Solubility enhancing reagents refers certain substances added to the system to accelerate the dissolution of the origin to be dissolved into the solvent or increase the solubility of the insoluble substance in the solvent. Commonly used solubilizers include sodium, potassium, ammonium, and sodium lower alkyl benzene sulfonate such as toluenesulfonic acid, urea, xylene sulfonic acid and cumene sulfonic acid, as well as ethanol, isopropanol, ethyl Glycol mono butyl ether, alkyl phosphate, etc.

Solubilization effects:

The solubilization effects of common solubility enhancing reagents include complexation, association, latent solubilization and solubilization of surfactants.

• Complexation: Complexation is a separation method based on the interaction between the Lewis acid (or base) functional group of the solute and the Lewis base (or acid) functional group of the complexing agent. By reacting with the complexing agent to form a complex, the substance to be separated can effectively enter into the solvent. Because the chemical bond energy produced by complexation is small, the complexing agent can be re-separated and recovered during reverse extraction, so this method has the advantages of high selectivity and high efficiency, and both complexing agent and solvent can be recovered. Taking the separation of carbon monoxide by complexation as an example, the separation of carbon monoxide by complex absorption is a reversible reaction and belongs to chemical absorption. At room temperature, cuprous aluminum tetrachloride toluene forms a complex with carbon monoxide to separate the carbon monoxide from other gases that do not form a complex with cuprous aluminum tetrachloride toluene, and then release carbon monoxide by heating. At the same time, the uncomplexed cuprous aluminum tetrachloride toluene can continue to be used.
• Association: Association refers to the reversible binding between homologous or different molecules that does not cause changes in chemical properties, and the formation of hydrogen bonds between molecules is the main reason for the association. At present, most researchesd ionic association complexes are mainly formed by the combination of metal coordination ions and hydroelectric ions through electrostatic interaction. Taking the extraction and separation of zirconium and hafnium with tributyl phosphate as an example, the tributyl phosphate coordinates with metal atoms through the oxygen atom on the－P=O bond to form a neutral extract.

Figure 1. Tributyl phosphate.

• Latent solubilization: The latent solubilization effect is mainly based on the principle that different solvents have a special affinity for drug molecules of different structures, so that the solubility of drugs reaches the maximum in the mixture containing a certain proportion of different solvents. The latent solution mainly achieves maximum solubility by adjusting the characteristic parameters related to the solubility of the mixed solvent, such as dielectric constant, surface tension, partition coefficient and so on, but it still follows the principle of "similar miscibility".
• Solubilization of surfactants: The solubilization of surfactants means that under the action of surfactants, the solubility of substances that are incompatible or poorly soluble with solvents can be significantly increased. For example, nonionic surfactants, such as polysorbate 20, Poloxamer 188 and polyethylene glycol 400, have good solubilization effects on three insoluble components including baicalin, cholic acid and porcine deoxycholic acid in different solvents.

Figure 2. Polysorbate.

References:

1. Zhao Guoxi, Zhu Buyao. (2003) "The principle of surfactant action." Daily Chemical Industry Information. (17): 16-16.
2. Jin Yunfeng, Liu Ruixin.(2016) "Comparison of solubilization effects of insoluble ingredients." China Modern Chinese Medicine. 18(2): 213-218.