Automated dissolution testing of combination drug product using high-pressure liquid chromatography.

An automated high-pressure liquid chromatographic (HPLC) system compatible with any standard tablet dissolution apparatus was developed. This system allowed the individual drug concentrations within a product to be determined simultaneously, even when the drugs had similar structures and UV spectra. This automated system permitted unattended sampling and concentration determination at predetermined time intervals. The dissolution medium was pumped continuously through a fixed-volume, microprocessor-controlled injector and returned to the USP rotating-basket dissolution apparatus. No corrections for the changing dissolution medium volume were necessary since each injection onto a reversed-phase HPLC column consumed just 10 microliter of medium. Dissolution tests were performed on three brands of trisulfapyrimidines tablets. Sample injections were made automatically at 5.1-min intervals for approximately 2 hr. Dissolution profiles were determined for each drug in each product. Statistically significant differences were found in the mean concentration-time values between drugs within a drug product and between the drug products.