Stability of pharmaceutical salts in solid oral dosage forms

Abstract

Using pharmaceutical salts in solid dosage forms can raise stability concerns, especially salt dissociation which can adversely affect the product performance. Therefore, a thorough understanding of the salt instability encountered in solid-state formulations is imperative to ensure the product quality. The present article uses the fundamental theory of acid base, ionic equilibrium, relationship of pH and solubility as a starting point to illustrate and interpret the salt formation and salt disproportionation in pharmaceutical systems. The criteria of selecting the optimal salt form and the underlying theory of salt formation and disproportionation are reviewed in detail. Factors influencing salt stability in solid dosage forms are scrutinized and discussed with the case studies. In addition, both commonly used and innovative strategies for preventing salt dissociations in formulation, on storage and during manufacturing will be suggested herein. This article will provide formulation scientists and manufacturing engineers an insight into the mechanisms of salt disproportionation and salt formation, which can help them to avoid and solve the instability issues of pharmaceutical salts in the product design.

Keywords:

• Salt disproportionation
• salt formation
• acid base interaction
• pH_max
• drug excipient compatibility

Acknowledgements

Authors would like to thank Dr. Anthony Drager and Dr. Mehran Yazdanian for helpful scientific discussions.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.