Short-term chronoamperometric screening of chlorpromazine-package interactions

A new electroanalytical method has been developed to measure and predict solute sorption interactions with solid surfaces. By maximizing surface-to-volume ratios, this method significantly reduces the study time of drug-package interactions and allows prediction of possible long-term effects. Chronoamperometry experiments were run in 40 microL drops of solution containing drug placed on a solid substrate disk of about 7 mm diameter in a sample cell designed to accommodate a miniaturized three-electrode setup. Logarithmic current signatures obtained by computing Delta(ln i)/Delta(ln t) were used to define the experimental conditions necessary to avoid the kinetic complications of chlorpromazine oxidation in the interpretation of the results of the chronoamperometric analysis. Results of sorption studies of chlorpromazine to glass, polypropylene, high density polyethylene, poly(ethylene terephthalate), ethylene vinyl acetate, and poly(vinyl chloride) are presented. The small volume sorption experiments demonstrated that chlorpromazine interacts most quickly with PVC and HDPE and least with glass and polypropylene. Long term stability tests confirmed these predictions, thereby indicating that the small volume method makes drug-package interaction studies feasible in early development. The generation and analysis of Delta(ln i)/Delta(ln t) signature curves extends the usefulness of the electroanalytical method to other systems by accurately identifying the appropriate time domains for steady state or Cottrell behavior.