Pharmaceutical salts preparation, counterions

Table 1 Potential counterions used in the preparation of pharmaceutical salts...

Coordination complexes with active pharmacological molecules, which comprise metallodrugs and metallopharmaceuticals, are a much less explored class of reactions. Metallodrugs, in which the metal ion is also the biologically active component, and metallopharmaceuticals, in which the metal ion plays the role of a carrier for the API molecule, similar to the counterion in a pharmaceutical salt or the coformer in a pharmaceutical cocrystal, have been successfully prepared by mechanochemistry [16]. 

Another consideration is the toxicity of the counterion. A large number of anions and cations are available for pharmaceutical compounds, and tabulations of those approved by the FDA have appeared in the literature (9,12). An expanded but not comprehensive list of acceptable ions is presented in Table 4. In general, ions related to normal metabolic chemicals or present in food or drink are usually regarded as suitable candidates for preparing salts. 

Unlike enantiomers, diastereomers have different solubilities in an achiral environment. Many chiral counterions, such as arginine and lysine, are commonly used to prepare salts of an ionic drug in order to improve its pharmaceutically relevant properties. However, when the drug is chiral, a chiral counterion should be used with caution. If the drug or the counterion is racemic, diastereomeric salts will be formed, constituting a heterogeneous system. Because the solubilities of diastereomers differ, a diastereomeric mixture of chiral salts is undesirable in a formulation. 

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