General Question : if for any product, USFDA Database suggests to perform two methods for dissolution, as test 1: USP type IV, Test 2: USP Type II, What is basic behind the concept, Does Results of both req to be submitted for the approval of the product ?
I would have thought only one dissolution method was required to be submitted. Happy to take a look at the OGD comment you are concerned with to comment further if you can point me to the particular web page you are getting this requirement from. Regards, Colin.
The FDA is suggesting to you that you need to know enough about the release mechanism of your active to guarantee that your chosen dissolution test is selective at discriminating variations in the manufacturing process that lead to dosage forms with different release profiles in vitro. Said test should be (at least) as sensitive at discriminating differences as would an in vivo release profile (what the FDA is really interested in making sure you control; but it's prohibitively expensive to test this in routine manufacturing!); usually this is easy to achieve if the release is controlled by disintegration of the dosage form to any substantial degree. In vivo the turbulent mixing in the stomach aids the release of active, whereas in vitro the dosage form may form a wetted layer which releases drug slowly through the matrix, and the stirring of the (paddles) may not be sufficient to cause this layer to fall off. If different tablets, to take an example, have even slight differences in the wetting and disintegration speed of that layer, the in vitro profiles may differ considerably, whereas the in vivo absorption profiles of the two may be quite similar. That's what the FDA is interested in; you could present either another dissolution test with different turbulence, or other equivalent types of observations --e.g., a dissolution vs. disintegration study across manufacturing ranges, with reasoned analysis of the results, or a coupled dissolution + proton NMR 3-D scan on tablets (to visualize water intrusion during dissolution). The rigor with which you pursue this point would depend on the type of dosage form you have -- unusual forms might require more testing.
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