律符合Higuchi方程。结论:选择合适的羟丙基甲基纤维素的黏度和用量,采用键型冲头压片,使片子硬度控制在4～9kg/cm2,制备水溶性凝胶骨架型碳酸锂缓释片,体外试验具有明显的缓释效果,其释药为扩散与溶蚀并存的过程。

BACKGROUND： Based on documents abroad and home, both alginic acid and carbomer are used to prepare gel matrix of lithium carbonate tablets; furthermore, hydroxypropyl methyl cellulose （HPMC）, a kind of water-soluble skeletal material, can be used as controlled release matrix of lithium carbonate tablets. OBJECTIVE： To prepare gel-matrix lithium carbonate sustained-release tablets, and to investigate the in vitro release rate and release characteristics. DESIGN, TIME AND SETTING： A pharmaceutical preparation study was performed at Laboratory of Jiangsu Nhwa Pharmaceutical Co., Ltd., from May to December 2008. MATERIALS： Lithium carbonate was provided by Jiangsu Nhwa Pharmaceutical Co., Ltd.; hydroxypropyl methyl cellulose （HPMC） K4, K15, and K100 were provided by Shanghai Colorcon Coating Technology Co., Ltd.; lactose was provided by Zhenjiang Kangfu Bioengineering Co., Ltd.; polyethylene pyrrolidone PVPK30 was provided by Shanghai Yunhong Pharmaceutical Excipients ＆ Technology Co., Ltd. METHODS： HPMC was used as the matrix material to prepare lithium carbonate sustained-release tablets according to various prescriptions. The effects of HPMC amount, viscosity, hardness, and types on in vitro release rate were studied respectively so as to evaluate controlled-release effect and analyze release characteristics initially. MAIN OUTCOME MEASURES： Effects of HPMC amount, viscosity, hardness, specific surface area on release rate of lithium carbonate sustained-release tablets. RESULTS： Drug-release velocity of gel-matrix lithium carbonate sustained-release tablets was mainly affected by HPMC amount and viscosity. The increased viscosity of HPMC might slow down the release velocity of drugs. Matrix material containing 30% HPMCK15 was an ideal prescription. Sustained-release tables with the hardness of 4-9 kg/cm2 under various pressures had overlapped release curves, thus their release velocities were not significantly different. The increased specific surface area of tables might speed up the release velocity of drugs. The bond-punch tablet might meet the standard requirements, and the release laws were in coincidence with Higuchi equation. CONCLUSION： Gel-matrix lithium carbonate sustained-release tablets which meat appropriate viscosity and amount of HPMC, bond-type punch, and hardness 4-9 kg/cm2 had a remarkable in vitro sustained-release effect. Furthermore, the drug release was a coexistent process of diffusion and dissolution.