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.

The effect of initial precipitates on the induction period of l-ornithine-l-aspartate during semi-batch drowning out crystallization

“…As pointed out earlier, we previously investigated pseudopolymorphism of LOLA crystallization [6]. The crystal form depended not only on the operating temperature but also on the feeding conditions.…”

“…The experimental setup and procedure are detailed elsewhere [6,7]. LOLA (C 5 H 13 N 3 O 2 + Á C 4 H 6 NO 4 À , MW 265.3, Sigma) was used after drying for 12 h in a vacuum oven kept at 50 1C.…”

“…We previously reported that the anhydrous form of Lornithine-L-aspartate (LOLA), which has also hydrous form, could be obtained by drowning out by adding an aqueous LOLA solution to an antisolvent, methanol [5,6].…”

“…Molecular ions of L-ornithine and L-aspartic acid carry a positive charge and a negative charge in water, respectively. The previous study was concerned about theoretical solubility description in electrolyte solution, controlling the polymorphs, the size of agglomerates and impurities in spherical agglomeration process [5][6][7].…”

Computational fluid dynamics modeling of mixing effects for crystallization in coaxial nozzles

“…The polymorphic or pseudopolymorphic form can also depend on the operating conditions [32][33][34][35][36][37].…”