Improving pharmacokinetics and pharmacodynamics of berberine hydrochloride using solid dispersion: A therapeutic approach to hyperlipidemia

Abstract

Berberine is an isoquinoline alkaloid that acts as a natural PCSK9 inhibitor. By inhibiting PCSK9, it upregulates Low-Density Lipoprotein (LDL) receptors and helps maintain lipid metabolism. Although it is a promising hypolipidemic agent, its clinical application is limited by poor solubility, low permeability, and extensive first-pass metabolism. To overcome these limitations, this study aimed to design, formulate, and evaluate an optimized ternary solid dispersion of berberine. A full factorial design was employed for the formulation process. The resulting ternary solid dispersion was characterized by its solubility, permeability, % drug release, and was further analyzed using Differential Scanning Calorimetry (DSC), Fourier-Transform Infrared Spectroscopy (FTIR), Powder X-Ray Diffraction (P-XRD), and Scanning Electron Microscopy (SEM). The results from these analyses confirmed the successful formation of the ternary solid dispersion. The pharmacokinetic performance was quantified using a validated HPLC method, while the pharmacodynamic efficacy was assessed by measuring biochemical parameters in a high-fat diet animal model. The formulation demonstrated a 22-fold increase in solubility, a 4.17-fold higher maximum concentration (Cmax), and a 6.93-fold greater area under the curve (AUC), indicating faster absorption compared to the API. A significant reduction in lipid parameters including LDL cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG) was also observed. In conclusion, the findings indicate that the ternary solid dispersion formulation significantly enhances the bioavailability of berberine and represents a potential candidate for treating hyperlipidemia.