超临界反溶剂流化包衣技术制备他达拉非微丸

Preparation of Tadalafil Pellets by Supercritical Antisolvent Fluidized Bed Coating Technology

本研究采用超临界反溶剂流化(SAS-FB)包衣技术,将难溶性药物他达拉非包覆在微晶纤维素(MCC)微丸表面制备速释微丸,并与超临界反溶剂(SAS)法和流化床(FB)法所得制品进行表面形态和体外溶出度的对比。SAS-FB法制得微丸的扫描电镜照片显示,他达拉非以针状结晶均匀地包裹在MCC微丸表面,而FB法制得微丸中他达拉非则以块状结晶包覆在MCC微丸表面,SAS法制备的他达拉非外观形态与原料药相似,以细条状互相聚集在一起。与其他2种方法所得制品相比,SAS-FB法制备的微丸药物溶出速度更快、程度更高。通过加入表面活性剂十二烷基硫酸钠或聚乙烯吡咯烷酮对MCC微丸进行表面改性,可进一步提高他达拉非的溶出速度和溶出量。本研究表明,SAS-FB法可一步制备他达拉非微丸,在提高难溶性药物溶出度的方面具有应用潜力。

Insoluble drug tadalafil was coated on microcrystalline cellulose(MCC)pellet cores to prepare immediate-release pellets by supercritical anti-solvent fluidization(SAS-FB)coating technology in this paper.The morphology and in vitro dissolution of the pellets were compared with those of tadalafil treated with the supercritical antisolvent(SAS)and the pellets prepared by fluidized bed(FB)coating.The scanning electron micrographs of the pellets prepared by SAS-FB showed that tadalafil was uniformly distributed on the surface of the MCC pellet cores in the form of thin strips,while the pellets produced by FB were coated with bulk crystalline tadalafil.The shape of tadalafil treated with SAS was similar to the bulk drug,clustered in thin strips.Comparing with the other two methods,the pellets prepared by SAS-FB had faster in vitro dissolution rate and higher dissolved percentage.By surface modification of MCC cores with sodium dodecyl sulfate or polyvinylpyrrolidone,the dissolution rate and dissolved percentage of tadalafil pellets prepared by SAS-FB could be further improved.This study showed that the SAS-FB could prepare tadalafil pellets in one step,which had the potential to improve the dissolution of poorly soluble drugs.