Process Development, Formulation, and Evaluation of Water-Dispersible Granules of a New Polymorph of the Herbicide Isoxaflutole

Polymorphic stability is a critical factor in the formulation of active ingredients, influencing product performance and shelf life. In the present work, a new polymorph of the selective pre-emergence herbicide isoxaflutole (ISF) was identified by an unconventional crystallization approach, and a process to prepare the same was developed on a lab scale by various approaches. The structure of the new polymorph, namely Form II, was determined by single-crystal X-ray diffraction and further characterized by powder X-ray diffraction, and by thermal and spectroscopic methods. The process development strategy for Form II preparation was established by various approaches, and the process was finally optimized by lyophilization and spray-drying methods. The solvent selection, temperature, and concentration of the material were optimized in the process development stage. Form II was found to be unstable at room temperature. Therefore, a comprehensive solid-state stability study of Form II was conducted under various conditions, including different temperature and humidity levels, exposure to organic solvents and aqueous media, and short-term storage at room temperature. Further, to stabilize Form II, wet and dry granulation methods for producing water-dispersible granules (ISF-WDG) were employed at 40% active ingredient loading. Wet granulation induced polymorphic transformation, whereas dry granulation preserved the desired polymorph, yielding granules with acceptable wettability, flowability, and dispersibility. ISF-WDG of Form II was found to be room-temperature stable for 2 months, while pure Form II was found to be unstable and slowly converts to Form I. These findings demonstrate that dry granulation is a robust approach for stabilizing Form II. Furthermore, the aqueous solubility and release profiles were established at 25 °C and compared with those of the reported Form I. These results pave the way for further development of Form II in terms of efficacy and field-trial performance.