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

Drug-drug pharmaceutical multicomponent materials (PMMs) offer a promising strategy to modulate the physicochemical properties of active pharmaceutical ingredients, while enabling synergistic effects and combination therapy. Here, we report the preparation and full characterization of a new family of oxicam-metformin (MTF) salts, involving the nonsteroidal anti-inflammatory drugs piroxicam (PRX), meloxicam (MLX), and tenoxicam (TNX). Structural and computational studies revealed the role of supramolecular synthons in directing the salt formation and highlighted the relationship between molecular packing and physicochemical properties. Stability analyses showed that these materials enhance MTF stability, while particularly protecting PRX from hydration. Importantly, incorporation of MTF increased the aqueous solubility of the oxicams, while salt formation moderated the excessive solubility of free MTF. Significant modifications in fluorescence behavior were also observed, arising from interactions between functional groups involved in the fluorescence procedure within the frameworks. Overall, this study broadens the structural and functional landscape of oxicam-MTF salts and provides a rational framework for designing solid forms with improved stability and solubility.