Preparation and in Vitro-in Vivo Evaluation of Novel Monoammonium Glycyrrhizinate Controlled-porosity Osmotic Pump

Background This study aimed to prepare and evaluate novel monoammonium glycyrrhizinate (MAG) controlled-porosity osmotic pumps with sustained and controlled release properties. Methods Utilizing the impregnation technique, we fabricated the capsule shells and optimized critical factors influencing in vitro release through the Box-Behnken design-response surface methodology. The optimized formulation exhibited a distinct zero-order release pattern for the primary metabolite, glycyrrhetinic acid (GA-30), over 12 hours in vitro. SEM analysis confirmed the successful operation of the Control pore infiltration pump mechanism. Results In vivo, experiments showed that the peak plasma concentrations of GA and glycyrrhizinic acid in rabbits of the prepared capsule were reduced and the mean residence time was prolonged with statistically significant differences compared with the reference formulation, which indicated that the homemade capsule had significantly slow and controlled release characteristics. Molecular docking experiments confirmed the prolongation of the residence time of GA, especially glycyrrhizinic acid, in vivo from the perspective of binding energy. This study also characterized the physical state of MAG and its formulations using differential scanning calorimetry (DSC) and X-ray diffraction (XRD), ensuring the stability of the drug in the formulation. In addition, the in vitro release curve of the controlled-porosity osmotic pump is highly consistent with the expected target curve, verifying the accuracy and reliability of the formulation design. Conclusions This research contributes to the development of an advanced drug delivery system for MAG, enhancing its pharmacological benefits, and offers significant advancements in controlled-release formulations.