Amorphous solid dispersion of berberine with absorption enhancer demonstrates a remarkable hypoglycemic effect via improving its bioavailability.

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 (100mg/kg) improved glucose and lipid metabolism in diabetic rats compared to pure berberine (100mg/kg), berberine tablets (100mg/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.

Zhaojie M ，Ming Z ，Shengnan W ，Xiaojia B ，Hatch GM ，Jingkai G ，Li C ... -  《-》

Preparation, characterization and in vivo studies of amorphous solid dispersion of berberine with hydrogenated phosphatidylcholine.

Berberine, a pure crystalline quaternary ammonium salt with the basic structure of isoquinoline alkaloid, has multiple pharmacological bioactivities. But the poor bioavailability of berberine limited its wide clinical applications. In the present study, we aimed to develop an amorphous solid dispersion of berberine with hydrogenated phosphatidylcholine (HPC) in order to improve its bioavailability. The physical characterization studies such as differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), Fourier transform infrared spectrophotometry (FT-IR) and scanning electron microscopy (SEM) were conducted to characterize the formation of amorphous berberine HPC solid dispersion (BHPC-SD). The everted intestinal sac and single-pass intestinal perfusion study proved that permeability and intestinal absorption of amorphous BHPC-SD was improved compared with that of pure crystalline berberine, and the pharmacokinetic study results demonstrated that the extent of bioavailability was significantly increased as well. However, the dissolution study indicated that the aqueous cumulative dissolution percentages of berberine remained unchanged or even lower by means of preparation into solid dispersion with HPC. Therefore, according to the previous mechanistic studies, the present results supported that it is the enhanced molecularly dissolved concentration (supersaturation) of berberine by transformation from crystalline structure into amorphous solid dispersions that triggers the enhanced permeability, and consequently results in the improved intestinal absorption and bioavailability.

Shi C ，Tong Q ，Fang J ，Wang C ，Wu J ，Wang W ... -  《-》

Solid dispersion of berberine-phospholipid complex/TPGS 1000/SiO₂: preparation, characterization and in vivo studies.

Berberine (Ber), an isoquinoline alkaloid, arouses wide interests in many researchers in recent years because of its numerous new pharmacological actions. However Ber's low oral bioavailability restricts its wide application. In this study, a solid dispersion (BPTS-SD) composed of berberine-phospholipid complex (BPC), D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS 1000) and SiO₂ was prepared by simple solvent evaporation technique. BPC was employed to improve the liposolubility of Ber, and SiO₂ was used to improve the flowability of BPTS-SD, while TPGS 1000 played a dual role: firstly, as a solid dispersion carrier to improve the dissolution rate of BPC and secondly, as a P-glycoprotein (P-gp) inhibitor to enhance the intestinal absorption of Ber. FTIR, DSC and SEM analysis proved the formation of BPC and BPTS-SD. Po/w of BPC successfully increased from 0.25 to 8.75. In vitro dissolution study showed that the cumulative dissolution percentages of BPTS-SDs were nearly 2.67-4.78-folds of BPC. Single-pass intestinal perfusion studies showed that the absorption of Ber in BPC was increased nearly 1.4-2.0-folds compared to that of Ber which was mainly due to the improved liposolubility, and further increased by BPTS-SD around 0.1-1.3-folds compared to that of BPC through the P-gp inhibition of TPGS 1000. Significant improvements in Cmax and AUC₀→t of BPC and BPTS-SD were obtained in pharmacokinetic study (the highest improvement in oral relative bioavailability of BPTS-SD-1 was 322.66% of Ber). All these results indicated that BPTS-SD can be a promising drug delivery system to improve their oral bioavailability for the Ber's analogues. In particular this solid dispersion can be prepared just by a simple method and has a strong feasibility for industrialization.

Zhang Z ，Chen Y ，Deng J ，Jia X ，Zhou J ，Lv H ... -  《-》

Preparation, characterization and in vitro/vivo evaluation of tectorigenin solid dispersion with improved dissolution and bioavailability.

Shuai S ，Yue S ，Huang Q ，Wang W ，Yang J ，Lan K ，Ye L ... -  《-》

In vitro and in vivo studies on a novel solid dispersion of repaglinide using polyvinylpyrrolidone as the carrier.

Yin LF ，Huang SJ ，Zhu CL ，Zhang SH ，Zhang Q ，Chen XJ ，Liu QW ... -  《-》