热熔挤出法制备槲皮素固体分散体

Preparation of Quercetin Solid Dispersion by Hot Melt Extrusion

关键词:  槲皮素  固体分散体  热熔挤出技术  溶出度

Key words:  quercetin  solid dispersion  hot melt extrusion  dissolution

摘要:

目的 采用热熔挤出技术制备难溶性药物槲皮素的固体分散体，提高其溶出速率。方法 以聚丙烯酸树脂(Eudragit EPO)、聚维酮(PVP-K30)、共聚维酮(PVP-VA，Kollidon VA64)为亲水性载体材料，使用双螺杆热熔挤出机制备槲皮素固体分散体，通过体外溶出度测定、差示扫描量热法(DSC)、傅立叶红外光谱(FTIR)和X射线衍射法(XRD)来表征和评价所制备的固体分散体。结果 制备的槲皮素固体分散体，与原料药相比，药物溶出得到显著提高，在人工胃液中3 min时处方槲皮素-EPO(1∶9)的药物溶出度可达到67%，处方槲皮素-木糖醇-PVPK30(1∶3∶6)的药物溶出度可达到65%，而在60 min时原料药溶出度不足10%。XRD图谱显示药物晶体衍射峰消失，DSC图谱显示药物熔点吸热峰消失，提示药物是以无定形态分散在载体材料中。结论 热熔挤出技术可用于制备槲皮素固体分散体，使药物以无定型态高度分散在载体中，溶出度得到显著提高。

Abstract:

OBJECTIVE To improve in vitro dissolution of the poorly water soluble drug quercetin with preparation of its solid dispersion. METHODS Using Eudragit EPO, PVP-K30 or PVP-VA(6∶4) as hydrophilic carrier, the technology of hot melt extrusion (HME) was employed to prepare solid dispersion of quercetin. Fourier transform infrared spectroscopy(FTIR), X-Ray diffraction(XRD) and differential scanning calorimetry(DSC) were employed to characterize the extrusions. RESULTS In vitro dissolution of quercetin from all solid dispersions with EPO or PVPK30 as carrier was significantly improved than that of pure drug. In simulated gastric fluid, the accumulative dissolution of formulation quercetin-EPO (1∶9) reached 67% in 3 min, for formulation of quercetin-xylitol-PVPK30 (1∶3∶6), it reached 65% in 3min, while for pure drug, dissolution was less than 10% in 60min. The results of DSC and XRD showed quercetin was amorphously dispersed in carriers. CONCLUSION Hot melt extrusion can be used to prepare quercetin solid dispersion, from which drug dissolution was significantly improved.