Dissolved Gasses in Dissolution Testing

Deaeration of dissolution media is one of the more confusing parameters for many dissolution chemists.  Depending on the lab, you may see degassing for all products, no products, or a mix - and when you do degas, there are a variety of ways in which labs can degas.

First, dissolved gasses are a critical parameter that needs to be explored as part of dissolution method development for every dosage form.  Dissolved gasses may or may not have an impact on the dissolution of a product - but you need to validate your approach unless you are following the USP <711> vacuum degassing procedure.

Dissolved gasses can have many impacts on the dissolution test, and overall, dissolved gasses tend to lead to higher and more variable results.  The changed behavior of dosage forms can be due to: causing particles to float, acting as an abrasive force on the tablet/capsule, causing spinning or dancing of dosage forms, aggomerating product together, etc.  At times, air bubbles can lead to lower values as well, such as with blocking basket mesh or covering a transdermal membrane.

To determine if degassing is required, you should perform n=12 with degassed media per USP and compare it to non-degassed media.  Once you have the data from these two n=12s, you can perform an f2 analysis or other statistical approach to determine if there is a significant impact.  If there is not, you can consider the method validated without need of degassing.  If you do find there is a significant difference, you either can use the USP degassing method OR you can validate an alternate degassing method instead, in the same fashion that you checked with non-degassed media.

The most common alternate approaches to degassing other than the USP method are helium sparging and automated degassing devices.  Both of these approaches can work well, but do need to be validated against degassed media.  Validation can be done through the f2 as above, or through a measurement of dissolved oxygen (or better yet, total dissolved gasses).  If you are helium sparging, the method should dictate the flow rate and length of time that helium is to be dispensed into the media.  Approaches NOT to be used are nitrogen sparging and sonication under vacuum, the first supersaturating air in the media and the second being ineffective for aqueous only solutions.

Regardless of the degassing approach used, if you do degas, you need to begin your dissolution run as soon as possible once the media has reached temperature.  Media will usually re-aerate completely within 2 hours, most of that in the initial half hour.  Degassing in the morning, going to lunch, and then starting a run isn't going to offer a very degassed media.

Not all dosage forms are impacted by dissolved gasses.  Generally, media with surfactant re-aerates very rapidly and degassing has little impact (and is difficult anyway).  Extended release products tend to be less susceptible than immediate release dosage forms.  Disintegrating dosage forms tend to have more issues than do non-disintegrating dosage forms.  Some dissolution apparatus will have variable challenges with dissolved gasses, and the Apparatus 3 doesn't require any degassing at all given its robust mixing.

If and how you degas needs to be defined on a product to product basis, and should not be a one approach fits all approach in the lab.  Determining which methods are and are not sensitive to them can be very worth the validation time and cost - lowering the number of runs requiring degassing, and ensuring that when a product is sensitive to dissolved gasses that there is an appropriate procedure to take care of those samples.