Simultaneous control of polymorphism and morphology via gelatin induction for concomitant systems: case study of sulfathiazole

Abstract

Controlling the solid-state properties is particularly important in the pharmaceutical field, where polymorphism and morphology have a significant impact on drug properties. Sulfathiazole (ST) is a highly and concomitantly polymorphic model system. We found that pure form II cauliflower-like ST spherulites can be obtained by cooling crystallization by only adjusting the gelatin concentration in water. The ST polymorphism and morphology were characterized by PXRD, Raman and SEM. The results showed that the gelatin additive (≥0.02 g per 100 g H₂O) exhibited high selectivity to ST form II. We investigated the evolution of ST morphology by varying the gelatin concentration and initial supersaturation. The gelatin additive had the effect of inducing branching and inhibiting nucleation and growth, and promoted the formation of cauliflower-like spherulites. The mechanism for simultaneous control of polymorphism and morphology via gelatin induction was proposed, and the gelatin concentration was a dominant factor in this system. These findings provide new strategies for understanding polymorphic nucleation pathways and inducing organic spherulites.