Abstract
The mechanism of midazolam loss into a polyvinyl chloride (PVC) bag or an administration set was investigated in equilibrium and kinetic studies.When the buffer solution of midazolam stored in a glass or polypropylene container no drug loss was observed, but in a PVC bag the amount of midazolam remaining in the solution was reduced as storage prolonged.After 24 hrs, nearly 53.8% of midazolam was sorbed into the bag at pH 6.0. A linear relation was found between the amount of midazolam sorbed into an administration set and the equilibrium concentration of midazolam in the range of 4-20μg/ml at 30°C. The amount of midazolam sorbed into an administration set was influenced by the pH of the solution.When the midazolam concentration was 15μg/ml in aqueous solution, it was 0.45mg/g at pH 5.0 and was increased to 5.24mg/g at pH 7.0. The calculated amount of sorbed midazolam, supposing that the equilibrium sorbed amount was in proportion to the apparent partition coefficients [diethylhexyl phthalate (DEHP)/water], was in good accordance with the experimental data. We estimated that midazolam loss into a PVC bag or an administration set occurred through partition and diffusion of midazolam to DEHP used as a plasticizer of PVC.
