Dry state microcrystals stabilized by an HPMC film to improve the bioavailability of andrographolide.
Dry state microcrystals stabilized by an HPMC film to improve the bioavailability of andrographolide.
复制标题
DOI：
10.1016/j.ijpharm.2015.07.057
复制
发表时间：
2015-09
影响因子：
5.8
通讯作者：
Yu Zhang;Xi Hu;Xiaolin Liu;Yun Dandan;Donghua Di;Tian Yin;Shu Zhang;Xing Tang
中科院分区：
文献类型：
--
作者：
Yu Zhang;Xi Hu;Xiaolin Liu;Yun Dandan;Donghua Di;Tian Yin;Shu Zhang;Xing Tang
目的：研究穿心莲内酯（ADG）的体外溶出度和体内生物利用度。方法：采用实验室篮式粉碎机制备穿心莲内酯混悬液，然后用流化床包衣机将其铺在微晶纤维素（MCC）微丸上，制成固体微丸。采用光学显微镜、粒度分布研究、差示扫描量热法（DSC）和粉末X射线衍射（PXRD）对湿磨悬浮液进行表征。此外，ADG颗粒进行了调查，涉及扫描电子显微镜（SEM），以及溶解，加速稳定性和生物利用度measurements.ResultsThe粒径显着降低（从31.6 μm至2.17 μm），然而，ADG悬浮液中保留其结晶度所示的DSC和PXRD的调查结果。新微丸和市售滴丸在纯水中60 min的溶出度分别为95.6%和48%。在6个月的加速试验（40 °C和RH 75%）后，尽管初始溶出速率略有下降，但在60分钟内新颗粒的总体溶出几乎与新鲜制备的颗粒一样高。在体内评价中，Cmax（87.54 ± 54.82 μg/L）和AUC（0−t）（495.86 ± 281.05 μg/L·h）明显高于滴丸（30.88 ± 12.02 μg/L，301.07 ± 133.85 μg/L h），而供试品的Tmax短于参比品结论以羟丙甲纤维素（HPMC）为稳定剂的ADG微晶微丸，可显著提高穿心莲内酯的溶出度和生物利用度。
ObjectiveThe main purpose of this study was to improve thein-vitrodissolution and thein-vivobioavailability of a poorly water-soluble drug, andrographolide (ADG).MethodsA wet-milled suspension was prepared using a Lab basket mill in the presence of a hydrophilic carrier solution and then it was layered on to MCC beads with a fluidized bed coater to obtain solidified pellets. Optical microscopy, particle size distribution investigation, differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) were used to characterize the wet-milled suspension. In addition, the ADG pellets were subjected to investigations involving scanning electron microscopy (SEM), as well as dissolution, accelerated stability and bioavailability measurements.ResultsThe particle size was significantly reduced (from 31.6 μm to 2.17 μm), however, the ADG in suspension retained its crystallinity as shown by the results of the DSC and PXRD investigations. The dissolution of the new pellets and commercial dripping pills was 95.6% and 48%, respectively, in pure water over 60 min. After a 6 month accelerated test (40 °C and RH 75%), although the initial dissolution rate declined slightly, the overall dissolution of the new pellets within 60 min was almost as high as the freshly prepared pellets. In thein-vivoevaluation, theCmax(87.54 ± 54.82 μg/L) and AUC(0−t)of the new pellets (495.86 ± 281.05 μg/L h) were clearly higher than those of the dripping pills (30.88 ± 12.02 μg/L, 301.07 ± 133.85 μg/L h), while theTmaxof the test preparation was shorter than that of the reference (1.38 hvs3.29 h).ConclusionThese results showed that the new core–shell structured pellets consisting of ADG microcrystalline particles and stabilized by HPMC alone, markedly improved the dissolution and bioavailability of andrographolide.