Effects of Dissolved Gases in Surfactant Dissolution Media

Introduction Dissolved gases,with dissolved oxygen serving as the primary marker,have been widely documented to influence dissolution experiments. The dissolved gases can cause changes in the performance of the dissolution medium by changing pH,forming bubbles on the dosage form or altering the interaction of the medium and the active pharmaceutical ingredient [1]. Extensive studies have been performed examining appropriate techniques for the removal of dissolved gases from aqueous media which include a combination of heating and vacuum filtration followed by stirring under vacuum (USP method),vacuum filtration, heating alone,sonication,helium sparging,and membrane filtration [2-6]. Regardless of technique,reaeration of the media is a concern. Reaeration can be defined as the process of gases from the atmosphere dissolving into the liquid phase raising the level of dissolved gases. Studies have shown that regardless of technique used to remove dissolved gases,reaeration will occur,and the equilibrium dissolved oxygen value will be relatively unaffected [7]. The only influence the technique will have is the amount of dissolved gas removed,and the time it will take for the media to equilibrate to atmospheric conditions. Media that have reached equilibrium do not exhibit performance changes stemming from the technique used to remove the dissolved gases. While the effect of dissolved gases on aqueous media has been studied extensively,the effect on surfactant containing media has not been addressed directly. The USP General Chapter <711> states,“dissolved gases can cause bubbles to form, which may change the results of the test. In such cases,dissolved gases should be removed prior to testing”[8]. This statement does not specify type of media,but suggests that if dissolved gases do not affect the results,the level of dissolved gases can be largely ignored. This study investigates whether the level of dissolved gases is a source of variability that should be monitored when performing dissolution tests that utilize a surfactant-containing medium by examining the dissolution performance of oral dosage forms in media with a range of dissolved oxygen levels. Furthermore,the USP method of dissolved gases removal along with other accepted methods will be examined to determine their influence on equilibrium values of dissolved gases.