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Thoughts on Small Volume Dissolution

Posted by Pam Bialiy on

The following article has been authored by John Heaney.

Compared to the rest of dissolution testing, small volume dissolution is in a bit of a strange position within the industry.  The bulk of dissolution testing is set around well-defined apparatus with specific dimensional tolerances and a 1 L glass vessel with a hemispherical bottom.   Small volume dissolution can vary widely, the main commonality being that the maximum capacity of the vessels is significantly smaller than 1 L.

The first question one may ask is why do small volume dissolution at all?  As pharmaceutical technology improves, with better chemistry and things like nanotechnology able to improve bioavailability; some API’s simply do not require the larger doses they did in the past to be effective.  This means less drug in the tablet, which can mean fewer side effects for the patient.  However, it also means less drug in the dissolution test which may mean the analysts run into issues with detecting and quantifying the amount of API present in the dosage.  Small volume dissolution testing helps with this problem by being able to perform the dissolution test in less media than would be required in larger dissolution vessels.  Typically 50 mL to 250 mL depending on the vessel and method requirements.  It’s important to note that small volume dissolution still requires sink conditions for the API, it just has less dissolution media for the test.

Small volume dissolution is only compendial in the Chinese Pharmacopeia at the moment.  In the US, things are not standardized and the type of small volume vessels and apparatus available may vary by manufacturer.  This means that moving ahead with a small volume dissolution method requires that proof be available to justify why standard apparatus cannot be used.  Additionally some care should be used in the equipment selection as small volume dissolution apparatus  should not be confused with the immersion cell apparatus which use flat bottomed vessels.

Another potential issue is that the methods may not be easily transferable as any facility would need to have the same apparatus available which may vary by manufacturer.  Dissolution testers from 2 different manufacturers may not have the same small volume dissolution apparatus available.  Dimensions between manufacturers can vary drastically, so if a method transfer is going to occur where the apparatus may be different, it’s important to perform the necessary studies to make sure the data is comparable, or ideally similar.

While small volume dissolution does have some unique challenges, it can provide a path to dissolution testing of low dosage products that Apparatus 1 and Apparatus 2 are unable to do.   It can reduce additional operations, such as concentrating samples, needed prior to analysis which provides more consistent data.  It’s also adaptable to most existing dissolution testers, which means there’s no need to purchase a whole new dissolution tester.

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