Salt Stability – The Effect of pHmax on Salt to Free Base Conversion

Purpose The aim of this study was to investigate how the disproportionation process can be impacted by the properties of the salt, specifically pH max . Methods Five miconazole salts and four sertraline salts were selected for this study. The extent of conversion was quantified using Raman spectroscopy. A mathematical model was utilized to estimate the theoretical amount of conversion. Results A trend was observed that for a given series of salts of a particular basic compound (both sertraline and miconazole are bases), the extent of disproportionation increases as pH max decreases. Miconazole phosphate monohydrate and sertraline mesylate, although exhibiting significantly different pH max values (more than 2 units apart), underwent a similar extent of disproportionation, which may be attributed to the lower buffering capacity of sertraline salts. Conclusion This work shows that the disproportionation tendency can be influenced by pH max and buffering capacity and thus highlights the importance of selecting the appropriate salt form during the screening process in order to avoid salt-to-free form conversion.