Formulation and in vitro-in vivo assessment of a novel monoammonium glycyrrhizinate controlled-porosity osmotic pump.

Abstract

This study aimed to prepare and evaluate a novel monoammonium glycyrrhizinate (MAG) controlled-porosity osmotic pump (CPOP) with controlled-release properties. Capsule shells were prepared by the dip-coating method method, and the key variables affecting in vitro release were optimized using a Box-Behnken design-response surface methodology. In vitro release behavior was evaluated, and scanning electron microscopy (SEM) was used to examine shell morphology before and after dissolution. Pharmacokinetic behavior in rabbits, molecular docking, and solid-state characterization by differential scanning calorimetry (DSC) and X-ray diffraction (XRD) were also performed. The optimized formulation exhibited a near zero-order release profile of MAG over 12 h in vitro, and the release curve closely matched the target profile. In rabbits, the self-prepared capsules reduced the peak plasma concentrations of MAG and its active metabolite glycyrrhetinic acid (GA) and significantly prolonged mean residence time compared with the reference formulation, indicating marked controlled-release behavior in vivo. Molecular docking confirmed stable binding of GA to nuclear factor erythroid 2-related factor 2 (Nrf2) and peroxisome proliferator-activated receptor gamma (PPARγ), providing a mechanistic basis for the pharmacological benefits associated with prolonged in vivo exposure. DSC and XRD further showed that MAG remained in a stable crystalline state, with no crystal-form transition or incompatibility with the excipients during preparation. This study provides a promising advanced drug-delivery system for MAG, enhances understanding of its pharmacological advantages, and offers useful guidance for the development of controlled-release formulations.

Key Findings

• A novel monoammonium glycyrrhizinate (MAG) controlled-porosity osmotic pump (CPOP) was successfully formulated with near zero-order release over 12 hours in vitro.
• In vivo pharmacokinetic studies in rabbits showed reduced peak plasma concentrations and prolonged mean residence time of MAG and its active metabolite glycyrrhetinic acid (GA), demonstrating effective controlled-release behavior.
• Molecular docking revealed stable binding of GA to Nrf2 and PPARγ, suggesting a mechanistic basis for the pharmacological benefits of prolonged exposure.
• Solid-state characterization confirmed MAG remained stable and compatible with excipients during formulation.

Clinical Significance

Citation

Lu Xuan, Yang Hongfei, Chen Jian-Liet al.. Formulation and in vitro-in vivo assessment of a novel monoammonium glycyrrhizinate controlled-porosity osmotic pump. Scientific reports. 2026-May-02.