Surfactant HLB
The hydrophilicity of surfactants can be measured by hydrophile and lipophile balance (HLB), HLB value is a relative value indicating the hydrophilicity of surfactants, the larger the HLB value, the stronger the hydrophilicity and the weaker the lipophilicity, the smaller the HLB value, the weaker the hydrophilicity and the stronger the lipophilicity.HLB value can be calculated by the following formula The HLB value can be calculated using the formula below:
The HLB value of a surfactant directly affects its properties and applications. In application, surfactants with different HLB values should be selected according to different application fields and objects. For example, in emulsification and decontamination, the surfactant with the appropriate HLB value is selected according to the polarity and temperature of the oil or dirt. The following table lists applications for surfactants with different HLB values.
Surfactants for use in aqueous solutions have high HLB values, and the HLB values of commonly used surfactants are shown in the chart below. Surfactants that are not miscible with water can be used in lipid formulations.
Critical Micelle Concentration
In colloid and surface chemistry, critical micellar concentration (CMC) is defined as the lowest concentration at which surfactant molecules can associate to form micelles in a solvent. Surfactants are widely used in drug discovery to improve the solubility and permeability of difficult-to-solve drugs. In aqueous solution, when the surfactant concentration is greater than its critical micelle concentration, the surfactant forms aggregates called micelles. As shown in the figure below, micelles are self-assembled structures with a hydrophobic inner core, which can immobilize drug molecules with low solubility (water solubility) inside the micelles, thus increasing solubility, and their mechanism of action is similar to that of cyclodextrins. The solubility of insoluble compounds can be linearly improved by means of micelles. In general, the higher the concentration of surfactant, the higher the solubility of the drug, but too large a quantity of surfactant has tolerance problems. For example, polysorbate 80 can cause allergic reactions when used above a certain limit. The use of surfactants can also be combined with other methods to further improve the solubility of the drug, such as adjusting the pH. unstable drugs can be made more stable by means of micelles, in which the drug molecules can be encapsulated within the micelles, thus improving the stability of the drug. However, encapsulation may also affect the pharmacokinetics of the compound, so caution is needed.
CMC is an important characterization parameter of surfactants. Before the surfactant concentration reaches CMC, the solution surface tension changes strongly with the change in surfactant concentration. After the CMC is reached, the solution surface tension remains relatively constant or changes at a lower slope. The CMC value of a surfactant in a given medium depends on temperature, pressure, and the presence and concentration of other surface-active substances and electrolytes. Micelles are formed only at temperatures above the critical micellar temperature.
There are many methods for determining the critical micelle concentration of surfactants, and the commonly used methods are surface tension method, conductivity method, dye method, turbidity method, fluorescence probe method, light scattering method, etc. However, the above methods have their limitations. The conductivity method is only suitable for measuring the CMC of ionic surfactants; the dye method requires simple equipment to measure the CMC, but the color change is not obvious enough, which affects the accuracy of the CMC measurement, and the addition of dyes may have an effect on the critical micelle concentration of the system, which may lead to erroneous results; the turbidity method is also due to the use of hydrocarbon solubles to influence the critical micelle concentration of surfactants, and the measured CMC may be affected by the addition of dyes. The turbidity method also affected the accuracy of CMC measurement due to the influence of hydrocarbon solvents on the critical micelle concentration of surfactant; the fluorescent probe method is simple to operate, has no special requirements on the system, the amount of probe is small, and the interference to the system is small, but it is necessary to prepare the benzene solution of pyrene probe, which is poisonous and cumbersome in the process of operation; the light scattering method requires that the solution to be measured is very clean, and it is subject to a lot of limiting factors.
