Methods of Degassing

There are various methods of degassing media — helium sparging, warming, and subsequent filtering and vacuum degassing are the most popular. The method suggested in the USP is to heat the media to 45°C then filter it through a 0.45µm filter under vacuum and stirred for about 5 minutes before being placed directly into the dissolution vessel (the paddles/baskets should be switched off until the analysis is ready to start). At no time must the temperature be allowed to drop below 37°C. This method of degassing has been shown to reduce the level of dissolved gases by about 85% which is enough to ensure that the air will not affect the dissolution results.

Helium sparging can be effective but is costly to use for large volumes, as it requires a constant supply of helium gas to continually bubble through the media. It degasses the liquid by absorbing the gases that are dissolved in the media into the helium bubbles and carrying them out of solution. One of the major problems with this method is that the media can become saturated with helium which causes similar problems to being saturated with air and it is difficult to measure the amount of helium in the liquid.

Heating and filtering the media is fairly reliable and is the method described in USP 23 (it actually specifies heating to 45 °C, followed by filtration through a 0.45µm filter membrane). This will remove about 85% of the dissolved oxygen, although the media then has to be cooled before the dissolution test which gives it time to reaerate.

Vacuum degassing can remove more than 95% of the dissolved gas and if the media is held under vacuum (as it is in the Dosaprep) then it will not be able to reaerate before it is placed in the dissolution vessel.

Other common laboratory methods of degassing such as sonication or membrane degassing are not practical for degassing the large volumes required for dissolution testing and are more suited for HPLC.

A summary of the percentage reduction in dissolved oxygen using various techniques is shown below (data from Dissolution Technologies, August 1998).

Method % Reduction (approximate)
USP 84.9 ± 11%
Filtering only at room temperature 65 ± 3%
Heating to 45°C 10 ± 14%
Boiling 49 ± 3%
Vacuum degassing 50-90%