Improvement of powder properties of boscalid monohydrate by a quasi-emulsion solvent diffusion-based crystallization route

Abstract

Background

The smooth production of pesticide formulation of boscalid monohydrate is restricted by its poor flowability. Here, this work develops a QESD-based crystallization route for preparing spherical agglomerate of boscalid monohydrate.

Methods

The solubility of boscalid (form II) in ethyl acetate was measured and correlated to provide reference for designing subsequent crystallization experiments. Besides, modeling work was implemented to predict the morphologies of the two solid forms of boscalid and explain the formation mechanisms. By investigating types of emulsifiers, emulsifier concentration, boscalid concentration and stirring rate, the crystallization route for producing spherical agglomerate of boscalid monohydrate was designed and optimized. Online monitoring and ¹H NMR experiments were used to study the fabrication mechanism of boscalid monohydrate spherical agglomerate.

Significant Findings

Firstly, boscalid has suitable solubility in ethyl acetate, which indicates that ethyl acetate is suitable as a good solvent in the crystallization process of boscalid. Secondly, the modeling results show that the solvent-crystal interactions composed of hydrogen bonding interaction and van der Waals interaction are affected by the roughness of the crystal face and the exposed functional groups on the crystal face. And the different solvent-crystal interactions on the four crystal faces of boscalid monohydrate make solvent molecules have different suppression influences on the growth rate of each crystal face in the ethyl acetate-water system. Thirdly, boscalid monohydrate spherical agglomerate with uniform particle size and good flowability was successfully fabricated out. Fourthly, online monitoring and ¹H NMR results confirm that the hydrogen bonding interaction between boscalid and HPMC enables the stability of emulsion droplets where boscalid monohydrate agglomerates into spherical particle. Finally, the scalability and sustainability prospects of the crystallization route have been explored.