Interactions between drugs and polyvinyl chloride infusion bags

Forty-six injectable drug products, many of which are administered by i.v. infusion, were studied for loss from aqueous solutions stored in polyvinyl chloride infusion bags for various periods of time. The polyvinyl bags were stored in the dark at room temperature for up to three months. Drugs stored in glass vials served as controls. The solutions were assayed spectrophotometrically at regular intervals. The effects of drug concentration and pH on the loss of drug from solution were studied. Octanol-water partition coefficients were used as a gauge of lipid solubility of the drugs. Five of the drug products-clomethiazole edisylate, diazepam, hydralazine hydrochloride, thiopental sodium, and warfarin sodium-were found to be lost to a substantial extent after one week. For all drugs studied, the effects of the initial concentration on drug loss varied. The amount of drug lost over a given time was a function of the pH of the solution. The main physico-chemical determinants controlling drug sorption appeared to be the extent of ionization and the lipid solubility of the drug. For most of the drugs studied, minimal losses from the aqueous solutions were observed over short periods of storage time. Disappearance was slow and time dependent, indicating a diffusion-controlled sorption process. The losses of clomethiazole edisylate, thiopental sodium, and diazepam may be clinically important.