Abstract: The aim of this study is to investigate the effect of nicotinamide (NIC) on the solubility/dissolution of a poorly soluble drug ibuprofen (IBU), and to explore the mechanism of the formed soluble complex by complexation model, fluorescence quenching and Raman spectroscope. The results showed that NIC could significantly improve the solubility of IBU, and exhibited an A_p type complexation profile. The calculated complexation constants of K_1:1 and K_1:2 were 0.24 and 4.00, respectively. In the solution, the fluorescent intensity of IBU gradually decreased with the increase of NIC, exhibiting the typical fluorescence-quenching phenomenon. The Raman spectrum showed stretching vibrations, bending vibrations, and rocking vibrations ascribed to benzene ring of IBU and pyridine ring of NIC disappeared or significantly shifted, suggested that the soluble complex was formed by dipole-dipole interaction force between the benzene group on IBU and pyridine group on NIC, resulting in the aqueous solubility enhancement of IBU. In comparison to IBU alone, the physical mixture of IBU and NIC showed significantly higher dissolution rate (1.6-fold) and extent.