Online monitoring of dissolution tests using dedicated potentiometric sensors in biorelevant media

The performance of the Ion-Selective Electrode (ISE) for in vitro dissolution testing using biorelevant media was evaluated in this study. In vitro dissolution was carried out using USP apparatus 2 (paddle method) with classical and with updated biorelevant media to simulate the pre- and postprandial states. The ISE was used as an analytical stand-alone system and in combination with a single-point HPLC–UV measurement. A modified method enabling the use of the ISE for very poorly soluble substances is also proposed.In terms of f2-factor, the results acquired using the ISE for the drug diphenhydramine-HCl were found to be very similar to the results obtained by manual sampling followed by HPLC–UV analysis. In Fed State Simulated Gastric Fluid (FeSSGF), a medium containing 50% milk, the ISE is more practical since the need to separate proteins from the analyte prior to HPLC–UV analysis is eliminated. Further work will be needed to establish ISE methodology for Fed State Simulated Intestinal Fluid (FeSSIF) media.In summary, the ISE has promise as an analytical tool for research and development applications.

Graphical abstractAn Ion-selective Electrode is set into a standard dissolution vessel (USP II apparatus). The electrode monitors the dissolution of a tablet by detecting changes in the electrochemical potential of the dissolution medium caused by the dissolving drug. These changes, measured in mV, are converted via a dedicated software (“Potential to Concentration”) into the concentration in % of dissolved drug. The results are compared to manual sampling with subsequent sample analysis using HPLC-UV. The results using analysis via the Ion Selective electrode are comparable to those with the conventional sample preparation.Figure optionsDownload full-size imageDownload as PowerPoint slide