Design of Potential Pharmaceutical-Based Metal Complexes Derived from Cromolyn a Mast Cell Stabilizer.

Abstract

A series of pharmaceutical metal complexes (pMCs) were produced and characterized using the mast cell stabilizer, cromolyn, and bioactive metal ions (Zn+2, Mg+2, and Ca+2). Three novel pMCs, Cromolyn-Zn, Cromolyn-Mg, and Cromolyn-Ca, were formed through reactions under controlled temperature and pH conditions. Additional characterization for these materials was performed employing a number of solid-state characterization techniques, such as thermogravimetric analysis (TGA), powder and single-crystal X-ray diffraction (PXRD and SCXRD), and scanning electron microscopy coupled with energy-dispersive spectroscopy (SEM-EDS). TGA demonstrated that these metal complexes showed an enhanced thermal stability due to the strong coordination with the ligand, cromolyn. PXRD data indicates a high degree of crystallinity as well as a unique packing arrangement for each pMCs. SEM analysis showed materials with well-defined morphologies, while EDS presented elemental evidence for the unique composition of each pMCs. The crystal structure for these materials was elucidated through SCXRD, and a variety of binding modes and packing motifs were found within each respective metal complex. Only two-dimensional (2D) structures were achieved under the conditions studied. These binding modalities might affect the activity and delivery of cromolyn sodium (CS). The stability of the metal complexes was assessed in phosphate-buffered saline (PBS, pH = 7.40) and fasted-state simulated gastric fluids (FaSSGF, pH = 1.60). Dissolution studies show high stability and slow degradation for the metal complexes, while a higher dissolution was observed for the drug compound in PBS. Neither CS nor the pMCs dissolved significantly in FaSSGF at 37 °C.