The role of surfactants in the stabilization and release of chlorhexidine in the presence of phosphate salts

Abstract: Chlorhexidine and its salt form chlorhexidine digluconate (referred as CHX) are widely used in mouthwash to prevent dental plaque, improve gingivitis, and help to maintain oral health. Yet, CHX can cause discoloration or yellowing of teeth. To prevent or reduce the discoloration, sodium triphosphate (STPP) is frequently used. Since CHX is positively charged while STPP is negatively charged, the combination of the two can lead to precipitation and lose both benefits.

Surface tensiometer, UV-Vis spectrometer, ¹H, diffusion, & NOESY NMR are applied in the present investigation. It is found that CHX can be stabilized by small molecule surfactants in the presence of STPP and released by the addition of polymeric surfactants. When the surfactant concentration is above its critical micelle concentration (CMC) and the molar ratio of surfactant molecule to CHX is above 1, independent of the nature of the surfactant molecules, CHX is embedded inside micelles and effectively protected from interacting with STPP to form precipitates. When CHX is embedded, it could exhibit slow antibacterial action due to the slow release of CHX from the micelles. The addition of polymeric surfactants. poloxamers, induces formation of poloxamer-surfactant mixed micelles, which effectively speed-up the release of CHX molecules. The key point of using the polymeric surfactants is that the concentration needs to be below its CMC so polymeric surfactants will only form mixed micelles with small molecule surfactants but not form their own separated micelles. In the mixed micelles, the hydrophobic segment of polymeric surfactant stays in the core, which pushes CHX to the interfacial regime of the mixed micelles. Additionally, the incorporation of polymer surfactants into small molecule surfactant micelles can effectively loosen up the micelle structure and further enhance the speedy release of CHX.