Physicochemical Studies of Triclosan to aid Understanding of its Physiological and Environmental Effects

Methods The pKa of Triclosan was measured by a UV‐metric technique, with sample introduced as an aliquot of stock solution. The log P (octanol‐water) and aqueous solubility were measured by pH‐metric techniques, with sample introduced as a weighed powder. Material precipitating during the solubility assays was studied by polarised light microscopy. Biphasic dissolution was performed in stirred aqueous buffer with a layer of immiscible solvent (hexadecane or nonanol) floating on top. The pH was held at 1.9 for 30 minutes and then raised stepwise to 7.3, 9.5 and 11.8 and held for 30 minutes at each pH. Samples were introduced as tablets (3 mm diameter) pressed from Triclosan and held in the solvent layer during the experiment. Weights dissolved were determined from UV spectra measured in each phase by dip probes connected to spectrophotometers. Results pKa: 8.06 (25°C, 0.15 M ionic strength); log P: neutral 4.45, anion 1.38; During solubility measurement, initial precipitation was liquid‐liquid phase separation (LLPS); crystallization subsequently occurred. Solubility: LLPS 37.4 μg/mL, crystalline 25.2 μg/mL. During biphasic dissolution, Triclosan dissolved rapidly in solvents at pH 1.9 and 7.3 and none was detected in the aqueous phase. In the presence of hexadecane, the weight in the aqueous phase increased slowly at pH 9.5 and rapidly at pH 11.8, the tablet was still dissolving and both phases were clear. In the presence of nonanol at high pH the nonanol phase became cloudy and the weight increase in the aqueous phase was small. Hexadecane has no capacity to hold anions in solution at high pH, thus forcing Triclosan to partition into the aqueous phase. Nonanol is a polar solvent and has the capacity to hold on to charged anions.