Self-Microemulsifying Drug Delivery System to Enhance Oral Bioavailability of Berberine Hydrochloride in Rats

Abstract

Berberine hydrochloride (BH) is a versatile bioactive compound derived from the plants of the Berberis genus, known for its various pharmacological effects. However, its oral bioavailability is low due to its high hydrophilicity and limited permeability. To enhance its clinical efficacy and oral bioavailability, this study designed and prepared a BH-loaded self-microemulsifying drug delivery system (BH-SMEDDS), and characterized its in vitro and in vivo properties. Firstly, the optimal formulation of BH-SMEDDS was selected using solubility evaluations, pseudo-ternary phase diagrams, and particle size analysis. The formulation containing 55% Capmul MCM, 22.5% Kolliphor RH 40, and 22.5% 1,2-propanediol was developed. BH-SMEDDS exhibited stable physicochemical properties, with an average particle size of 47.2 ± 0.10 nm and a self-emulsification time of 26.02 ± 0.24 s. Moreover, in vitro dissolution studies showed significant improvements in BH release in simulated intestinal fluid, achieving 93.1 ± 2.3% release within 300 min. Meanwhile, BH-SMEDDS did not exhibit cytotoxic effects on the Caco-2 cells. Additionally, BH-SMEDDS achieved a 1.63-fold increase in oral bioavailability compared to commercial BH tablets. Therefore, SMEDDS presents a promising strategy for delivering BH with enhanced oral bioavailability, demonstrating significant potential for clinical application.