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

TL;DR

This study creates and analyzes new drug combinations of oxicam and metformin to improve solubility, stability, and fluorescence properties for better pharmaceutical performance.

Contribution

A new family of oxicam–metformin salts is developed with enhanced stability and solubility through supramolecular interactions.

Findings

The salts improve metformin stability and protect piroxicam from hydration.

Salt formation increases oxicam solubility while reducing excessive metformin solubility.

Fluorescence behavior is modified due to functional group interactions in the salts.

Abstract

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.

Figures