Succinylsulfathiazole crystal forms. III: Crystal growth studies

Abstract

Crystal growth accompanying the transformation of succinylsulfathiazole crystal forms in aqueous suspensions was studied using a projecting microscope. The effects of increase of temperature, agitation, inclusion of seeds of Form II (the water-stable dihydrate), sulfathiazole, methylcellulose, and polysorbate 80 on the particle-size distribution of anhydrous succinylsulfathiazole Form I were examined. Rates of crystal growth, calculated as increase of diameter per unit time, were given under different experimental conditions. Increase of temperature, agitation, and seeding with nuclei of Form II had significant growth-accelerating effects. Sulfathiazole and polysorbate 80 had growth-retarding effects. Methylcellulose inhibited the crystal growth of Form I for over a year. Aqueous suspensions of Form II did not show any change in particle-size distribution. The crystal growth was shown to be a direct consequence of the transformation of the crystal form. Physical conditions and additives which had accelerating or retarding effects on the rate of succinylsulfathiazole in aqueous suspensions.