ABSTRACT
It has been estimated that 40% of new drug molecules suffer from poor aqueous solubility. In polar compounds, low solubility may be due to strong intermolecular electrostatic attraction and/or hydrogen bonding, while the low aqueous solubility of hydrophobic and lipophilic compounds is usually attributed to an unfavorable free energy of solvation by water. In the case of hydrophobic compounds, these may additionally be poorly soluble in oils, which may make formulation much more challenging than for lipophilic compounds, which may be solubilized by oily vehicles. If a drug molecule possesses an ionizable group, one way of improving the aqueous solubility of polar, hydrophobic, or lipophilic compounds is by salt formation. In some cases such as in taste masking, for controlled release, to improve chemical stability, or lymphatic targeting, it may be desirable to decrease the aqueous solubility. Judicious choice of the proper counterion can help accomplish these goals.
