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

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.