Pakistan Journal of Pharmaceutical Sciences

Abstract: Background: Piroxicam, a widely used NSAID, suffers from poor aqueous solubility, limited bioavailability and adverse gastrointestinal effects. Hybrid drug delivery systems combining organic carriers, metal complexes and supramolecular assemblies offer a promising strategy to overcome these limitations. Objectives: To design and characterize a multifunctional hybrid drug delivery system integrating cobalt-substituted meso-tetra (4-carboxyphenyl) porphyrin (TCPP-Co), ?-cyclodextrin and piroxicam, with the goal of enhancing solubility, structural reorganization and controlled release. Methods: The hybrid system was synthesized in ethanol and characterized using UV-Vis, FTIR, ¹H NMR, XRD and SEM. In-vitro release studies were performed in simulated gastric fluid and phosphate buffer, with kinetic modeling applied using Korsmeyer–Peppas, Higuchi and zero-order, first-order and Hixson–Crowell equations. Results: Spectroscopic analyses confirmed supramolecular interactions through bathochromic shifts, broadened O–H and C=O vibrations and altered proton environments. XRD revealed amorphization, while SEM showed porous, fused morphologies. Drug release kinetics yielded a release exponent n?0.66, indicating anomalous transport governed by both diffusion and matrix relaxation. The Hixson–Crowell model (R² = 0.993) supported surface erosion, while other models confirmed hybrid release behavior. Conclusion: The TCPP-Co/?-cyclodextrin/piroxicam hybrid system demonstrates enhanced solubility, disrupted crystallinity and controlled release dynamics. This supramolecular assembly validates the potential of metalloporphyrin–cyclodextrin hybrids as advanced NSAID delivery platforms with improved therapeutic performance.