Enhanced Apparent Oral Bioavailability of Berberine Through BioSOLVE Technology: Pharmacokinetic Evaluation of Metaberine™.

Abstract

Background Berberine is an isoquinoline alkaloid known for its potential role in supporting metabolic, cardiovascular, and gastrointestinal functions. Its clinical application, however, remains constrained by limited oral absorption, which is influenced by factors such as low solubility, restricted intestinal permeability, metabolism, and transport-mediated efflux. Purpose This study compared the oral pharmacokinetics of Metaberine™, a novel berberine formulation developed with BioSOLVE technology, against conventional berberine in male rats. The objective was to determine whether the formulation enhances peak plasma concentration (C max ) and systemic exposure. Methods Male Sprague-Dawley rats were orally administered the test substance or conventional berberine at a dose of 200 mg/kg body weight. Blood samples were collected at predefined intervals and analyzed for plasma berberine concentrations using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Pharmacokinetic parameters, including area under the plasma concentration-time curve (AUC) from time 0 to 8 h (AUC 0-8 ), 0 to 48 h (AUC 0-48 ), and 0 to infinity (AUC 0-∞ ), peak plasma concentration (C max ), time to reach C max (T max ), apparent terminal half-life (t 1/2 ), and mean residence time (MRT (obs) ) were calculated by non-compartmental analysis. Results There were no treatment-related changes in clinical signs, morbidity, or mortality. The test substance demonstrated higher early systemic exposure and markedly increased peak plasma concentrations compared with conventional berberine. The AUC 0-8 (177.7 ng·h/mL) of test substance was 2.6-fold higher, and C max (139.26 ng/mL) was 11.3-fold higher than those of conventional berberine (68.28 ng·h/mL and 12.32 ng/mL, respectively). Log-transformed analysis showed a significant increase in AUC 0-8 (geometric mean ratio (GMR): 2.07; 90% confidence interval (CI): 1.25-3.41; p < 0.05) and C max (GMR: 6.46; 90% CI: 2.88-14.50; p < 0.05). The AUC 0-48 and AUC 0-∞ were not significantly different between groups. Considering the amount of active berberine, the test substance exhibited 8.6-fold higher AUC 0-8 , 5.5-fold higher AUC 0-48 , and 37.3-fold higher C max per mg/kg active than conventional berberine. The test substance also exhibited a markedly earlier T max (0.5 h vs. 8 h), indicating more rapid systemic appearance of berberine, along with a prolonged apparent terminal half-life (8.63 h vs. 3.64 h). However, T max interpretation is limited by the absence of sampling prior to 0.5 h. Conclusion Overall, Metaberine™ enhanced the apparent oral bioavailability of berberine, primarily through increased early systemic exposure and peak plasma concentration. These findings suggest that the formulation developed using BioSOLVE technology alters the oral pharmacokinetics of berberine under the conditions of this study, supporting further evaluation in additional preclinical and clinical investigations.