热熔挤出技术制备小檗红碱固体分散体及其体外评价

Preparation and in vitro evaluation of berberrubine solid dispersion

关键词:  热熔挤出技术  小檗红碱  固体分散体  体外释放

Key words:  hot-melt extrusion  berberrubine  solid dispersion  in vitro release behavior

摘要:

[目的]采用热熔挤出技术制备微溶性药物小檗红碱的固体分散体，以提高其溶解度，延缓其体外释放行为。[方法]以Soluplus^® 为载体，采用同螺杆热熔挤出机制备小檗红碱固体分散体，通过差示扫描量热（DSC）分析、粉末X射线衍射（XRD）分析、扫描电子显微镜（SEM）观察和傅里叶变换红外光谱（FT-IR）分析对制备的固体分散体进行表征，并考察挤出物在不同介质中的溶解度和体外溶出度。[结果]DSC和XRD分析结果显示，固体分散体中小檗红碱的主要特征峰减弱甚至部分消失，SEM结果表明固体分散体为无规则形态。FT-IR结果表明小檗红碱与Soluplus^®之间可能存在氢键作用。所制备的小檗红碱固体分散体在pH 6.8的磷酸盐缓冲液中溶解度为原料药的2.59倍。体外溶出度结果显示，小檗红碱固体分散体具有明显缓释作用。[结论]成功制备了小檗红碱固体分散体，且能显著提高其溶解度，并延缓其体外释放行为。

Abstract:

[Objective] To prepare a solid dispersion of the sparingly soluble drug berberrubine by hot melt extrusion to increase its solubility and delay its in vitro release behavior.[Methods] A solid dispersion of berberrubine was prepared by homo twin-screw extrusion using Soluplus^® as the carrier. The prepared solid dispersion was characterized by differential scanning calorimetry (DSC) analysis,powder X-ray diffraction (XRD) analysis, scanning electron microscopy (SEM) observation and Fourier transform infrared spectroscopy (FT-IR) analysis. The solubility and in vitro dissolution of the solid dispersion were investigated in different media.[Results] The results of DSC and XRD analysis showed that the main characteristic peaks of berberrubine in the solid dispersion weakened or even partially disappeared,and the SEM results showed that the solid dispersion was irregular. The FT-IR results indicate that there is hydrogen bonding between the berberrubine and Soluplus^®. The prepared solid dispersion of berberrubine had a solubility of 2.59 times that of the drug substance in a phosphate buffer of pH 6.8. The results of dissolution in vitro showed that berberrubine solid dispersion had an obvious sustained release effect.[Conclusion] The solid dispersion of berberrubine was successfully prepared,and its solubility was significantly improved,and its release behavior in vitro was delayed.