To improve the aqueous solubility and the oral bioavailability of a poorly water-soluble biologically active pentacyclic triterpenoid, ursolic acid (UA), ursolic acid-phospholipid complex (UA-PC) was prepared using solvent-assisted grinding method which is green and simple. The phospholipid complex was characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), scanning electron microscope (SEM), and transmission electron microscope (TEM), which confirmed the formation of the phospholipid complex. Specifically, compared with free UA, the formulation demonstrated over 276-fold higher aqueous solubility of UA and exhibited faster dissolution rate and higher cumulative dissolution percentages. Finally, the oral bioavailability of the prepared UA-PC was evaluated using Sprague-Dawley (SD) rats. Compared with free UA, the UA-PC exhibited considerable enhancement in the bioavailability with an increase in Cmax (183.80 vs 68.26 μg/l) and AUC 0-24 h (878.0 vs 212.1 μg·h/l), which was consistent with the in vitro results. This enhancement was attributed to the improvement of solubility and dissolution in vitro. Therefore, the method of solvent-assisted grinding appears to be an efficient approach for the preparation of UA-PC, and the prepared UA-PC showed a promising potential to overcome the limitation of poor oral bioavailability associated with low water solubility.

中文翻译：

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采用溶剂辅助研磨法制备熊果酸-磷脂复合物以提高溶出度和口服生物利用度。


为了提高难溶于水的生物活性五环三萜类化合物的水溶性和口服生物利用度，采用绿色、简单的溶剂辅助研磨法制备了熊果酸（UA）、熊果酸磷脂复合物（UA-PC）。通过差示扫描量热法（DSC）、粉末X射线衍射（PXRD）、扫描电子显微镜（SEM）和透射电子显微镜（TEM）对磷脂复合物进行表征，证实了磷脂复合物的形成。具体而言，与游离 UA 相比，该制剂的 UA 水溶性高出 276 倍以上，并表现出更快的溶出速率和更高的累积溶出百分比。最后，使用 Sprague-Dawley (SD) 大鼠评估制备的 UA-PC 的口服生物利用度。与游离UA相比，UA-PC的生物利用度显着提高，Cmax（183.80 vs 68.26 μg/l）和AUC 0-24 h（878.0 vs 212.1 μg·h/l）有所增加，这与游离UA一致。体外结果。这种增强归因于体外溶解度和溶出度的改善。因此，溶剂辅助研磨方法似乎是制备 UA-PC 的有效方法，并且所制备的 UA-PC 在克服与低水溶性相关的口服生物利用度差的限制方面表现出良好的潜力。