Tranilast-matrine co-amorphous system: Strong intermolecular interactions, improved solubility, and physiochemical...

Area of Science:

• Pharmaceutical Science
• Drug Delivery Systems
• Materials Science

Background:

• Biopharmaceutics Classification System (BCS) class II and IV drugs exhibit poor aqueous solubility, limiting their therapeutic efficacy.
• Tranilast (TRA), an anti-allergic medication, is a BCS class II drug with low solubility, impacting its in vivo absorption.
• Existing co-amorphous systems often provide only limited solubility enhancements.

Purpose of the Study:

• To develop a novel co-amorphous system of tranilast (TRA) and matrine (MAR) to significantly improve the solubility and dissolution of TRA.
• To investigate the intermolecular interactions and physical stability of the TRA-MAR co-amorphous system.
• To evaluate the potential of co-amorphization for enhancing the delivery of poorly soluble drugs.

Main Methods:

• Solubility parameter and phase solubility experiments guided the selection of matrine (MAR) for co-amorphization with TRA.
• Co-amorphous TRA-MAR system prepared using the solvent evaporation method.
• Characterization involved powder X-ray diffraction, modulated temperature differential scanning calorimetry, Fourier transform infrared spectroscopy, FT-Raman, X-ray photoelectron spectroscopy, and molecular dynamics simulations.
• In vitro release experiments and NMR spectroscopy were used to assess solubility, dissolution, and intermolecular interactions.

Main Results:

• The TRA-MAR co-amorphous system demonstrated strong intermolecular interactions, including salt formation and hydrogen bonding, confirmed by spectroscopic and simulation studies.
• The co-amorphous system exhibited excellent physical stability under tested conditions.
• Co-amorphous TRA-MAR achieved a significant solubility enhancement (greater than 100-fold) and rapid in vitro release.
• NMR spectroscopy confirmed strong intermolecular interactions between TRA and MAR in various solvents.

Conclusions:

• The developed TRA-MAR co-amorphous system effectively overcomes the poor solubility of tranilast.
• Co-amorphization with matrine presents a promising strategy for significantly improving the solubility and dissolution of BCS class II and IV drugs.
• This approach holds great potential for advancing drug delivery systems for poorly soluble pharmaceuticals.