摘要
目的:本研究利用扫描电子显微镜(scanning electron microscope, SEM)对瑞益宁■的超微结构进行观察分析,探讨该方法对渗透泵制剂类仿制药研发的适用性。方法:通过干法制粒、粉末直压及湿法制粒制备自研制剂,利用SEM观察参比制剂和自研制剂的超微形态,采用MATLAB图像处理程序计算制剂颗粒的长轴值、结合方式和面孔隙度,利用SEM成像结果对原料药的粒径分布和释药孔径进行分析。通过体外溶出实验比较自研制剂与参比制剂的药物释放特性。结果:干法制粒所得颗粒呈齿状结合、表面扁平且颗粒间空隙小。粉末直压制备的颗粒呈齿状结合、形态不一且颗粒间空隙大。湿法制粒研制的颗粒形态多不规则,部分颗粒可形成成片的固体桥,颗粒间空隙极小。与参比制剂的SEM成像结果对比,可推断出瑞益宁■为干法制粒工艺。瑞益宁■ SEM成像分析发现,其原料粒径分布范围为0.25~7.75μm,D50为(2.91±1.60)μm。释药孔分析结果显示激光致孔的参比制剂孔形状为锥形,且有熔融层,孔径为(503.4±6.19)μm,孔深度为(583.8±6.83)μm,深径比为(1.2±0.016),锥度为23.2°。体外溶出结果表明,干法制粒工艺的片剂与参比制剂的释放行为基本一致,16 h即可实现完全释放。结论:SEM可实现渗透泵制剂超微结构的表征解析,可为渗透泵制剂的研发提供技术支持。
Objective:To observe and analyze the ultrastructure of glipizide extended release tablets by scanning electron microscope(SEM), and explore the potential application of SEM in developing generic osmotic pump drugs. Methods:The self-developed agents were fabricated using dry granulation, powder direct pressing and wet granulation, respectively. SEM was used to observe the ultrafine morphology of the reference agent and the self-developed agents. The MATLAB image processing program was applied to measure the long axis value, the combination mode and the surface porosity of granules. The particle size distribution and released pore size of the drug substance were identified based on SEM imaging results. In vitro dissolution test was carried out to compare the release features of the self-developed agents and the reference agent. Results:The particles obtained by dry granulation exhibited a flat surface with dentate bonds as well as small interparticle voids. The particles made by powder direct pressing had different shapes with dentate bonds and large interparticle voids. The morphology of particles developed by wet granulation was irregular, and some of them formed a solid bridge, with interparticle voids much smaller than those of the other particles. By comparing the SEM imaging results, it could be inferred that the original glipizide controlled-release tablets were synthesized by dry granulation process. The SEM imaging analysis revealed that the particle size distribution of the reference tablets material was 0.25~7.75 μm, with an average value of(2.91±1.60) μm. The drug release pore analysis showed that the laser-induced pores of the reference drug was tapered and had a molten layer with a pore diameter of(503.4±6.19) μm and a pore depth of(583.8±6.83) μm. The depth-to-diameter ratio and taper were(1.2±0.016) and 23.2°, respectively. The in vitro dissolution test demonstrated that the release manner of dry granulation process-made agent was the same as that of the reference agent. Both of them releas
作者
陈娟娟
苏峰
杜冬生
CHEN Juan-juan;SU Feng;DU Dong-sheng(Hefei Industral Pharmaceutical Institute Co.,Ltd.,Hefei 230088,China;Shenyang Pharmaceutical University,Shenyang 110016,China;Anhui Normal University,Wuhu 241000,China)
出处
《中国新药杂志》
CAS
CSCD
北大核心
2020年第6期701-709,共9页
Chinese Journal of New Drugs
关键词
扫描电镜
渗透泵制剂
表征
scanning electron microscope
osmotic pump drugs
characterization
