Questions and Answers August 2025

Margareth R. Marques, Ph.D. and Mark Liddell, Ph.D.
The following questions have been submitted by readers of Dissolution Technologies. Margareth R. Marques, Ph.D., and Mark Liddell, Ph.D., United States Pharmacopeia (USP), authored responses to each of the questions. *Note: These are opinions and interpretations of the authors and are not necessarily the official viewpoints of the USP.
Email for correspondence: mrm@usp.org

Q We are developing a new dissolution method, and we would like to know if we can use PEAK vessel to avoid cone formation?
A PEAK vessel (Agilent) is a trademark name. The generic name for this type of vessel is apex vessel. Apex vessels are not compendial equipment and their use must be justified. If you are using the basket, increasing the rotation speed may be required. If this change does not solve the coning phenomena, you may need to move to the paddle apparatus and select the appropriate rotation speed as part of the method validation. Typically, after exhausting the above compendial methods, then the use of apex vessels may be justified. As these vessels are not standardized, using vessels from the same supplier will help to ensure consistency in test results.

Q We are developing an oral suspension product that will be filled in multi-dose containers as well as unit dose cups. For dissolution testing, we are planning to pool the content of ten unit-dose cups into a larger container, to perform the testing. Six sample aliquots will be added to the six separate dissolution vessels for testing. Is this procedure appropriate?
A For any type of suspension, the dissolution test should be done with the samples reconstituted according to the instructions to the patient. The amount of sample to be transferred to the dissolution vessel must be equivalent to the highest dose that can be administered as a single dose. According to the description above this method would only satisfy the compendial requirements for suspension testing if the amount of drug in the aliquot transferred to the dissolution vessel is equal to the amount contained in highest administered dose and if the suspension is reconstituted according to the patient instructions.

Q I have trouble dissolving my standard in the dissolution medium and I've looked online for the information from https://www.usp.org/frequently-asked-questions/dissolution-procedure-development-and-validation. The answer is: “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 solubility of the pure drug substance but not interfere with the analysis. The solvent should not interfere with the analysis at the concentration used.” If 5% organic solvent is not enough to solubilize the drug substance in my standard solution, is it acceptable to add more organic solvent (up to 10%) and perform method validation to prove that the solvent does not interfere with the analysis at the concentration used?
A This would be acceptable under the condition that the composition of the standard solution and sample solution are similar. The only acceptable difference should be the amount of the analyte in the two solutions. If higher amounts of organic solvent are used to dissolve the standard, it needs to be demonstrated that this difference between the composition of the standard solution and sample solution does not interfere with the quantitation of the drug substance in both solutions. We would also recommend checking the solubility of the drug substance in the literature and evaluating whether other organic solvents can be used.

Q Can 100% organic solvent be used to dissolve poorly soluble drugs for dissolution standard solution preparation?
A The composition of the standard solution and sample solution should be almost identical, the difference should be the amount of the analyte in the solutions. One common method to prepare standard solutions is to first prepare a stock solution using an organic solvent. Then, an aliquot of the stock solution can be transferred to a volumetric flask and filled to volume with dissolution medium. The amount of organic solvent in the aliquot should be no more than 5% of the total volume of thefinal dilution with dissolution medium. Another option is to transfer an appropriate amount of standard to a volumetric flask, add a volume of the appropriate organic solvent not more than 5% of the total final volume, and then complete the dilution to the final volume with dissolution medium.

Q We have a dissolution method in our lab that uses 10 mesh basket. The performance verification test (PVT) of USP apparatus 1 was designed for 40 mesh baskets. Can we use this procedure with 10 mesh baskets?
A No. Because a collaborative study was used to establish the acceptance criteria for the PVT test reference standard (USP DPVS - Prednisone Tablet RS) and the use of 40 mesh baskets was specified in the collaborative study protocol, the acceptant criteria for USP apparatus 1 can only be applied to a dissolution apparatus that uses 40 mesh baskets. As an alternative, you can qualify the dissolution system using the standard 40 mesh baskets and then perform a mechanical calibration of the system after installing the 10 mesh baskets to ensure that the 10 mesh basket height, wobble, and centering are all within acceptable tolerances. Also, each time the dissolution equipment is used, the 10 mesh baskets should be inspected to ensure that the baskets are still in good condition.

Q Dissolution test 2 in the USP monograph for Pseudoephedrine Hydrochloride Extended-Release Tablets calls for the use of a nylon netting. What are the specifications for this material?
A Keep in mind that the dissolution test 2 in the USP monograph for Pseudoephedrine Hydrochloride Extended-Release Tablets is specific for an osmotic pump tablet and may be formulation dependent. The nylon netting mentioned in the text is used to hold the tablet in place and it does not play any other role in the dissolution test. This nylon netting is also known as tulle fabric, and it is used for bridal veils or for mosquito nets.

Q The USP procedure for the determination of the enzymatic activity of the pepsin to be used in the dissolution test states to use 2.5 mg of pepsin to prepare the sample solution. Is this amount applicable to any kind of pepsin or should this amount be modified considering the protein content of the pepsin being evaluated?
A It is important to note that only purified pepsin is recommended for use as an enzyme in dissolution media with a pH ≤ 4.0. The amount of 2.5 mg is appropriate for a sample of purified pepsin. The procedure determines the proteolytic activity of the purified pepsin to be used in dissolution media and not the amount of protein contained in the sample.

Q For how long can the temperature of the dissolution medium be out of the range 37.0 ± 0.5 °C during a dissolution run?
A The temperature of the dissolution medium must be within the range 37.0 ± 0.5 °C during the entire dissolution test. There are no allowances for excursions. If the dissolution bath cannot maintain the temperature of the dissolution media throughout the dissolution test, preventative maintenance or repair of the dissolution equipment may be required. See USP general chapter <711> Dissolution.

Q Regarding the use of enzymes in the dissolution media for dosage forms containing gelatin, if the dissolution medium is water, which theoretically has a pH of 7, but can actually range between pH 5 and 8. Should we use the theoretical pH of 7 and use pancreatin for a dissolution test using water as the media or should we measure the pH for each dissolution and adjust the enzyme accordingly depending on the pH of water?
A Determine the pH of the water that is going to be used as the dissolution medium and select the appropriate enzyme for the measured pH. Keep in mind that the pH of water may change upon storage.