Dissolved oxygen as a measure for de- and reaeration of aqueous media for dissolution testing

Abstract

It order to obtain reliable and reproducible remits from dissolution tests, it is often necessary to deaerate the dissolution medium. In the current work, four different methods of degassing the medium were compared by measuring the concentration of oxygen in the medium before and after the deaeration procedure. The oxygen concentration was determined under defined conditions by using an oxygen sensor bused on a Clark electrode. The method described in the USP 23 (heating to 45°C plus filtration) achieved an H5% ±11% reduction in the oxygen concentration. Heating to 100"C resulted in a reduction of only 50% ±3%, while filtration reduced the oxygen content by 65% ±4%. A method developed in our laboratory combining ultrasound and application of a vacuum achieved a 95% ±2% reduction. After degassing, the medium must usually be transferred to the dissolution vessels before the test is run. The results indicated that even careful filling resulted in a 37% increase in the oxygen content, while typical filling procedures resulted in an almost three-fold increase. It was further shown that the medium gradually becomes re-saturated during the dissolution test itself, ill a rate that is dependent on the apparatus (basket versus paddle) and the rotational speed. 120 minutes into the test, the oxygen concentration was already 60% of the saturation value. Conclusions: The measurement of oxygen was demonstrated to be a reproducible and direct method for measuring the efficiency of deaeration. it was further shown that the efficiency of deaeration is highly dependent on the method used, and that re-introduction of air into the medium occurs not only ditringfilling of the dissolution vessels but also during the dissolution test.