A PHYSICOCHEMICAL APPROACH TO THE INVESTIGATION OF THE STABILITY OF TRIMETHOPRIM-SULFAMETHOXAZOLE (COTRIMOXAZOLE) MIXTURES FOR INJECTABLES

The stability of the trimethoprim/sulfamethoxazole (1:5, w/w) combinat ion suitable for administration by injection was investigated to deter mine the nature of solid phases that can separate after dilution with infusion fluids. Phase-solubility analysis was performed on the binary system in water and in buffered aqueous media (pH 7 and 9), thus allo wing a comprehensive picture of solid-solution compositions. Commercia l samples of this combination were tested for solid phases separating after dilution with various infusion fluids. The interaction between t rimethoprim and sulfamethoxazole, forming a 1:1 molecular compound wit h low solubility in water, is mainly responsible for the physicochemic al properties of mixtures of these drugs in solution. Other solid phas es (i.e., trimethoprim monohydrate and sulfamethoxazole emihydrate) ca n separate on long-term standing of solutions, depending on the value of the pH of the medium and the fluid used for dilution.