Solid-State Synthesis Based on Natural Leucomisine

Area of Science:

• Pharmacology and Phytochemistry
• Materials Science
• Drug Delivery Systems

Background:

• Leucomisine, a sesquiterpene γ-lactone from Artemisia leucodes, possesses valuable therapeutic properties.
• Its pharmaceutical application is hindered by poor aqueous solubility and low bioavailability.
• Developing strategies to improve leucomisine's solubility is crucial for its medicinal use.

Purpose of the Study:

• To investigate the solid-state synthesis of leucomisine using disodium glycyrrhizinate as a carrier.
• To evaluate the impact of different synthesis methods on leucomisine's aqueous solubility and dissolution rate.
• To elucidate the mechanisms behind solubility enhancement.

Main Methods:

• Solid-state synthesis of leucomisine-disodium glycyrrhizinate complexes via solvent removal, simple mixing, and mixture heating.
• Physicochemical characterization using visible-range spectrophotometry, microcrystalloscopy, optical property analysis, and X-ray phase analysis.
• Quantification of solubility and dissolution rate improvements.

Main Results:

• Synthesized solid dispersions demonstrated a 7-19-fold increase in leucomisine solubility.
• Dissolution rates were significantly enhanced, showing a 36-100-fold increase.
• The "simple mixing" method yielded the most substantial improvements in dissolution.

Conclusions:

• Solid-state synthesis effectively enhances leucomisine's aqueous solubility and dissolution rate.
• Mechanisms include loss of crystallinity, micronization, carrier-mediated solubilization, and colloidal solution formation.
• Disodium glycyrrhizinate is a promising carrier for improving leucomisine's bioavailability.