Influence of Seed Properties and Operating Conditions on Secondary Nucleation of Glyphosate

Secondary nucleation critically governs crystal size distribution (CSD), yet its precise control remains challenging. Here, in situ process analytical technologies (PAT) were used to investigate the secondary nucleation of glyphosate. A method based on a defined nucleation core-interval was established to determine the average secondary nucleation rate, enabling quantitative assessment of seed size, seed loading, seed shape, cooling rate, and agitation rate. To clarify morphology effects, an additive-free approach combining isoelectric-point and cooling crystallization was developed to prepare spheroidized seeds. Under identical size conditions, spheroidized seeds markedly suppressed secondary nucleation relative to prismatic seeds, yielding larger and narrower crystals. Thus, a seed-shape factor was incorporated into the averaged secondary nucleation model, improving performance (R2: 0.54 to 0.95; ARD: 49.94% to 18.51%) and yielding more physically consistent exponents. These results highlight seed shape as a key regulator of secondary nucleation kinetics and offer an effective pathway for tailoring CSD.