Pseudopolymorphic crystallization of L-ornithine-L-aspartate by drowning out

Abstract

Crystallization of L-ornithine-L-aspartate (LOLA) by drowning out was investigated using methanol as an antisolvent for the production of the anhydrous form of LOLA. An initial mixing method of the LOLA aqueous solution with methanol was found to be a critical factor in the pseudopolymorphic crystallization of LOLA. When methanol was added into the LOLA aqueous solution, it was found that the crystal structure of LOLA was mainly determined by the operating temperature. At a temperature higher than about 60 °C, the anhydrous form of LOLA was always formed. However, at a temperature lower than 50 °C, only LOLA hydrate was produced. On the other hand, when the LOLA aqueous solution was added into methanol, the anhydrous form was obtained by controlling the operational temperature, the feeding rate of the LOLA aqueous solution, and the methanol concentration even at a temperature lower than 50 °C.