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.