Automated analytical systems for drug development studies. 3. Multivessel dissolution testing system based on microdialysis sampling.

An automated system consisting of a six-vessel dissolution apparatus, microdialysis sampling, STT E6 multiposition switching valve and a liquid chromatograph was assembled to measure dissolution profiles of immediate and sustained-release tablets. A DL-5 microdialysis loop probe (BAS, Inc.) was immersed in each dissolution vessel and perfused with a suitable medium for sampling. The dialystate from each vessel was injected sequentially onto an on-line liquid chromatography (LC) system for automated analysis. The STT E6 multiposition switching valve was used to sample up to six vessels simultaneously. After addressing issues related to sample carry-over and between-probe variability, the automated system was used in a reproducible manner (RSD < 3%) to measure the dissolution of immediate-release acetaminophen tablets and Accutrim (containing 75 mg phenylpropanolamine HCl) 16 h Precision Release tablets. An uneven injection time sequence was used to monitor three acetaminophen tablets per dissolution run using the automated system and each vessel was sampled about every 6.5 min. However, with Accutrim 16 h Precision Release tablets, a longer sampling interval (10 min) was used, the six tablets could be tested in each dissolution run. The dissolution profiles of acetaminophen and Accutrim tablets measured using the automated multivessel dissolution system compared well with manual and automated single-vessel dissolution systems.