Questions and Answers August 2026

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 In the USP general chapter <1724> Semisolid Drug Products - Performance Tests, the vertical diffusion cell (VDC) rack is typically connected to a thermostatically controlled water bath recirculatory. Can the water bath be considered a regulated heating system, meaning that an alternative heating system cannot be used (e.g., a heating block)?
A There are no restrictions on the heating system for the cells. A water bath or any other approach can be used as long as the temperature is maintained and controlled at the appropriate temperature. Keep in mind that the temperature is 32 ?± 1 ?°C for products applied to the skin and 37 ?± 1 ?°C for products intended for internal application.

Q For Models B and C described in the USP general chapter <1724> Semisolid Drug Products - Performance Tests, what is the volume of the vertical diffusion cell (VDC)? The FDA Guidance for Industry - Nonsterile Semisolid Dosage Forms-Scale-Up and Postapproval Changes: Chemistry, Manufacturing, and Controls; In Vitro Release Testing and In Vivo Bioequivalence Documentation" (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/supac-ss-nonsterile-semisolid-dosage-forms-scale-and-post-approval-changes-chemistry-manufacturing), describes a diffusion cell system with a standard open cap ground glass surface with 15-mm diameter orifice and total diameter of 25 mm. Does this correspond to any specific USP apparatus (A, B, or C)?
A The FDA guidance indicates "One possible in vitro release study design is summarized below.," meaning that other designs are allowed. The actual volume of each cell needs to be determined to calculate the mass balance and flux rates in the system. From <1724> (text reprinted with permission of USP):

Q Could simulated intestinal fluid be used with a product where cross-linking due to the gelatin cross-linking is evident, or in what cases could it be used? Compared to the USP general chapter <711> Dissolution, there is a substantial difference in the amount of pancreatin added to the medium.
A Information regarding the enzymes and amounts to be used when there is evidence of cross-linking in gelatin capsules can be found in <711> Dissolution. The enzyme to be used should be selected based on the pH of the dissolution medium. In <711> Dissolution, the activity of the enzyme is specified in units/L of media. In contrast, the composition of simulated intestinal fluid as described in USP Test Solutions and Indicator Solutions (Intestinal Fluid, Simulated, TS) does not take into account the proteolytic activity of pancreatin. More information about cross-linking in gelatin capsules can be found in the USP general chapter <1094> Capsules - Dissolution Testing and Related Quality Attributes and in the paper by M. Marques entitled "Enzymes in the Dissolution Testing of Gelatin Capsule" (AAPS PharmSciTech, 2014, DOI: 10.1208/s12249-014-0162-3).

Q Regarding delayed-release dosage forms, in the USP general chapter <711> Dissolution, Method A, where it starts with 750 mL of acid medium and, in the buffer stage, 250 mL of buffer medium is added to the vessel containing the acid medium. If the sampling time in the buffer stage is 45 minutes, will this time start after adding buffer medium to the last vessel?
A No. The test time for the buffer stage of the dissolution experiment begins after the addition of the buffer medium to each individual vessel containing the 750 mL of the acid medium. Depending on whether the sampling is manual or automated, the addition of the buffer medium may be done in such a way to allow each vessel to be sampled at the appropriate time after the buffer medium is added to the vessel.

Q We have a dissolution instrument with seven vessels. We use the seventh vessel for the blank. Is it necessary to evaluate this seventh vessel when doing the performance verification test of the dissolution equipment?
A The seventh vessel and position need to be qualified only if used to test samples. In this case, make sure that you compare the acceptance criteria for the six-vessel dissolution system. There may be slight differences in the %CV upper limit based on the number of vessels used in the dissolution run.

Q How do you apply Acceptance Table 2 for extended release dosage forms as described in <711> Dissolution for the time points where the acceptance criteria is not a range? As an example, the tablet label claim is 500 mg and at the first time point the acceptance criteria is not more than (NMT) 40% and the last time point is not less than (NLT) 80%.
A The amount released for an extended-release dosage form is typically calculated based on the product label claim. In practice, the acceptance criteria is always a range. Consider the example provided. The range for the first time point is actually 0-40% of the product label claim, and the range for the last time point is 80-100% of the product label claim. Even when the acceptance criteria are stated as NLT or NMT a single value, in practice, the acceptance criteria represent a range of acceptable values.

Q When performing the performance verification test using USP Dissolution Performance Verification Standard (DPVS) - Prednisone tablets, do the tablets need to be weighed prior to performance of the dissolution experiment?
A No. The tablets do not need to be weighed before the dissolution experiment. DPVS - Prednisone tablets are packaged in blister cards with push-through foil lidding. As with other pharmaceutical dosage forms, the label claim of the content, 10 mg of prednisone, should be used to calculate the percent release values, which are then used to determine the geometric mean and %CV.