Solid-State Properties and Dehydration Behavior of the Active Pharmaceutical Ingredient Potassium Guaiacol-4-sulfonate

Potassium guaiacolsulfonate is an
active pharmaceutical ingredient
that has been in use for more than a century, and it is still widely
used in cough syrups. Nonetheless, no crystal structure has ever been
determined to facilitate quality control. This is all the more surprising
because two isomers are known to exist. A commercial sample has been
studied by X-ray diffraction and thermogravimetric methods. It consists
of potassium guaiacol-4-sulfonate, and it crystallizes in the monoclinic
space group C2/c as a hemihydrate.
The crystals exhibit uniaxial negative thermal expansion, and the
electrostatic forces between the ions appear to be the major driving
force of the observed displacements. Dehydration of the hemihydrate
was observed above 380 K. The anhydrate has a structure similar to
the hemihydrate with almost the same unit cell parameters. The dehydration
kinetics points to a displacive mechanism; water molecules are located
in channels, through which they leave the crystal. The structural
readjustments that occur to accommodate the loss of water are driven
by electrostatic interactions between the ions similar to the displacements
observed for thermal expansion. Under ambient conditions (and humidity),
the anhydrate is not stable and transforms into the hemihydrate.