Cocrystallization Enhanced TAK-441 Aqueous Solubility and Suppressed High Solvatomorphism

TAK-441 was cocrystallized to enhance its aqueous solubility and suppress its high solvatomorphism. A TAK-441/l-malic acid (2:1) cocrystal and a TAK-441/l-tartaric acid (2:1) cocrystal were observed, and they exhibited isomorphism. These cocrystals were 2–3 times more soluble than its free form in aqueous solutions and directly crystallized without solvate formation in various organic solvents. The cocrystals were chemically and physically stable under stress conditions and are predicted to have sufficient stability to ensure an adequate shelf life. The results demonstrated that the cocrystals had a more preferable pharmaceutical profile and that cocrystallization can both improve oral bioavailability and simplify crystal form control simultaneously.