Revealing the Effect of Additive Molecular Structure on Inducing Spherulitic Growth of L-Isoleucine

Abstract

As one of the essential amino acids, L-isoleucine, tends to crystallize in flaky crystals, yielding low bulk density and poor flowability, hindering downstream processing.While previous studies utilized hydroxypropyl methylcellulose (HPMC) to induce spherulitic growth of L-isoleucine by adsorbing onto its dominant crystal face, there is still significant potential for improvement in the bulk density and sphericity of the prepared spherulites. In this work, we systematically screened a series of amino acids (small molecules) and cellulose derivatives (polymeric molecules) as additives based on their differences in molecular functional groups. The results of scanning electron microscopy, atomic force microscopy, and specific surface area tests indicated that, under the same additive type, strong hydrophilic groups and larger molecular volumes were conducive to the roughening of the dominant hydrophilic (001) crystal face of L-isoleucine and promoted the formation of dense spherulites through the non-crystallographic branches. Molecular dynamics simulations further demonstrated that the changes in solution viscosity caused by polymeric additives also significantly affected the spherulitic growth of L-isoleucine. By rationally selecting additives, the bulk density of L-isoleucine spherulites was increased to 0.573 g/mL, which is 39.8%higher than what has been reported, and the sphericity reached 0.894. This study reveals the mechanism of the molecular structure of additives on the spherulitic growth of L-isoleucine, which is conducive to guiding the spherulite design of flaky organic molecular crystals.