Global InformationHydrotrope information
A hydrotrope is a compound that solubilizes hydrophobic compounds in aqueous solutions by means other than micellar solubilization. Typically, hydrotropes consist of a hydrophilic part and a hydrophobic part (similar to surfactants), but the hydrophobic part is generally too small to cause spontaneous self-aggregation. Hydrotropes do not have a critical concentration above which self-aggregation spontaneously starts to occur (as found for micelle- and vesicle-forming surfactants, which have a critical micelle concentration (cmc) and a critical vesicle concentration (cvc)). Instead, some hydrotropes aggregate in a step-wise self-aggregation process, gradually increasing aggregation size. However, many hydrotropes do not seem to self-aggregate at all, unless a solubilizate has been added. Examples of hydrotropes include urea, tosylate, cumenesulfonate and xylenesulfonate.
The term hydrotropy was originally put forward by Carl Neuberg[1][2] to describe the increase in the solubility of a solute by the addition of fairly high concentrations of alkali metal salts of various organic acids. However, the term has been used in the literature to designate non-micelle-forming substances, either liquids or solids, capable of solubilizing insoluble compounds.
The chemical structure of the conventional Neuberg's hydrotropic salts (proto-type, sodium benzoate) consists generally of two essential parts, an anionic group and a hydrophobic aromatic ring or ring system. The anionic group is involved in bringing about high aqueous solubility, which is a prerequisite for a hydrotropic substance. The type of anion or metal ion appeared to have a minor effect on the phenomenon.[1] On the other hand, planarity of the hydrophobic part has been emphasized as an important factor in the mechanism of hydrotropic solubilization[3][4]
To form a hydrotrope, an aromatic hydrocarbon solvent is sulfonated, creating an aromatic sulfonic acid. It is then neutralized with a base.[5]
Additives may either increase or decrease the solubility of a solute in a given solvent. These salts that increase solubility are said to "salt in" the solute and those salts that decrease the solubility "salt out" the solute. The effect of an additive depends very much on the influence it has on the structure of water or its ability to compete with the solvent water molecules.[6] A convenient quantitation of the effect of a solute additive on the solubility of another solute may be obtained by the Setschetow equation:[7]
- ,
where
- S0 is the solubility in the absence of the additive
- S is the solubility in the presence of the additive
- Ca is the concentration of the additive
- K is the salting coefficient, which is a measure of the sensitivity of the activity coefficient of the solute towards the salt.
- ^ a b Neuberg, C (1916). "Hydrotropic phenomena. I". Biochem. Z. 76: 107–76.
- ^ Mehringer, Johannes; Kunz, Werner (August 2021). "Carl Neuberg's hydrotropic appearances (1916)". Advances in Colloid and Interface Science. 294: 102476. doi:10.1016/j.cis.2021.102476. PMID 34229180. S2CID 235757195.
- ^ Evstigneev, M.P.; Evstigneev, V.P.; Hernandez Santiago, A.A.; Davies, David B. (2006). "Effect of a mixture of caffeine and nicotinamide on the solubility of vitamin (B2) in aqueous solution" (PDF). European Journal of Pharmaceutical Sciences. 28 (1–2): 59–66. doi:10.1016/j.ejps.2005.12.010. PMID 16483751. S2CID 24920111.
- ^ Suzuki, H.; Sunada, H. (1998). "Mechanistic studies on hydrotropic solubilization of nifedipine in nicotinamide solution". Chemical & Pharmaceutical Bulletin. 46 (1): 125–130. doi:10.1248/cpb.46.125. PMID 9468644.
- ^ Stanton, Kathleen; Caritas Tibazarwa; Hans Certa; William Greggs; Donna Hillebold; Lela Jovanovich; Daniel Woltering; Richard Sedlak (2010). "Environmental Risk Assessment of Hydrotropes in the United States, Europe, and Australia". Integrated Environmental Assessment and Management. 6 (1): 155–163. doi:10.1897/IEAM_2009-019.1. PMID 19558203. S2CID 11467860.
- ^ Da Silva, R.C.; Spitzer, M.; Da Silva, L.H.M.; Loh, W. (1999). "Investigations on the mechanism of aqueous solubility increase caused by some hydrotropes". Thermochimica Acta. 328 (1–2): 161–167. doi:10.1016/s0040-6031(98)00637-6.
- ^ Singhai, A., 1992. Studies on solubilization, formulation and evaluation of some drugs, Dept. of Pharm. Sci. Dr. H. S. Gaur vishwavidhyalaya., Sagar, 10.