Abstract: In order to improve the compliance of patients with Alzheimer′s disease and maintain the continuity of treatment by reducing administration frequency of memantine hydrochloride, a series of memantine long-acting nanosuspension-based injectable formulations were prepared using a hydrophobic salt formation method. Four hydrophobic salt forms of memantine were prepared, including memantine oleate(Mem-Ole), memantine stearate(Mem-Ste), memantine palmitate(Mem-Pal)and memantine pamoate(Mem-Pam). The salt forms of memantine were characterized using fourier transform infrared(FTIR)spectroscopy, proton nuclear magnetic resonance(¹H NMR)spectroscopy and powder X-ray diffraction(PXRD)analysis. The equilibrium solubilities of different salt forms of memantine and the in vitro drug release of long-acting injectable formulations were investigated. In comparison with memantine alone, the equilibrium solubilities of Mem-Ole, Mem-Ste, Mem-Pal and Mem-Pam in simulated body fluid were decreased by 95. 1%、96. 2%、96. 7% and 99. 6%, respectively. Meanwhile, the equilibrium solubilities of Mem-Pam in simulated body fluid with pH ranging from 5 to 8 were all lower than 0. 07 mg/mL. The order of the in vitro drug release rate of the four long-acting injectable formulations with nanosuspensions of memantine was Mem-Ste> Mem-Pal≈Mem-Ole> Mem-Pam> Memantine. The Mem-Pam nanosuspensions could sustain drug release for seven days and exhibited a zero-order drug release profile(y=0. 549 9x+7. 594 2, r=0. 988 3). In conclusion, injectable Mem-Pam nanosuspensions showed desired drug release behavior and might potentially be applied in vivo for a week with a steady plasma drug concentration-time profile.