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Mechanistic Study on Complexation-Induced Spring and Hover Dissolution Behavior of Ibuprofen-Nicotinamide Cocrystal

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journal contribution
posted on 31.10.2018, 00:00 by Yuanfeng Wei, Li Zhang, Ningning Wang, Peiya Shen, Haitao Dou, Kun Ma, Yuan Gao, Jianjun Zhang, Shuai Qian
Pharmaceutical cocrystal has gained increasing interest due to its ability to modify various physicochemical properties of hydrophobic drugs, especially solubility and dissolution. The temporarily generated supersaturation during the dissolution of cocrystals, usually called “spring and parachute” effect, would favor the oral absorption of poorly soluble drugs. In this study, biopharmaceutics classification system II drug ibuprofen (IBU) was cocrystallized with nicotinamide (NIC) by slow solvent evaporation. An AP-type complexation between IBU and NIC was observed by phase solubility study, and complexation phenomenon was verified by fluorescence quenching method. Reduction of solvation barrier by inserting extremely soluble NIC in the crystal lattice of IBU makes the cocrystal gain a 70-fold higher aqueous solubility than that of original crystalline IBU. A novel mathematic model, considering both the ionization of IBU and the complexation between IBU and NIC, was developed and well-fitted to experimental pH solubility of cocrystal. Surprisingly, instead of common spring and parachute, the prepared IBU-NIC cocrystal demonstrated an initially rapid dissolution followed by a constant high concentration, like a helicopter hovering in the sky, during its nonsink dissolution. Such a result is interpreted with a spring and hover model, which should be ascribed to the enhanced IBU solubility by complexation with the coformer NIC.