AUTOMATED ANALYTICAL SYSTEMS FOR DRUG DEVELOPMENT STUDIES .2. A SYSTEM FOR DISSOLUTION TESTING

Microdialysis is a non-equilibrium dynamic sampling method in which th e analytes diffuse across a semipermeable membrane due to a concentrat ion gradient and are carried away by the constantly pumping perfusion medium for on-line analysis. A BAS, Inc. microinfusion pump/injector a nd an on-line LC system were interfaced with a dissolution apparatus t o automate dissolution testing of tablets. A DL-5 microdialysis loop p robe was suspended in the dissolution medium for sampling. The automat ed system was used reproducibly (RSD <2%)to measure the dissolution of acetaminophen and Sulfatrim tablets. Drug recovery from the microdial ysis probe was a function of the perfusion rate at constant temperatur e. However, microdialysis recovery was independent of drug concentrati on over the linear ranges of the assays for the analytes of interest. Dissolution profiles determined by microdialysis sampling were compare d with manual sampling. Identical profiles were obtained for acetamino phen tablets in water at 37 degrees C and 50 rpm by both sampling meth ods. Dissolution of Sulfatrim tablets was determined in 0.1 M hydrochl oride acid at 37 degrees C and 75 rpm. Microdialysis sampling permitte d the use of a specially designed perfusion medium to buffer the acidi c samples before injecting onto the LC column. Dissolution profiles of sulphamethoxazole were comparable for both sampling methods; however, microdialysis sampling indicated slightly higher release of trimethop rim from the Sulfatrim tablets, which was attributed to release of ads orbed drug from the;connecting tubing.