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When validating the analysis portion of the dissolution method, one test that should be performed is spiked placebo or recovery. This is done to ensure that the API can be properly analyzed in the presence of all of the excipients in a formulation without any significant interference. This test is usually done at an n=3 with 2 analysts, and you are looking to have fairly tight agreement between the 3 samples (<3% RSD is what I have seen in the past). Specificity testing can be done with this same sample and you would be looking for interference <1%.
The samples for this test are prepared by making a placebo mixture of everything that is in the final dosage form. If you're working with multiple strengths of the same drug, you could determine the worst case scenario (highest amount) of each of the components for the mixture. When making the placebo mixture, the order the excipients are added may be very important. Some placebos when mixed together may form insoluble clumps for example - which doesn't help for proper assessment in the test. Talk with your formulations team if possible for help in determining a good order of addition and procedure for mixing the components.
Once you have this mixture created, you can spike the placebo mixtures with known levels of drug as a standard. This would usually be done by pipetting different volumes of a stock solution into each flask. I would recommend standard concentration levels corresponding to the beginning of the dissolution run, at or near full release, and another level overdose to make some wiggle room for potential future changes. 10-50%, 80-100%, and 120-130% are some concentrations to consider.
I've been asked several times if these mixtures should be made in dissolution vessels, and the answer is no. Volumetric flasks offer better volume accuracy, and can easily be put on a shaker or sonicator. They also can be cleaned in a dishwasher which is helpful since some of these excipient mixtures can be sticky.
Sample from the volumetric flasks using the filter you've validated for your dissolution analysis. That filter validation is one of the first steps of any dissolution method development - so if it hasn't been done yet, start there first.
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