Comparison of the Effectiveness of Various Deaeration Techniques (2004)

Introduction The USP General Chapter 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”(1). Dissolved gases present in dissolution media can affect the results in a number of ways. The dissolved gas can significantly change the pH of an unbuffered solution, can interfere with the fluid-flow patterns through bubble formation, and can change the nature of the active ingredient and alter analytical values (2). Deaeration of dissolution media is therefore required to ensure that dissolved gases do not affect the results of a dissolution experiment. Deaeration will not prevent air from being trapped in pockets in the dissolution apparatus. Air pockets have been discussed elsewhere (2) and are beyond the scope of this work. The USP recommends deaeration by a combination of heating and vacuum filtration followed by vigorous stirring of the medium under vacuum (1). To date, many authors have reported data for various deaeration techniques using vacuum filtration, heating, sonication, membrane filtration, and inert gas purging (3-7). Of these techniques, the least cumbersome and time-consuming method was the inert gas purge method (6), however, cost may be a consideration(3). Rolli and co-workers (8) have reported that the inert gas purge method was expensive due to lack of a good hardware design. Once deaerated, the dissolution media must be transferred to a dissolution vessel and then stirred over the course of the dissolution run. One concern is the potential for the media to become reaerated during this time. Diebold and co-workers (7) showed that reaeration of dissolution media during media transfer is a concern as dissolved oxygen increased 275% in their study. Therefore, the determination of the effectiveness of deaeration techniques must also include a discussion of the potential for reaeration and the degree to which various factors impact the rate of reaeration. The Dissolution chapter also states that other validated deaeration methods are acceptable. However, it is difficult to determine what is considered a validated method because to date, there is little data to show the effectiveness of the deaeration techniques. To this point, neither a desired level of dissolved gas nor acceptable validation standards for the methods are stated. This study was undertaken to evaluate various current deaeration practices and summarize the difference in effectiveness of each technique. Abstract Many methods have been described for the deaeration of dissolution media, as required by the USP as well as worldwide regulatory agencies. The USP General Chapter Dissolution suggests heated vacuum filtration as one method of deaeration. This method of deaeration, when performed in our laboratories with 1L of water produced media with 2.8 mg/L dissolved oxygen remaining. Helium sparging achieved lower levels of dissolved oxygen. Helium sparging produced media deaerated to the same level as the USP vacuum filtration technique if the media was sparged at a flow rate of 40 mL/s for approximately 0.5 minutes per liter of media container volume. This recommendation is based on the fact that partially filled containers of dissolution media did not deaerate as efficiently as full ones. Other parameters such as media volume, gas flow rates, degassing time, analyst variability, and inlet filter pore size were all investigated to determine their effect on the deaeration process. The helium sparging deaeration technique was also effective for deoxygenating other aqueous dissolution buffers. Deaeration by heated vacuum filtration, DissofillTM (automated heated filtration system), or by inert gas sparging prevented visible bubble formation during the dissolution experiment. However, monitoring of dissolved oxygen levels over the course of an entire dissolution experiment showed that more efficient deaeration of the dissolution media had no discernible effect on the final level of dissolved oxygen.