Solid-State Chemistry of Cromolyn Sodium (Disodium Cromoglycate)

A detailed crystallographic study was made to provide a better understanding and control of processing steps, purity control, and dosage formulations of cromolyn sodium. The compound, an odorless, white, hydrated crystalline powder, is the disodium salt of the dibasic acid: 1,3-bis(2-carboxychromon-5-yloxy)-2-hydroxypropane. No crystalline polymorphs were observed, but the crystals can quickly absorb (or lose) water as a continuous series of interstitial solid solutions. The amount of water absorbed or lost is proportional to the relative humidity of the environment of the crystals. At 90% R.H., the interstitial water approaches 24 wt. %, or nine molecules per molecule of cromolyn sodium. The absorbed water causes the lattice to expand reversibly, especially in the b crystallographic direction, and this results in remarkable changes in the X-ray diffraction pattern, density, and other physical properties. Above about 93% R.H., the compound absorbs more water than the crystals can hold. They then collapse to form one of two lyotropic mesophases, containing up to about 260 molecules of water per molecule of cromolyn sodium at 20° or about 10 wt. % cromolyn sodium.