Effect of additives on the kinetics of interconversion of sulphamethoxydiazine crystal forms

Abstract

Abstract The effect of various additives on the rate of transformation of the more energetic sulphamethoxydiazine Form II to the water-stable Form III in aqueous suspension has been studied. Representative structurally related compounds, viscosity imparting agents, surfactants and colouring agents have been used to inhibit the transformation. Significant transformation retarding effects were observed in most cases. The effects vary, however, from slight retardation to almost complete inhibition of the transformation for periods of over a year (e.g. using 1 % w/v of polyvinylpyrrolidone). The effect of seeding suspensions of Form II with nuclei of Form III in the presence and absence of additives has also been examined. Accelerated stability testing is shown to be inadequate for the prediction of stability of Form II in aqueous suspension in the presence of acacia or polyvinylpyrrolidone. The use of the results in the formulation of dosage forms containing sulphamethoxydiazine is suggested.