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Automated analytical systems for drug development studies. II--A system for dissolution testing.

K P Shah·M Chang·C M Riley
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Abstract

Microdialysis is a non-equilibrium dynamic sampling method in which the analytes diffuse across a semipermeable membrane due to a concentration gradient and are carried away by the constantly pumping perfusion medium for on-line analysis. A BAS, Inc. microinfusion pump/injector and an on-line LC system were interfaced with a dissolution apparatus to automate dissolution testing of tablets. A DL-5 microdialysis loop probe was suspended in the dissolution medium for sampling. The automated system was used reproducibly (RSD < 2%) to measure the dissolution of acetaminophen and Sulfatrim tablets. Drug recovery from the microdialysis probe was a function of the perfusion rate at constant temperature. However, microdialysis recovery was independent of drug concentration over the linear ranges of the assays for the analytes of interest. Dissolution profiles determined by microdialysis sampling were compared with manual sampling. Identical profiles were obtained for acetaminophen tablets in water at 37 degrees C and 50 rpm by both sampling methods. Dissolution of Sulfatrim tablets was determined in 0.1 M hydrochloride acid at 37 degrees C and 75 rpm. Microdialysis sampling permitted the use of a specially designed perfusion medium to buffer the acidic 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 trimethoprim from the Sulfatrim tablets, which was attributed to release of adsorbed drug from the connecting tubing.

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AcetaminophenDrug Evaluation, PreclinicalMicrodialysisSolubilitySulfamethoxazoleTrimethoprimTrimethoprim, Sulfamethoxazole Drug CombinationJournal ArticleResearch Support, Non-U.S. Gov't

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K P Shah, M Chang, C M Riley. 1994. Automated analytical systems for drug development studies. II--A system for dissolution testing.. https://doi.org/10.1016/0731-7085(94)00103-0

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