Simultaneously improving the mechanical properties, dissolution performance, and hygroscopicity of ibuprofen and flurbiprofen by cocrystallization with nicotinamide.

Pharmaceutical Research
Shing Fung ChowChangquan Calvin Sun

Abstract

To be fully exploitable in both formulation and manufacturing, a drug cocrystal needs to demonstrate simultaneous improvement of multiple key pharmaceutical properties over the pure drug crystal. The present work was aimed at investigating such feasibility with two model profen-nicotinamide cocrystals. Phase pure 1:1 ibuprofen-nicotinamide and flurbiprofen-nicotinamide cocrystals were prepared from solutions through rapid solvent removal using rotary evaporation,and characterized by DSC, PXRD, FTIR, phase solubility measurements, equilibrium moisture sorption analysis, dissolution testing and tabletability analysis. Temperature-composition phase diagrams constructed from DSC data for each profen and nicotinamide crystal revealed the characteristic melting point of the 1:1 cocrystal as well as the eutectic temperatures and compositions. Both cocrystals exhibited higher intrinsic dissolution rates than the corresponding profens. The cocrystals also sorbed less moisture and displayed considerably better tabletability than the individual profens and nicotinamide. Phase behaviors of 1:1 profen-nicotinamide cocrystal systems were delineated by constructing their temperature-composition phase diagrams. Cocrystallization with nicotinam...Continue Reading

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