SHORT-TERM CHRONOAMPEROMETRIC SCREENING OF CHLORPROMAZINE-PACKAGE INTERACTIONS

A new electroanalytical method has been developed to measure and predi ct solute sorption interactions with solid surfaces. By maximizing sur face-to-volume ratios, this method significantly reduces the study tim e of drug-package interactions and allows prediction of possible long- term effects. Chronoamperometry experiments were run in 40 mu L 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 comp uting Delta(ln i)/Delta(ln t) were used to define the experimental con ditions necessary to avoid the kinetic complications of chlorpromazine oxidation in the interpretation of the results of the chronoamperomet ric 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 int eracts most quickly with PVC and HDPE and least with glass and polypro pylene. Long term stability tests confirmed these predictions, thereby indicating that the small volume method makes drug-package interactio n studies feasible in early development. The generation and analysis o f Delta(ln i)/Delta(ln t) signature curves extends the usefulness of t he electroanalytical method to other systems by accurately identifying the appropriate time domains for steady stale or Cottrell behavior.