Jain Rajeev A, Brito Luis, Straub Julie A, Tessier Todd, Bernstein Howard
Acusphere, Inc, Formulation Support and Pharmaceutics, 500 Arsenal Street, Watertown, MA 02472, USA.
Eur J Pharm Biopharm. 2008 Jun;69(2):727-34. doi: 10.1016/j.ejpb.2007.12.006. Epub 2008 Jan 28.
In this study, the effect of the order in which powder blending and jet-milling were performed for the production of the bulk powders on the performance of 200-mg dose orally disintegrating tablets (ODTs) of fenofibrate was evaluated. Bulk powders composed of fenofibrate, mannitol, copovidone S630, and docusate sodium in a 10:10:2:1.2 ratio were prepared by the following three processes: process A: fenofibrate+excipients-->blending; process B: fenofibrate-->jet-milling-->blending with excipients; process C: fenofibrate+excipients-->blending-->jet-milling. The bulk powders were granulated followed by blending and tableting. The materials were tested for Differential Scanning Calorimetry (DSC), drug particle sizing post-reconstitution, dissolution, optical micrography, Scanning Electron Microscopy (SEM), Energy Dispersive X-ray Spectroscopy (EDS) and disintegration of the ODTs. It was found that the crystallinity of fenofibrate was not impacted by the blending and jet-milling processes. Process A produced materials having poorer fenofibrate reconstitution as compared to processes involving jet-milling. It was discovered that milling a blend of fenofibrate/excipient (process C) was advantageous over milling the raw drug alone (process B). Process C yielded bulk powder that showed rapid dissolution and ODTs which exhibited rapid disintegration.
在本研究中，评估了用于生产散装粉末的粉末混合和喷射研磨顺序对非诺贝特200毫克剂量口腔崩解片（ODT）性能的影响。按10:10:2:1.2的比例由非诺贝特、甘露醇、共聚维酮S630和十二烷基硫酸钠组成的散装粉末通过以下三种工艺制备：工艺A：非诺贝特+辅料→混合；工艺B：非诺贝特→喷射研磨→与辅料混合；工艺C：非诺贝特+辅料→混合→喷射研磨。将散装粉末制粒，然后混合并压片。对材料进行差示扫描量热法（DSC）、复溶后药物粒度测定、溶出度、光学显微镜检查、扫描电子显微镜（SEM）、能量色散X射线光谱（EDS）以及ODT的崩解测试。发现非诺贝特的结晶度不受混合和喷射研磨工艺的影响。与涉及喷射研磨的工艺相比，工艺A生产的材料中非诺贝特的复溶效果较差。发现研磨非诺贝特/辅料混合物（工艺C）比单独研磨原料药（工艺B）更具优势。工艺C产生的散装粉末显示出快速溶出度，并且ODT表现出快速崩解。
