Questions and Answers November 2024

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 have Peak vessels in our lab and we would like to know if the performance verification procedure (PVT) is applicable to these vessels.
A Peak is a brand name from a specific manufacturer. The generic name of this type of vessel is apex vessel. There is no PVT procedure for apex vessels. The Dissolution Performance Verification Standard - Prednisone tablets was developed specifically for use with Apparatus 1 and Apparatus 2 as described in general chapter <711> Dissolution. The suitability of dissolution equipment should be verified using standard vessels.

Be aware that, as apex vessels are not standardized, their dimensions may vary from one supplier to another. When replacing a broken apex vessel, the replacement should come from the same supplier.

Typically apex vessels are the last option, and their use requires justification obtained with the sample under evaluation. Before using apex vessels simply increasing the rotation speed is a good place to start to see if problems with a dissolution method can be resolved.

Q We are doing a dissolution test with a tablet that has a very low label claim. The dissolution procedure states to use 900 mL of dissolution medium and quantification by spectrophotometric procedure. We are obtaining low absorbance values. Can we change the volume to 500 mL?
A If the dissolution method was developed using 900 mL, you cannot change any of the dissolution conditions without a justification. An alternative way of solving this problem is to use UV-Vis cells with a longer pathlength, like 5 cm or 10 cm. This approach would allow you to obtain higher absorbance values without making any changes to the dissolution procedure.

Q I am doing some research work in tablet disintegration. As it is widely known, tablets and capsules need to disintegrate within 15 and 30 min respectively to pass the USP disintegration test. I would like to know how the 15- and 30-min timing came about.
A The 15- and 30-minute criteria mentioned above is simply a suggestion. Actually, there is no established acceptance criteria for disintegration. The acceptance criterion for disintegration is formulation-dependent and must be justified with data obtained from the samples being evaluated.

Q What are the limits for enzymatic activity of pepsin to be used in dissolution?
A The limits for enzyme activity mentioned in general chapter <711> Dissolution describes the upper limit for enzyme activity in the dissolution medium. Because the activity of enzymes can vary from lot to lot, the activity of any enzyme to be used in dissolution testing must be determined prior to preparing the dissolution medium. Use the procedure referenced for each enzyme in the USP general chapter <711> Dissolution. Using the activity value determined experimentally, the weight of enzyme is calculated to obtain the appropriate activity per unit volume as stated in <711>.

Q USP General Chapter <711> states: “Time: Where a single time specification is given, the test may be concluded in a shorter period if the requirement for the minimum amount dissolved is met. Specimens are to be withdrawn only at the stated times, within a tolerance of ±2%.” Is this point applicable for manual withdrawal or for automated sampling? What is the minimum time (single time) considered for the tolerance limit of ±2%., For example, if a single time specification is given at 15 minutes, then it is quite difficult to withdrawal within the specified tolerance limit.
A The tolerance for the sampling time of ±2% is applicable to both manual and automated sampling. If the sample is going to be taken at 15 minutes, the range to start the sampling is 15 ± 2%. Keep in mind that the dissolution process stops only when the dissolving particles are removed from the dissolution media. Consequently, sampling includes both removing the sample from the dissolution vessel and filtering the sample. As a result, early sampling time points can be challenging for both manual and automated sampling methods.