利伐沙班固体分散体的制备及体外溶出

Preparation and in vitro Dissolution of Rivaroxaban Solid Dispersions

分别以亲水性高分子材料聚乙二醇6000(PEG 6000)、聚乙烯吡咯烷酮(PVP K30)、共聚维酮(coPVP)作载体,以溶剂法制备利伐沙班固体分散体,并进行体外溶出研究。采用差示扫描量热法(DSC)、X-射线衍射法(XRD)及扫描电镜法(SEM)对制备的固体分散体进行物相鉴别。结果表明,当利伐沙班与coPVP质量比为1∶10、反应时间为45 min、反应温度为65℃时,制得的固体分散体体外溶出效果最好,5 min时固体分散体的溶出度为利伐沙班原料药的5.2倍,20 min内溶出率达到96.8%。物相鉴别表明利伐沙班以无定形高度分散于高分子载体coPVP中,证明了固体分散体的形成。

Polyethylene glycol 6000（PEG 6000）, polyvinylpyrrolidone（PVP） K30 and copolyvinylpyrrolidone（coPVP） were respectively used as carriers to prepare solid dispersions（SDs） of rivaroxaban by solvent method, and the dissolution characteristics in vitro were studied. According to the results of single factor test, the optimal preparation of rivaroxaban SDs was as follows： the SDs with coPVP as carriers and drug/carrier ratio of 1∶10 were prepared at 65 ℃and rotating time of 45 min. Physicochemical properties of the obtained SDs were investigated by differential scanning calorimetry（DSC）, X-ray diffraction（XRD） and scanning electron microscopy（SEM）. The dissolution of rivaroxabancoPVP SDs at 5 min was 5.2 times as much as the bulk drug and reached 96.8% at 20 min. The results of DSC, XRD and SEM analyses showed that rivaroxaban was highly dispersed in polymer carrier coPVP with amorphous form, which proved the formation of solid dispersion.