The USP monograph has eight testsįor dissolution, each with different dissolution conditions. Q We are planning to produce a nifedipine extended- release tablet. In summary, accurate dissolution results will represent the total mass dissolved, whether present in the medium or taken for analysis, and use the actual volume of medium at the time of sampling. As you can see in this example, the error from the amount of drug removed somewhat cancels the error in assuming no loss of volume. Table 1 illustrates the cumulative effect of neglecting the volume removed (no replacement) and dissolved drug removed over three sampling times with 20 mL removed at each time point. If the sampling volume taken is not replaced, then the actual remaining volume must be used in calculations of total amount dissolved. In the calculation of dissolved drug, the medium volume is a scalingįactor from concentration to total amount in solution. The effect of the removal of medium volume is an additional consideration. The decision of significance is a matter of interpretation, but the decision should be documented and should become part of the standard procedure. If a significant amount of dissolved drug is removed, it should then be included in the calculation of total amount dissolved at each subsequent time. Is there a calculation to correct the results when we replace the sample volume? What is the correction if we do not replace the sample volume?Ī dissolution test with multiple sampling times will produce erroneous, inaccurate results if the amount of sample (medium volume or dissolved drug substance) removed at early sampling times is not considered in calculations of results for subsequent sampling times. *Note: These are opinions and interpretations of the authors,Īnd are not necessarily the official viewpoints of the USPĮmail for USP says that for multiple sampling times, the sample aliquot should be replaced with an equal volume of fresh medium, but if the replacement is not necessary, the calculations should correct for the volume change. and Will Brown, United States Phamacopeia, authored
Have been submitted by readers of Dissolution Technologies. Question and Answer Section - February 2011
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