Advanced Methodologies for Pharmaceutical Salt Synthesis

Pharmaceutical salt formation is the most preferred and effective method to enhance the physicochemical properties of an active pharmaceutical ingredient (API) such as solubility, bioavailability, stability, and processability. Salts are defined as crystalline materials composed of two or more different molecules, typically, drug and salt formers in the same crystal lattice, where the components in the crystal lattice are in an ionized state and interact via ionic interactions. Conventionally, the solvent-mediated process is used to manufacture the salts, where the use of a vast amount of solvent has a detrimental effect on the environment. Recently, there have been very few solvent-free methods reported for pharmaceutical salt manufacturing salt. In this article, recent trends and advances in synthesis and manufacturing of salts are reviewed. Furthermore, the operational principles of commonly employed salt manufacturing technologies are discussed including their benefits and drawbacks in terms of purity, stability, throughput, and limitations in large-scale production. The final section is devoted to reviewing the regulatory issues in terms of the patent application for the salt form of an API compared to other multicomponent forms.

Automated summary

Pharmaceutical salt formation is a preferred method to enhance the properties of an active pharmaceutical ingredient; however, the traditional solvent-mediated process has environmental concerns. Recent advancements have led to a few reported solvent-free methods for salt manufacturing. This article reviews the trends in salt synthesis and manufacturing, as well as regulatory issues related to patent applications for salt forms of APIs compared to other multicomponent forms.