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 liq uid chromatograph was assembled to measure dissolution profiles of imm ediate 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 in jected sequentially onto an on-line liquid chromatography (LC) system for automated analysis; The STT E6 multiposition switching valve was u sed to sample up to six vessels simultaneously. After addressing issue s related to sample carry-over and between-probe variability; the auto mated system was used in a reproducible manner (RSD < 3%) to measure t he dissolution of immediate-release acetaminophen tablets and Accutrim (R) (containing 75 mg phenylpropanolamine HCl) 16h Precision Release(T M) tablets. An uneven injection time sequence was used to monitor thre e acetaminophen tablets per dissolution run using the automated system and each vessel was sampled about every 6.5 min. However, with Accutr im(R) 16 h Precision Release(TM) 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(R) tablets measured using the automated multivessel dissolution system compared well with manual and automated single-vessel dissolution systems.