The multiple stages towards crystal formation of L-glutamic acid

Abstract Governing polymorph selection is a crucial issue in the pharmaceutical, food, and fine chemical industry. However, the multiple stages during the formation of the polymorphic crystals from solution and the concurrent processes selecting the final polymorph are still unclear. In this study, we demonstrate the existence of hydrated amorphous intermediates in the early stages of separation of organic crystal L-glutamic acid where the nucleation of crystalline metastable α-form spontaneously occurred within these intermediates, leading to the formation of odd-shaped and intergrown crystal aggregates. Further, we found that these amorphous intermediates severed not only as a transient intermediate in a nucleation process, but they also co-determined the size distribution, mean particle size, and phase transformation rates of polymorphic L-glutamic acid.