Demonstration of purification of a pharmaceutical intermediate via organic solvent nanofiltration in the presence of acid

• Purification of an API intermediate via Organic solvent nanofiltration.
• Change in the rejection profile on addition of an acid.
• The type and quantity of acid was investigated.
• The requirement for some water in the solvent was shown.
• Effect of aqueous acid on membrane stability.

During the investigation into the possibility of purifying an API intermediate from a dimeric impurity via organic solvent nanofiltration (OSN). A change in rejection profile was noted on the addition of a strong acid to a solution of the amine in the mixed solvent system of tetrahydrofuran–water (80:20). This change in rejection did not occur with the impurity, thus making the separation via OSN far more effective. The requirement of all three components i.e. acid, organic solvent and water to achieve this change in rejection was also demonstrated. Additionally the type of acid, quantity and the effects of the acidic solution on membrane stability were also examined.