Physicochemical Properties and Method for Determination of Potassium Guaiacolsulfonate

Abstract

The physicochemical properties of potassium guaiacol-4-sulfonate (I) and -S-suIfonate (II) have been investigated. Analyses of the X-ray diffraction patterns, infrared spectra, and thermogravimetric and differential scanning calorimetric curves showed that I occurs as crystals that are anhydrous or hydrated up to ⅔ mole (4.8%) and that II occurs as crystals that are anhydrous or dihydrated (13.5%). Solutions of I and II at various pH values showed almost the same UV spectra at <pH 6.0 but very different UV spectra >pH 7.0. Most commercially available potassium guaiacolsulfonate consists predominantly of potassium guaiacol-4-sulfonate (as determined by UVabsorption measurements and liquid chromatography).

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

“…Kawamura et al found that the powder diffraction pattern of PGS hemihydrate changed considerably after 2 h at 443 K under vacuum. 2 This was interpreted as formation of an anhydrate form; however, they did not quantify how much of the sample had converted. 2 In the present study, the formation of a structure different from the hemihydrate can be observed in Figure 9; additional Bragg peaks can be observed in the X-ray diffraction patterns from 430 K on indicating that the initial crystalline phase is changing.…”

“…2 This was interpreted as formation of an anhydrate form; however, they did not quantify how much of the sample had converted. 2 In the present study, the formation of a structure different from the hemihydrate can be observed in Figure 9; additional Bragg peaks can be observed in the X-ray diffraction patterns from 430 K on indicating that the initial crystalline phase is changing. The high-temperature pattern corresponds to the pattern for the anhydrate found by Kawamura et al (Figure 11).…”

“…2 They also established that the commercial form was a hydrate with at most 2/3 mol of water per mol of PGS. 2 An anhydrous form was obtained by drying the hydrate for 2 h at 443 K under a vacuum. The anhydrate transforms back into the hydrate overnight at 298 K and 45% relative humidity.…”

“…3,5 According to Kawamura et al in 1987, commercially available PGS consists predominantly of potassium guaiacol-4-sulfonate. 2 They also established that the commercial form was a hydrate with at most 2/3 mol of water per mol of PGS. 2 An anhydrous form was obtained by drying the hydrate for 2 h at 443 K under a vacuum.…”

“…The anhydrate transforms back into the hydrate overnight at 298 K and 45% relative humidity. 2 Even though X-ray diffraction patterns had been used to differentiate the hydrate from the anhydrate, no crystal structure has been published for PGS. Considering that PGS is an old active pharmaceutical ingredient, the absence of a crystal structure is unexpected, not in the least because crystal structures are necessary for quality control.…”