Multicomponent Oxicam-Metformin Salts: Toward a Strategy for Enhancing Solubility and Stability

Area of Science:

• Materials Science
• Pharmaceutical Chemistry
• Solid-State Chemistry

Background:

• Drug-drug pharmaceutical multicomponent materials (PMMs) are key for modulating drug properties and enabling combination therapy.
• Oxicams (piroxicam, meloxicam, tenoxicam) are nonsteroidal anti-inflammatory drugs with potential for combination therapy.
• Metformin (MTF) is a widely used antidiabetic drug.

Purpose of the Study:

• To prepare and characterize novel oxicam-metformin (MTF) salts.
• To investigate the role of supramolecular synthons in salt formation and structure-property relationships.
• To evaluate the impact of these salts on drug stability, solubility, and fluorescence.

Main Methods:

• Synthesis and full characterization of oxicam-MTF salts.
• X-ray diffraction and computational studies for structural analysis.
• Stability, aqueous solubility, and fluorescence spectroscopy analyses.

Main Results:

• New oxicam-MTF salts were successfully prepared and characterized.
• Supramolecular synthons were identified as crucial for directing salt formation and influencing molecular packing.
• The novel salts enhanced MTF stability and protected piroxicam (PRX) from hydration.
• MTF incorporation increased oxicam solubility, while salt formation moderated MTF's excessive solubility.
• Significant changes in fluorescence behavior were observed due to functional group interactions within the salt frameworks.

Conclusions:

• This study expands the range of known oxicam-MTF salts.
• The findings provide a rational basis for designing solid forms with improved physicochemical properties.
• These PMMs offer a promising strategy for developing enhanced combination therapies.