Sanganwar Ganesh P, Gupta Ram B
Department of Chemical Engineering, Auburn University, Auburn, AL 36849, USA.
Int J Pharm. 2008 Aug 6;360(1-2):213-8. doi: 10.1016/j.ijpharm.2008.04.041. Epub 2008 May 4.
Dissolution rate of a poorly water-soluble drug, fenofibrate, is increased by adsorbing the drug onto silica. The adsorption is achieved by first dissolving the drug in supercritical carbon dioxide and then depressurizing the solution onto silica. Loadings of up to 27.5 wt.% drug onto silica are obtained. Since solvents are not used in the loading process, the fenofibrate/silica formulation is free of any residual solvent, and carbon dioxide is freely removed upon depressurization. The formulation is characterized using infrared spectroscopy, ultraviolet spectroscopy, X-ray diffraction, differential scanning calorimetry and scanning electron microscopy. Based on in vitro dissolution study, a significant increase in the dissolution rate (approximately 80% drug release in 20 min) of drug-silica formulation is observed as compared to micronized fenofibrate (approximately 20% drug release in 20 min), which can be attributed to increase in the surface area and decrease in the crystallinity of drug after adsorption onto silica. Two different formulations are compared: (A) amorphous fenofibrate/silica and (B) slightly crystalline fenofibrate/silica. The second formulation is found to be more stable on storage.
通过将难溶性药物非诺贝特吸附到二氧化硅上，可提高其溶出速率。吸附过程是先将药物溶解在超临界二氧化碳中，然后将溶液降压到二氧化硅上实现的。药物在二氧化硅上的负载量可达27.5 wt.%。由于负载过程中不使用溶剂，非诺贝特/二氧化硅制剂不含任何残留溶剂，降压时二氧化碳可自由除去。该制剂采用红外光谱、紫外光谱、X射线衍射、差示扫描量热法和扫描电子显微镜进行表征。基于体外溶出研究，与微粉化非诺贝特（20分钟内约20%药物释放）相比，药物-二氧化硅制剂的溶出速率显著提高（20分钟内约80%药物释放），这可归因于药物吸附到二氧化硅后表面积增加和结晶度降低。比较了两种不同的制剂：（A）无定形非诺贝特/二氧化硅和（B）微结晶非诺贝特/二氧化硅。发现第二种制剂在储存时更稳定。
