FAQs: <1092> The Dissolution Procedure: Development and Validation

1. How can I find the right filter for my dissolution procedure?

The right filter will not adsorb the analyte when the dissolution sample solution is filtered. A number of filter materials are available increasing the probability that a good match can be found. The adsorption of the analyte to the filter may be saturable, meaning that it can only adsorb a certain amount of the analyte. If that is the case, a specific discard volume of sample solution filtrate can be found that allows subsequent filtrate concentration to be representative of the concentration of analyte dissolved in the sample. Typically milliliter increments of filtrate are passed through the filter cartridge and collected separately. The response of the analyte is measured in each increment and compared with the unfiltered solution. The amount of discard is determined from the results.

2. Does <1092> apply to parenteral drug forms?

The main focus of <1092> is solid oral dosage forms. Much of the information can also be applied to other dosage forms.

3. In the UV determination of our dissolution samples the absorbance of the capsule shell exceeds the 2% limit for placebo interference given in the chapter. How can this interference be overcome?

Using a more specific method such as HPLC as an alternative can help.

4. I have trouble dissolving my standard in the dissolution medium. Can I use an organic solvent like methanol to help prepare the standard solution?

Under Validation, <1092> mentions the use of solutions made with not more than 5% organic solvent when evaluating Accuracy/Recovery and Linearity and Range. The use of the organic solvent is to promote the dissolution of the pure material but not interfere with the analysis. The solvent should not interfere with the analysis at the concentration used.

5. The procedure for extended release products calls for sampling at three specified times with different levels of dissolution. Do we need to validate the analysis at each concentration?

Validation provides confidence that the analysis will return the correct results. This is true at any expected concentration such as is found when testing different strengths of product and also when multiple time points are specified. Validation of the analysis should be done to assure the results over the range expected for the analysis when it is applied to the product.

6. Our dissolution sample is turbid, how can we perform the filter interference study?

The sample can be centrifuged to remove turbidity. The supernatant can then be used for the filter interference study.