About half of the drugs currently on market are salts. Salt based formulations are often preferred to those using neutral molecules, because they provide higher solubility. However, salts are prone to form hydrates, which may lead to stability problems with the drug product. The aim of this work is to investigate how specific hydrogen bonding interactions influence hydrate formation and whether the different propensities of ions towards hydrate formation  can be related to hydrogen bonding preferences.
The hydrogen bond coordination  of ammonium, chloride and carboxylate ions will be discussed using data from the Cambridge Structural Database . Comparisons between hydrate and anhydrous structures of the same ion pair reveal how water–ion hydrogen bonding competes with direct anion–cation hydrogen bonds. For example, the average coordination number of ions is larger in hydrates, but the frequency of direct anion–cation bonds is reduced in hydrates relative to anhydrates. Similarly, the average number of ammonium ions bonding to a single anion is lower in hydrates than in anhydrous structures. Analysis of the hydrogen bonding environment of water in these structures shows clear differences between the anions and cations, e.g, in ammonium carboxylate salts water–carboxylate bonds are much more frequent than ammonium– water bond.References: