Department of Pharmaceutics, National Institute of Pharmaceutical Education & Research (NIPER)-Guwahati, Changsari, Assam, India.
National Centre for Pharmacoengineering, NIPER-Guwahati, Changsari, Assam, India.
AAPS PharmSciTech. 2022 Mar 16;23(4):89. doi: 10.1208/s12249-022-02241-9.
The low oral bioavailability, short biological half-life, high dose, and frequent dosing of berberine (BBR) contribute to its restricted clinical use despite its extensive pharmacological activity. Thus, the objective of this study was to formulate sustained-release microparticles (MPs) using a pH-independent release polymer and to evaluate their potential to improve the oral bioavailability of BBR. BBR loaded MPs were prepared using the emulsion crosslinking method and evaluated for particle size, circularity, morphology, entrapment efficiency, solid-state analysis, swelling index, and in vitro BBR release study fitted with different models of release kinetics. The MPs exhibited desired particle sizes ranges between 11.09-11.62 μm and were almost spherical in shape, as confirmed by the circularity value and micrographic images. A loss of BBR crystallinity was observed after encapsulation in MPs, as evident from various solid-state analyses. The final optimized batch (F3) showed highest % BBR entrapment efficiency value of 81.63% ± 4.9. The in vitro BBR release performance in both acidic and alkaline media showed the desired sustained release behavior from the crosslinked MPs, where the maximum BBR release was observed at alkaline pH, which is in accordance with the swelling study data. In the in vivo study, the oral absorption profiles of BBR from both pristine and MPs formats were investigated using in-house prototyped 3D printed hollow capsules as a unit dose carrier. In vivo data showed sustained and prolonged absorption behavior of BBR from MPs compared to their pristine counterparts, which resulted in a cumulative increment of relative oral bioavailability to mitigate the aforementioned issues related to BBR. Graphical Abstract.
尽管小檗碱（BBR）具有广泛的药理活性，但由于其口服生物利用度低、生物半衰期短、剂量高、用药频率高，限制了其临床应用。因此，本研究的目的是使用一种 pH 独立释放的聚合物来制备缓释微球（MPs），并评估其提高 BBR 口服生物利用度的潜力。采用乳化交联法制备 BBR 载药 MPs，并对其粒径、圆度、形态、包封效率、固态分析、溶胀指数和体外 BBR 释放进行评价，拟合不同的释放动力学模型。 MPs 的粒径在 11.09-11.62 μm 之间，形状几乎为球形，这一点可以通过圆度值和显微图像得到证实。包封在 MPs 中后，BBR 的结晶度丧失，这从各种固态分析中可以明显看出。最终优化批次（F3）的 BBR 包封效率最高，为 81.63%±4.9。在酸性和碱性介质中的体外 BBR 释放性能表明，交联 MPs 具有理想的持续释放行为，在碱性 pH 下观察到最大的 BBR 释放，这与溶胀研究数据一致。在体内研究中，使用内部原型 3D 打印空心胶囊作为单位剂量载体，研究了 BBR 从原药和 MPs 两种剂型的口服吸收情况。体内数据显示，与原药相比，BBR 从 MPs 中呈现出持续和延长的吸收行为，从而使相对口服生物利用度得到累积增加，以缓解与 BBR 相关的上述问题。
