Hydrophobic ion pairing: altering the solubility properties of biomolecules

Pharm Res. 1998 Feb;15(2):188-93. doi: 10.1023/a:1011998014474.


The high aqueous solubility of ionic compounds can be attributed to the ease of solvation of the counter ions. Replacement of the counter ions with ionic detergents dramatically alters the solubility properties of the molecule. Not only does the aqueous solubility drop precipitously, but the solubility in organic phases increases as well. Consequently, the partition coefficient changes by orders of magnitude. This ion pairing phenomenon, which we term hydrophobic ion pairing (HIP), has been extended to polyelectrolytes, such as proteins and polynucleotides. These materials form HIP complexes that dissolve in a range of organic solvents, often with retention of native structure and enzymatic activity. The HIP process has been used to purify protein mixtures, conduct enzymatic reactions in nonaqueous environments, increase structural stability, enhance bioavailability, and prepare new dosage forms.

Publication types

  • Review

MeSH terms

  • Biological Transport
  • Dosage Forms
  • Drug Stability
  • Ions
  • Solubility*


  • Dosage Forms
  • Ions