伏立诺他胶囊的制备及其稳定性考察  

Investigation of the Preparation and Stability of Vorinostat Capsule

作　　者：陈钦伟[1] 归小龙[1] 安富荣[1] 崔岚[1] 王勤[1] 

机构地区：[1]上海交通大学医学院附属仁济医院药剂科,上海200001

出　　处：《中国药房》2013年第33期3126-3128,共3页China Pharmacy

摘　　要：目的:制备伏立诺他胶囊并考察其稳定性。方法:用研磨法制备伏立诺他微粉,测定其粒径,并以差示扫描量热仪(DSC)和粉末X射线衍射(XRD)法检测晶型的变化,测定研磨前后堆密度和休止角以考察微粉的流动性。将伏立诺他微粉与微晶纤维素、羧甲基淀粉钠、硬脂酸镁混合后直接填充制备成伏立诺他胶囊。采用高效液相色谱法测定主药含量、有关物质和60min内的累积溶出度。考察高温(60℃)、高湿(相对湿度92%)和强光(4500lx)条件下放置10d的稳定性。结果:研磨后伏立诺他的粒径从11μm减小到3μm;126℃的吸热峰消失,晶型改变;堆密度从0.24g/ml增加到0.31g/ml;休止角从40°减小到36°;每粒胶囊平均装量为215mg,每粒胶囊装量偏差RSD=3.96%(n=20);含量为(100.17±1.48)%,有关物质为(0.41±0.08)%,60min内的累积溶出度约为90%,在高温、高湿、强光下各检测指标变化不大。结论:研磨法成功制备了伏立诺他胶囊,其稳定性良好。OBJECTIVE： To prepare Vorinostat capsules and to investigate its stability. METHODS： Vorinostat micropowder was prepared with grinding. The particle size of micropowder was determined. The crystal forms were tested by DSC and XRD. Bulk density and angle of repose of micropowder were tested to investigate the flowability of micropowder. The vorinostat micro- powder, microcrystalline cellulose, sodium carboxymethyl starch and magnesium stearate were mixed and filled into capsules. The contents of main component, related substance and accumulative dissolution within 60 min were determined by HPLC. The stability of the product was investigated in some intensive conditions such as temperature of 60 ~C, relative humidity of 92% and light of 4500 Ix for 10 days, respectively. RESULTS： After grinding, the particle size of vorinostat decreased from 11 pm to 3 I.tm; endo- thermie peak disappeared at 126 ~C, and crystal form changed; bulk density increased from 0.24 g/ml to 0.31 g/ml and angle of re- pose decreased from 40~ to 36~; average amount of each capsule was 215 mg, and RSD of amount deviation of each capsule was 3.96% （n=20） ; the content of capsule was （100.17±1.48）%, and relevant substance was （0.41 ± 0.08）%; accumulative dissolu- tion was 90% within 60 min, and the index had no significant change under high temperature, high moisture and high light. CON- CLUSIONS： Vorinostat capsule has been prepared by grinding successfully with good stability.

关 键 词：制备 伏立诺他 胶囊 稳定性 研磨 溶出度 

分 类 号：R944[医药卫生—药剂学]