School of Pharmacy, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
Int J Pharm. 2013 Oct 15;455(1-2):267-75. doi: 10.1016/j.ijpharm.2013.07.021. Epub 2013 Jul 20.
The majority of the candidate drug entities exhibit solubility-limiting absorption. Nanocrystal suspensions with particle size in the nanometer scale (nanonization) can increase aqueous solubility and improve oral bioavailability. Regarding the importance of nanosuspension solidification, this study intended to study the critical parameters on redispersed particle size of dried nanocrystals as pretabletting material during spray drying process, such as supporting agents, inlet temperature and feed rate. Fenofibrate with poor water solubility and low melting point was used as a model drug. Nanocrystals of fenofibrate were prepared by a bead-milling method. Five types of hydrophilic excipients in combination with sodium dodecyl sulfate (SDS) were studied as supporting agents during spray drying. The resultant products were characterized by particle size analysis, scanning electron microscopy imaging, differential scanning calorimetry, X-ray powder diffraction and dissolution testing. Spray dried powder with a mean redispersed particle size of 699 nm was produced by using mannitol and SDS as supporting agent. Weight ratio (RF/m) of fenofibrate:mannitol and inlet temperature strongly influenced the particle size of the nanocrystals. The optimal inlet temperature and feed rate was optimized as 75 °C and 4 mL min(-1), respectively. Partially transformation of fenofibrate crystalline to the amorphous form was observed. The dissolution profiles of tablets prepared with the spray dried powder were similar to the commercial nanocrystal formulation Lipidil™ ez, and faster than that of the micronized formulation. The relative bioavailability of the spray-dried formulation was determined to be 89.6% taking Lipidil™ ez as the reference. There were no significant statistic differences of AUC0-72 and Cmax between the two formulations.
大多数候选药物实体表现出溶解度限制的吸收。粒径在纳米级的纳米晶体混悬剂（纳米化）可以增加水溶解度并提高口服生物利用度。关于纳米混悬剂固化的重要性，本研究旨在研究喷雾干燥过程中作为预压片材料的干燥纳米晶体再分散颗粒粒径的关键参数，如辅料、进口温度和进料速度。具有低水溶性和低熔点的非诺贝特被用作模型药物。通过珠磨法制备非诺贝特纳米晶体。研究了五种亲水辅料与十二烷基硫酸钠（SDS）联合作为喷雾干燥时的辅料。通过粒径分析、扫描电子显微镜成像、差示扫描量热法、X 射线粉末衍射和溶解试验对所得产物进行了表征。使用甘露醇和 SDS 作为辅料，喷雾干燥粉末的平均再分散粒径为 699nm。非诺贝特：甘露醇的重量比（RF/m）和进口温度强烈影响纳米晶体的粒径。优化的进口温度和进料速度分别为 75°C 和 4mL/min。观察到非诺贝特晶型部分转化为无定形形式。用喷雾干燥粉末制备的片剂的溶出曲线与商业纳米晶体制剂 Lipidil™ ez 相似，且快于微粉化制剂。以 Lipidil™ ez 为参比，喷雾干燥制剂的相对生物利用度为 89.6%。两种制剂的 AUC0-72 和 Cmax 无统计学差异。
