Sunday, March 3, 2013


USP/NF Relative Terms of Solubility

General Rule of Solubility*
  1. Inorganic Molecules
  • If both the cation and anion of an ionic compound are monovalent, the solute-solute attractive forces are usually easily overcome, and therefore, these compounds are generally water soluble. (E.g. Sodium Chloride, Lithium Bromide, Potassium Iodide, Ammonium Nitrate, Sodium Nitrite)
  • If only one of the two ions in an ionic compound is monovalent, the solute-solute interaction are also usually easily overcome and the compounds are generally water soluble. (E.g. Barium Chloride, Magnesium Iodide, Sodium Sulfate, Sodium Phosphate)
  • If both the cation and anion are multivalent, the solute-solute interaction may be too great to overcome by the solute-solvent interaction and the compound may have poor water solubility. (E.g. Calcium Sulfate, Barium Sulfate, Bismuth Phosphate; Except Zinc Sulfate, Ferrous Sulfate)
  • Common salts of alkali metals (Na, K, Li, Cs, Rb) are usually water soluble. (Except Lithium Carbonate)
  • Ammonium and quaternary ammonium salts are water soluble.
  • Nitrates, nitrites, acetates, chlorates and lactates are generally water soluble, except silver and mercurous acetate.
  • Sulfates, sulfites, and thiosulfates are generally water soluble, except calcium and barium salts.
  • Chlorides, bromides, and iodides are generally water soluble, except silver and mercurous ions.
  • Acid salts corresponding to an insoluble salt will be more water soluble than the original salt.
  • Hydroxides and oxides of compounds other than alkali metal cations and the ammonium ion are generally water insoluble.
  • Sulfides are water insoluble except for their alkali metal salts.
  • Phosphates, carbonates, silicates, borates, and hypochlorites are wate insoluble, except for their alkali metal salts and ammonium salts.
  1. Organic Molecules
  • Molecules having one polar functional group are usually soluble to total chain lengths of five carbons.
  • Molecules having branched chains are more soluble than the corresponding straight-chain compound.
  • Water insolubility decreases with an increase in molecular weight.
  • Increased structural similarity between solute and solvent is accompanied by increased solubility.

*Based on Ansel, H., et al: Pharmaceutical Dosage Forms and Drug Delivery Systems, Sixth Edition,1995