(200y) Manipulation of Crystal Morphology of Zoxamide Based on Phase Diagram and Crystal Structure Analysis

For many compounds, small needle crystals could be easily formed and crystals with other morphologies are quite difficult to be obtained by simple crystallization method, which will result in difficulties for downstream processing . To improve the properties of the solid state product, such as flowability, compressibility and son on, new crystallization technology need to be developed and designed. In this work, the manipulation of morphology and size distribution of the crystalline product was investigated by using zoxamide as model compound. Reasons for the stubborn appearance of small needle zoxamide crystals in various solvents were explained from the intermolecular interaction by analyzing the crystal structure data. Although spherical products obtained from spherical agglomeration have been discussed in literature, ellipsoidal agglomerates are rarely mentioned. In this work, ellipsoidal zoxamide agglomerates were crystallized from acetone-water-(n-hexane) solvent system and showed significantly improved flowability and compressibility. The formation mechanism of zoxamide agglomerates was investigated and discussed. Besides, the influence of bridging liquid amount, stirring speed and slurry density on the size and circularity of zoxamide agglomerates were also discussed.