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Review
, 23 (7)

Salts of Therapeutic Agents: Chemical, Physicochemical, and Biological Considerations

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Review

Salts of Therapeutic Agents: Chemical, Physicochemical, and Biological Considerations

Deepak Gupta et al. Molecules.

Abstract

The physicochemical and biological properties of active pharmaceutical ingredients (APIs) are greatly affected by their salt forms. The choice of a particular salt formulation is based on numerous factors such as API chemistry, intended dosage form, pharmacokinetics, and pharmacodynamics. The appropriate salt can improve the overall therapeutic and pharmaceutical effects of an API. However, the incorrect salt form can have the opposite effect, and can be quite detrimental for overall drug development. This review summarizes several criteria for choosing the appropriate salt forms, along with the effects of salt forms on the pharmaceutical properties of APIs. In addition to a comprehensive review of the selection criteria, this review also gives a brief historic perspective of the salt selection processes.

Keywords: chemistry; degradation; physicochemical; routes of administration; salt; stability; water solubility.

Conflict of interest statement

The authors declare no conflicts of interest

Figures

Figure 1
Figure 1
Degradation reaction of amlodipine in the presence of maleic acid.
Figure 2
Figure 2
Free base and salt form of CGP6085.
Figure 3
Figure 3
Salts of imipramine.
Figure 4
Figure 4
Various factors affecting the salt selection process.

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References

    1. Paulekuhn G.S., Dressman J.B., Saal C. Trends in active pharmaceutical ingredient salt selection based on analysis of the orange book database. J. Med. Chem. 2007;50:6665–6672. doi: 10.1021/jm701032y. - DOI - PubMed
    1. Prohotsky D.L., Zhao F. A survey of top 200 drugs—Inconsistent practice of drug strength expression for drugs containing salt forms. J. Pharm. Sci. 2012;101:1–6. doi: 10.1002/jps.22735. - DOI - PubMed
    1. Rubino J.T. Solubilities and solid state properties of the sodium salts of drugs. J. Pharm. Sci. 1989;78:485–489. doi: 10.1002/jps.2600780614. - DOI - PubMed
    1. Thomas E., Rubino J. Solubility, melting point and salting-out relationships in a group of secondary amine hydrochloride salts. Int. J. Pharm. 1996;130:179–185. doi: 10.1016/0378-5173(95)04269-5. - DOI
    1. Chowhan Z.T. Ph-solubility profiles or organic carboxylic acids and their salts. J. Pharm. Sci. 1978;67:1257–1260. doi: 10.1002/jps.2600670918. - DOI - PubMed
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