cloud point

Warm a clear solution of certain nonionic surfactants and at a particular temperature it suddenly turns milky and cloudy, as if it had caught a chill in reverse. That temperature is the cloud point, and crossing it marks the surfactant beginning to fall out of solution.

Nonionic surfactants such as polysorbates and poloxamers dissolve in water by hydrogen-bonding their polyoxyethylene chains to water molecules. As temperature rises, this hydration weakens, the surfactant becomes less water-loving, its micelles swell and aggregate, and at the cloud point the solution separates into a surfactant-rich phase and a surfactant-poor phase, scattering light and turning turbid. Cooling below the cloud point usually reverses the change.

The cloud point is a practical formulation limit. Sterilising a polysorbate-stabilised product by autoclaving, or storing it warm, can push it past the cloud point, where loss of solubilising power may let a dissolved drug precipitate or an emulsion destabilise. Formulators therefore check the cloud point and may raise it with additives or choose a surfactant whose cloud point sits safely above processing and storage temperatures. The caveat is that the cloud point is shifted by salts, cosolvents, and the drug itself, so it must be measured in the actual formulation, not assumed from the raw surfactant.