Pharmacy Courses

Dissolution Method Development and Media Selection for a New Dosage Form

When you are working on a new dosage form and need to develop a dissolution method, the first places you should look are the USP and FDA Dissolution Method Databases.  If your product is found in these databases, then that can be a lot of potential help - BUT you should not consider your method development work to be done.

You'll notice as you look through these databases that many drugs have multiple methods listed.  The reason for this is that the 1st, 2nd, 3rd, etc. methods were not found to be appropriate for a formulation and a new one needed to be developed.  

You will need to do work to find if the method(s) listed are actually acceptable for your product. Formulations are always changing, so these methods may not reflect your dosage forms - especially since many methods in these database will be several years old.

The other challenge is that these methods are not complete dissolution methods.  So, even if the method is correct for your formulation, you will still need to determine all of the other aspects of your method that aren't listed.  Some examples would be:  appropriate filter type and use, sinkers, surfactants, acceptable tolerances (allowable pH variability), etc.

These databases can be excellent shortcuts - but shouldn't constitute a completed method.  You will still need to fully develop and validate the method for yourself with the formulation you're working with.

To choose the right dissolution media the first step in this is to do a quick solubility study.  Create 4-5 stock medias between pH 1.1 - pH 7.5.  For each pH, use 4-5 volumetric flasks.  In those volumetric flasks, test different surfactants as well as no surfactant.  Add your API at your dose strength to each flask, and mix with an orbital shaker, rocker, etc.  Review all of your flasks and determine visually what has an hasn't dissolved.  Review the matrix you've created.

If your API has been able to dissolve in 250 mL, then it means that you would be at sink condition at typical dissolution volumes.  

Remember that sink condition means you can dissolve 3x the amount of drug that is in the dosage form.  3 x 250mL is only 750mL - and most methods are 900mL.

If you do see that you need some surfactant to dissolve, you can then focus on those conditions and create additional flasks of the media with lower levels of surfactant to determine what is needed.

This simple solubility won't pick your dissolution media for you, but it will certainly eliminate a lot of options before you even get to a dissolution unit.

Resource Person: Ken Boda (Dissolution Product Specialist at Agilent Technologies)

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