EUROPEAN CONGRESS AND EXHIBITION ON ADVANCED MATERIALS AND PROCESSES - EUROMAT 2021

Recently we showed that the ibuprofen dimer formation can cause the incomplete cocrystalization of ibuprofen and nicotinamide in course of hot melt extrusion process. Here, we extend our analysis to investigate the effect of ibuprofen degree of polymerization on ibuprofen and nicotinamide phase behavior. We used extended Flory–Huggins model combined with molecular dynamics employing a refined version of consistent valence forcefield developed from ab initio energy surfaces. Results suggest that increasing the ibuprofen degree of polymerization systematically: (1) decreases the lower and upper critical mixture temperatures and (2) moves the critical point of mixture toward higher fraction of nicotinamide, xNCTA→≈ 0.83. High fraction of nicotinamide is not desirable as it is added as coformer and not the active pharmaceutical ingredient (ibuprofen). Therefore, the ibuprofen polymerization should be avoided, and to do so, it is needed to keep the operating temperature of mixture well below the ibuprofen melting temperature i.e. 353.15K.