不同载药量姜黄素自纳米乳体外分散后相行为与稳定性的相关性考察

Investigation on Correlation of Phase Behavior and Stability of Curcumin Self-nanoemulsion with Different Drug Loading After in Vitro Dispersion

目的:研究不同载药量姜黄素自纳米乳(CUR-SNEDDS)在人工胃肠液中分散相行为与纳米乳稳定性的关系。方法:以CUR过饱和度-时间曲线的变化趋势表示CUR-SNEDDS分散后沉淀生长速度,分别采用紫外-可见光谱法和偏振光显微镜考察载药量对晶体成核与生长的影响,利用X射线粉末衍射(XRD)和差示扫描量热法(DSC)分析不同载药量CURSNEDDS在人工胃肠液中沉淀存在形式,同时考察载药量对CUR-SNEDDS在人工胃肠液中形成的纳米乳稳定性的影响。结果:在人工胃肠液中,随着载药量的提高,CUR过饱和度-时间曲线下面积越大(100%载药量≈90%载药量>75%载药量),结晶成核与生长速度加快(100%载药量>90%载药量>75%载药量),沉淀组成中无定型比例减小,分散后形成的纳米乳滴黏连且分布不均匀、粒径与分散性增大。结论:高载药量促进了晶体成核与生长,增大了沉淀组成中晶型比例,从而导致形成的纳米乳稳定性下降,建议CUR-SNEDDS载药量控制在90%以下。

Objective: To investigate the relationship between phase behavior of curcumin(CUR from self-nanoemulsion drug delivery system(SNEDDS)and stability of the formed nanoemulsion in artificial gastrointestinal fluid. Method: The growth rate of precipitation after dispersion of CUR-SNEDDS was expressed by the change tendency of CUR supersaturation-time curve. The effect of drug loading on crystal nucleation and growth was investigated by ultraviolet-visible spectrometry and polarized light microscope,respectively. X-ray powder diffraction(XRD)and differential scanning calorimetry(DSC)were used to analyze the precipitation forms of CUR-SNEDDS with different drug loading in artificial gastrointestinal fluid. At the same time,the effect of drug loading on the quality stability of nanoemulsion formed by CUR-SNEDDS in artificial gastrointestinal fluid was investigated. Result: In the artificial gastrointestinal fluid,with the increase of drug loading,the area under the supersaturation-time curve of CUR was increased(100% drug loading≈90%drug loading>75% drug loading),the crystallization nucleation and growth rate were accelerated(100% drug loading>90% drug loading>75% drug loading),the amorphous proportion in the precipitation composition decreased,the nanoemulsion droplets adhered and distributed unevenly,the particle size and dispersivity were increased. Conclusion: High drug loading promotes the nucleation and growth of crystals,and increases the proportion of crystal forms in the precipitation composition,which leads to the decrease in the stability of the formed nanoemulsion. Therefore,it is suggested that the drug loading of CUR-SNEDDS needs to be controlled below 90%.