藻酸双酯钠缓释片的制备及体外释放特性研究  

Preparation of propylene glycol alginate sodium sulfate sustained-release tablets and evaluation of its drug release in vitro

作　　者：王一行[1] 赵峡[1] 吴健[1] 郑传博 于广利[1] 

机构地区：[1]中国海洋大学海洋药物教育部重点实验室,山东省糖科学与糖工程重点实验室,医药学院,山东青岛266003

出　　处：《中国海洋药物》2014年第6期59-64,共6页Chinese Journal of Marine Drugs

基　　金：国家"十二五"科技支撑计划(2013BAB01B02);青岛市自主创新重大专项(13-7-1-zdzx1-hy)资助

摘　　要：目的制备藻酸双酯钠（PSS）的缓释片;建立PSS缓释片体外药物释放度的测定方法,并对其体外释放特性进行考察。方法以羟丙基甲基纤维素（HPMC）、羧甲基纤维素钠（CMC-Na）和十八醇为骨架材料,采用熔融制粒法制备PSS缓释片,并采用正交设计优化PSS缓释片的处方;采用高效液相色谱法测定PSS缓释片的体外释放度。结果建立了测定PSS缓释片药物释放度的柱前衍生高效液相色谱法,在0.3～12mg·mL-1浓度范围内与峰面积呈现良好的线性关系（R2=0.9983）,各辅料不影响PSS的含量测定。在低,中,高3个浓度下的加样回收率分别为101.97%,98.84%,101.84%,平均RSD为1.75%（n=6）,精密度RSD为1.4%（n=5）,重复性RSD为3.4%（n=5）,24h内稳定性良好,RSD为1.92%。采用正交设计确定了制备PSS缓释片的最优处方为：HPMC、CMC-Na和十八醇的用量分别为片重的15%,10%和10%,在最适条件下制备的PSS缓释片在2、6、12h内可分别释放药物30.3%,70.9%和95.5%,体外药物释放行为符合一级模型,ln（1-Q）=-0.2756t＋4.8141,r=0.9888。结论建立的柱前衍生高效液相色谱法具有专属性强,精密度和重现性好的特点,可用于PSS缓释片体外释放度的测定。采用熔融制粒法制备的PSS缓释片体外释放特性良好。Objective To prepare PSS sustained-release tablets and establish a chromatography method for release rate determination, and evaluate its release characteristics in vitro. Methods PSS sustained-re- lease tablets were prepared by melting granulation method using HPMC, CMC-Na and octadecanol as matrix materials. The release rate of PSS sustained-release tablets in vitro was determined by a precolumn derivatization high performance liquid chromatography （PC-HPLC） method, and the prescription was optimized by an orthogonal design. ResuLts A PC-HPLC method was successfully established to determine the release rate of PSS sustained-release tablets in vitro. There was a good linear relationship between peak area ratio and concentration in the range of 0. 3N 12 mg/mL （R2 =0. 9983）. All excipi- ents did not disturb the determination of release rate o{ PSS. The sample recovery rates at low,medium and high concentrations were 101. 97%, 98. 84%, 101. 84M, respectively, with an average RSD of 1.75%（n=6）. The RSD of precision test was 1. 4% （n= 5）, and the RSD of repeatability test was 3.4%（n=5）. The RSD of stability test within 24h was 1.92%. The optimum prescription was deter- mined by orthogonal design as follows： the weight percents of HPMC, CMC-Na, and octadecanol were 15%, 10%, 10%, respectively. The release rates of PSS sustained-release tablets were 30. 3%, 70. 9% and 95.5% within 2h,6h, 12h, respectively. The release characteristics of PSS were conformed to the first-order kinetics equation of Eln（1-Q）=-0. 2756t＋4. 8141, r=0. 98881. Conclusion The PC-HPLC method is suitable to determine the release rate of PSS sustained-release tablets in vitro with good spe- cificity precision and reproducibility. The release characteristics of PSS sustained-release tablets in vitro are satisfactory.

关 键 词：藻酸双酯钠 缓释片 制备 柱前衍生高效液相色谱 释放度 

分 类 号：R944[医药卫生—药剂学]