A novel process, sequential coupled‐batch diastereomeric crystallization is presented for the resolution of racemic mixtures. This strategy utilized a preferential crystallization of diastereomeric salt followed by sequential coupled diastereomeric salt resolution of racemic ibuprofen with the resolving agent (S)‐lysine utilizing a novel small scale pneumatic liquid exchange design to couple two batch crystallizers. Results were compared to conventional sequential resolution via seeded isothermal batch crystallization. Diastereomeric salt resolution was developed using the ternary phase diagram of the isolated (R)‐ibuprofen‐(S)‐lysine and (S)‐ibuprofen‐(S)‐lysine salts and optimized empirically with the aid of process analytical technology. Sequential coupled‐batch crystallization was found to be capable of increasing the yield of both salts while maintaining purity. This gave an increase in both the productivity and yield (20.5% for (S)‐ibuprofen‐(S)‐lysine) compared to the equivalent sequential batch (17.7% for (S)‐ibuprofen‐(S)‐lysine) crystallization methodology. Single crystals of the (S)‐ibuprofen‐(S)‐lysine were isolated, and its single crystal structure determined. © 2018 American Institute of Chemical Engineers AIChE J, 65: 604–616, 2019
Numerous pharmaceutical ingredients are chiral and generally only one isomer shows the desired therapeutic activity. Therefore, enantioseparation, e.g., by crystallization, is a key step in the pharmaceutical industry. In this work, ternary phase diagrams of the diastereomeric salt formation of ibuprofen lysine in aqueous ethanol are generated. The solubilities of the formed diastereomeric salts are measured in a defined temperature range. Investigation of the X‐ray powder diffraction patterns confirmed ibuprofen lysine as a simple eutectic system in agreement to the previously reported observations. The metastable zone widths of diastereomeric salt pairs of ibuprofen lysine are discussed with a resolution procedure proposed using the phase diagram that achieves maximum possible yield.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
334 Leonard St
Brooklyn, NY 11211
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.