Short-Term Chronoamperometric Screening of Chlorpromazine-Package Interactions

• Published in: Journal of pharmaceutical sciences 1998-09, Vol.87 (9), p.1130-1137
• Main Authors: Sarsfilied, Beth A., Maloy, J.T.
• Format: Article
• Language: English
• Subjects: Analysis; Biological and medical sciences; Chemistry, Pharmaceutical; Chlorpromazine - chemistry; Drug Packaging; General pharmacology; Glass - chemistry; Medical sciences; Models, Chemical; Neuropharmacology; Pharmacology. Drug treatments; Plastics - chemistry; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1021/js9704700

□ 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 40μL drops of solution containing drug placed on a solid substrate disk of about 7mm diameter in a sample cell designed to accommodate a miniaturized three-electrode setup. Logarithmic current signatures obtained by computing A(ln i)/∆(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 A(ln i)/A(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.