Wu Ke, Li Jing, Wang Wayne, Winstead Denita A
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA.
J Pharm Sci. 2009 Jul;98(7):2422-31. doi: 10.1002/jps.21598.
Solid dispersions of a poorly water-soluble drug piroxicam in polyvinylpyrrolidone (PVP) were prepared by precipitation with compressed antisolvent (PCA) and spray drying techniques. Physicochemical properties of the products and drug-polymer interactions were characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, and differential scanning calorimetry, etc. Piroxicam was found amorphously dispersed in both solid dispersion systems with the drug to polymer weight ratio of 1:4. Spectra data indicated the formation of hydrogen bonding between the drug and the polymer. Both techniques evaluated in this work resulted in improved dissolution of piroxicam. By comparison, PCA-processed solid dispersions showed distinctly superior performance in that piroxicam dissolved completely within the first 5 min and the dissolution rate was at least 20 times faster than raw drug did within the first 15 min. PCA processing could provide an effective pharmaceutical formulation technology to improve the bioavailability of poorly water-soluble drug.
采用压缩反溶剂沉淀法(PCA)和喷雾干燥技术制备了难溶性药物吡罗昔康在聚乙烯吡咯烷酮(PVP)中的固体分散体。通过粉末X射线衍射、傅里叶变换红外光谱和差示扫描量热法等对产物的物理化学性质及药物-聚合物相互作用进行了表征。发现吡罗昔康以无定形形式分散在药物与聚合物重量比为1:4的两种固体分散体系中。光谱数据表明药物与聚合物之间形成了氢键。这项工作中评估的两种技术均使吡罗昔康的溶出度得到了提高。相比之下,PCA处理的固体分散体表现出明显更优异的性能,吡罗昔康在前5分钟内完全溶解,且在最初15分钟内的溶出速率比原料药至少快20倍。PCA处理可为提高难溶性药物的生物利用度提供一种有效的药物制剂技术。