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

• Published in: Crystal growth & design Vol. 13; no. 7; pp. 3028 - 3035
• Main Authors: Mahé, Nathalie, Nicolaï, Béatrice, Barrio, Maria, Perrin, Marc-Antoine, Do, Bernard, Tamarit, Josep-Lluis, Céolin, René, Rietveld, Ivo B
• Format: Journal Article Publication
• Language: English
• Published: Washington,DC American Chemical Society 03.07.2013
• Subjects: Chemical Sciences; Ciències de la salut; Condensed matter: structure, mechanical and thermal properties; Exact sciences and technology; Farmacologia; Física; Física molecular; Medicina; Pharmaceutical chemistry; Physics; Potassium sulphate; Structure of solids and liquids; crystallography; Structure of specific crystalline solids; Thermal expansion; thermomechanical effects and density; Thermal properties of condensed matter; Thermal properties of crystalline solids; Àrees temàtiques de la UPC; Space groups; Electrostatic interaction; Sulfonates; XRD; Monoclinic lattices; Isomers; Thermal expansion; Unit cell; Quality control; Humidity; Pharmaceutical care; Potassium; Electrostatic force; Crystal structure; thermodynamics; Physical properties
• ISSN: 1528-7483; 1528-7505
• DOI: 10.1021/cg400427v

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.