The influence of pH on the dissolution rates and solubilities of sulphamethoxazole and trimethoprim have been examined. Sulphamethoxazole was evaluated in buffers of ionic strength 0.5 mol dm-3 over the pH range 0.45-7.8 and at 25, 32 and 37 degrees C. The minimum solubility of sulphamethoxazole was 28.1 mg/100 mL at pH 3.22 and 25 degrees C. Solubilities increased significantly with both increased and decreased pH. Intrinsic dissolution rates demonstrated a linear relationship with the solubility data. Trimethoprim solubility was both buffer- and pH-dependent. In both water and hydrochloric acid solution at 32 degrees C the solubility of trimethoprim increased from 50 mg/100 mL in water at pH 8.54 to a maximum of 1550 mg/100 mL at pH 5.5. This maximum solubility was in excess of that predicted theoretically and may be due to supersaturation. Below pH 2 the solubility of protonated trimethoprim diminished from 1125 mg/100 mL with decreasing pH. This was due to the common ion effect. Intrinsic dissolution rates increased as pH was decreased with hydrochloric acid from 6.00 to 1.78, but decreased at pH 1.48 due to the common ion effect. Dissolution profiles of trimethoprim showed complex patterns dependent upon pH. The profile was zero-order at pH 6.00 and became distinctly stepwise at pH 5.5, this effect becoming less pronounced at lower pH values. This was reconciled in terms of the rate of formation of trimethoprim hydrochloride on the surface of the disc and the differing dissolution rates of this species and trimethoprim. A simple relationship between solubility and dissolution rate was not observed.

Dissolution rates of trimethoprim and sulphamethoxazole from combination Sulphamethoxazole showed a more variable release pattern and faster