Makar Rana Refaat, Latif Randa, Hosni Ehab Ahmed, El Gazayerly Omaima Naim
Faculty of Pharmacy, Ahram Canadian University, Egypt.
Faculty of Pharmacy, Department of Pharmaceutics, Cairo University, Cairo, Egypt.
Adv Pharm Bull. 2017 Dec;7(4):557-567. doi: 10.15171/apb.2017.067. Epub 2017 Dec 31.
Triple solid dispersion adsorbates (TSDads) and spherical agglomerates (SA) present new techniques that extensively enhance dissolution of poorly soluble drugs. The aim of the present study is to hasten the onset of hypoglycemic effect of glimepiride through enhancing its rate of release from tablet formulation prepared from either technique. Drug release from TSDads or SA tablets with different added excipients was explored. Scanning electron microscopy (SEM) and effect of compression on dissolution were illustrated. Pharmacodynamic evaluation was performed on optimized tablets. TSDads & SA tablets with Cross Povidone showed least disintegration times of 1.48 and 0.5 min. respectively. Kinetics of drug release recorded least half-lives (54.13 and 59.83min for both techniques respectively). Cross section in tablets displayed an organized interconnected matrix under SEM, accounting for the rapid access of dissolution media to the tablet core. Components of tablets filled into capsules showed a similar release profile to that of tablets after compression as indicated by similarity factor. The onset time of maximum reduction in blood glucose in male albino rabbits was hastened to 2h instead of 3h for commercial tablets. After optimization of tablet excipients that interacted differently with respect to their effect on drug release, we could conclude that both amorphisation and spheronization were equally successful in promoting in vitro dissolution enhancement as well as providing a more rapid onset time for drug action in vivo.
三元固体分散吸附物（TSDads）和球形附聚物（SA）呈现出可广泛提高难溶性药物溶出度的新技术。本研究的目的是通过提高格列美脲从采用这两种技术制备的片剂中的释放速率，来加速其降血糖作用的起效时间。研究了添加不同辅料的TSDads或SA片剂的药物释放情况。阐述了扫描电子显微镜（SEM）以及压片对溶出度的影响。对优化后的片剂进行了药效学评价。含交联聚维酮的TSDads和SA片剂的崩解时间最短，分别为1.48分钟和0.5分钟。药物释放动力学记录的半衰期最短（两种技术分别为54.13分钟和59.83分钟）。片剂的横截面在SEM下显示出有组织的相互连接的基质，这解释了溶出介质能够快速进入片剂核心。填充到胶囊中的片剂成分显示出与压片后片剂相似的释放曲线，相似因子表明了这一点。雄性白化兔血糖最大降幅的起效时间从市售片剂的3小时加快到了2小时。在优化了对药物释放有不同相互作用的片剂辅料后，我们可以得出结论，非晶化和球化在促进体外溶出度提高以及为体内药物作用提供更快起效时间方面同样成功。
