Sulfamethoxazole/Trimethoprim複合体の溶解挙動とバイオアベイラビリティー

抄録

The dissolution behavior and bioavailability in man of 1 : 1 sulfamethoxazole-trimethoprim complex (STC) and its physical mixture (STM) were compared. The mean particle size of both drug powders used in this study was less than 10 μm. In the pH range of gastrointestine, no difference in solubility between STC and STM was substantially detected and the stability constant of STC in its dissolved form was less than about 19 M^-1. Furthermore STC and STM exhibited an equal dissolution rate in the pH range of less than 3, while STC showed a lower dissolution rate than STM in pH 4.5-7.5. On the other hand, no difference was found between STC and STM in fine granules as to the rate and extent of bioavailability in man. These findings lead to a conclusion that the dissolution processes of both drug powders are not rate-limiting in absorption because these particle sizes are fine enough. STC did not have a bitter taste due to trimethoprim : this may be interpreted by the fact that the concentration of trimethoprim during dissolution process of STC in a salivary pH did not reach the threshold concentration for a bitter taste. The above results showed that STC has a great advantage in formulation of the oral preparations with no bitter taste bioequivalent to STM-containing oral preparations.