Loss of nitroglycerin from aqueous solution into plastic intravenous delivery systems.

The mechanism of potential loss of nitroglycerin stored in plastic and glass containers was studied from an equilibrium and kinetic approach. Plastic strips equilibrated with dilute aqueous solutions of neat nitroglycerin showed that the drug was lost by absorption. Drug loss was followed by an electron-capture GLC assay. The same assay of control solutions in glass showed no drug loss in 48 hr at pH 5.7. The kinetics of nitroglycerin absorption and desorption were determined using synthesized 14C-labeled drug. Absorption can be quantified using a diffusion model, where the concentration in the aqueous phase falls with time. Curve fitting yielded an average diffusion coefficient in plastic of 2.05 x 10(-9) cm2/sec and a partition coefficient of 104 (plastic-water) at 30 degrees. Temperature-dependence studies of absorption showed that the diffusion coefficient followed an Arrhenius relationship with an energy requirement of 19.6 kcal/mole, whereas effects on the partition coefficient were negligible. Nitroglycerin desorption from plastic disks under sink conditions into water can be quantified by assuming a diffusion model where the concentration at the surface of a plane sheet remains constant. Nonlinear least-squares curve fitting generated a diffusion coefficient of 1.14 x 10(-9) cm2/sec for the desorption process at 30 degrees.