Amorphous solid dispersion of berberine with absorption enhancer demonstrates a remarkable hypoglycemic effect via improving its bioavailability
Amorphous solid dispersion of berberine with absorption enhancer demonstrates a remarkable hypoglycemic effect via improving its bioavailability
复制标题
含吸收促进剂的小檗碱无定形固体分散体通过提高其生物利用度显示出显着的降血糖作用
DOI：
10.1016/j.ijpharm.2014.03.017
复制
发表时间：
2014-06-05
影响因子：
5.8
通讯作者：
Chen Li
中科院分区：
文献类型：
--
作者：
Meng Zhaojie;Zhang Ming;Chen Li
由于溶解度和膜渗透性差，小檗碱的口服生物利用度低，限制了其在糖尿病治疗中的临床应用。研究了黄桂固体分散体（HGSD）制剂对黄连素溶出度和口服生物利用度的改善作用。采用溶剂蒸发法制备了HGSDs，并用x射线衍射、差示扫描量热法和扫描电镜对其进行了表征。根据体外溶解度和溶出度的研究，通过正交试验筛选出第9个HGSDs产品P9。通过体外膜透性、原位肠灌注和体内生物利用度评价P9在大鼠体内的药动学行为。并在2型糖尿病大鼠模型中检测P9的抗糖尿病作用。发现P9中大部分小檗碱以无定形存在，其溶解度和溶出率显著提高。药代动力学研究表明，与小檗碱或小檗碱片相比，P9的体外膜透性增加了3倍，原位肠灌注增加了4倍，体内生物利用度增加了5倍。此外，与纯小檗碱（100 mg/kg）、小檗碱片（100 mg/kg）或二甲双胍（300 mg/kg）治疗相比，口服P9 （100 mg/kg）改善了糖尿病大鼠的葡萄糖和脂质代谢。这些发现表明P9提高了小檗碱的口服生物利用度，可能是治疗糖尿病的潜在候选药物。(C) 2014, Elsevier b.v.出版。
Low oral bioavailability of berberine due to poor solubility and membrane permeability limits its clinical use for treatment of diabetes. We developed an amorphous solid dispersion of berberine with absorption enhancer sodium caprate, referred to as Huang-Gui Solid Dispersion (HGSD) preparations, and examined them for improvement of dissolution and oral bioavailability. HGSDs were prepared by solvent evaporation, and the formulations of amorphous solid dispersions were characterized by X-ray diffraction, differential scanning calorimetry and scanning electron microscopy. According to in vitro solubility and dissolution studies, P9, the 9th production of HGSDs based on orthogonal test, was sorted out. Then pharmacokinetic behavior of P9 was evaluated by in vitro membrane permeation, in situ intestinal perfusion, and in vivo bioavailability in rats. Furthermore, the anti-diabetic effect of P9 was examined in a type 2 diabetic rat model. It was found that majority of berberine in P9 existed in an amorphous form, and its solubility and dissolution rate were significantly increased. Pharmacokinetic studies demonstrated a 3-fold increase in in vitro membrane permeation, a 4-fold increase in in situ intestinal perfusion and a 5-fold increase in vivo bioavailability of P9 compared to berberine or berberine tablets. In addition, oral administration of P9 (100 mg/kg) improved glucose and lipid metabolism in diabetic rats compared to pure berberine (100 mg/kg), berberine tablets (100 mg/kg) or metformin (300 mg/kg) treatment. These findings indicate that P9 enhances oral bioavailability of berberine and may be a potential candidate drug for treatment of diabetes. (C) 2014 Published by Elsevier B. V.