Characterization of donepezil prepared by cogrinding with salicylic acid and p-aminobenzoic acid

Abstract

Two systems for the formation of cocrystals of donepezil were investigated using donepezil hydrochloride and donepezil solvate with salicylic acid and p-aminobenzoic acid. The donepezil solvate was prepared through an acidbase reaction between a hydrochloride salt and a base in methanol. Donepezil HCl (DH) and the solvate with salicylic acid and p-aminobenzoic acid (PABA) at 1:1 molar ratios were prepared using the cogrinding method. Cocrystals were characterized using attenuated total reflection-FTIR spectroscopy (ATR-FTIR), nuclear magnetic resonance spectroscopy (13 C and 1 H NMR), Powder X-ray diffraction, and differential scanning calorimetry. These results indicate that the cogrinding process could induce cocrystal formation in donepezil systems through a simple process that allows for rapid screening of cocrystals of donepezil.