dx.doi.org/10.14227/DT330126P38

Questions and Answers February 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 <1092> The Dissolution Procedure — Development and Validation, under 5.1 Specificity/Placebo interference, it is stated that any interference should not exceed 2.0%. Is this requirement applicable for degradants or any other component, and if it is applicable to placebo/blank interference?
A The requirement that the interference should not exceed 2.0% is applicable to interference from any of the components specific to the dissolution method and formulation, including:

Q Is it acceptable to have an assay value of 95% and then the dissolution test gives 105%. The Q value is 70%, knowing that the acceptable range for the assay is 90-110%?
A Yes, it is possible to have dissolution results above 100%, but the source of the high dissolution value should be investigated. As only one dosage unit is introduced in each dissolution vessel/cell, this unit may have a drug content close to the upper limit of the uniformity of dose. An investigation would typically be required to rule out other sources for the high value. Possible sources of interference that may result in dissolution results above 100% are listed above. Other reasons for high values may include method-related issues such as inappropriate filter selection or sampling procedure.

Q If a validated method with manual sampling is being used, and the procedure is optimized using an autosampler, keeping the same test conditions except for the sampling volume (with medium replacement) because the equipment requires a larger volume, is it necessary to perform a new validation? Or is the qualification of the equipment enough?
A In addition to proper qualification of the sampling system, additional validation steps must be completed to demonstrate that there is no sample adsorption in the system and that the sampling system is not contributing other components (e.g., leachables and extractables) that may interfere with the quantitative step. This evaluation needs to be done for each product where the automated/semi-automated system is implemented.

Q We would like clarification regarding the degassing procedure described in USP <711> Dissolution. The chapter specifies that the medium should be filtered under vacuum while mixing vigorously, then continue mixing under vacuum for approximately 5 minutes. The General Notices state that "vacuum" denotes exposure to a pressure of less than 20 mmHg (2.67 kPa), unless otherwise indicated. On the other hand, USP <1092> The Dissolution Procedure “ Development and Validation, states that “The extent of deaeration can be evaluated by measuring the total dissolved gas pressure or by measuring the concentration of dissolved oxygen in water. For example, an oxygen concentration below 6 mg/L has been found effective as a marker for adequate deaeration of water for Dissolution <711>, Apparatus, Apparatus Suitability, Performance verification test with USP Prednisone Tablets RS.” However, the certificate for the Dissolution Performance Verification Standard “ Prednisone states the recommended degassing procedure as follows: “Measured vacuum should be less than 100 mbar.”
A Please note, the general chapters use the term “deaeration” while the USP reference standard certificate uses the term “degassing.” In the context of removing dissolved gases from dissolution media, these two terms are used interchangeably. Please also note that the definition of “vacuum” provided in the General Notices states, “unless otherwise indicated.” The information in <1092> regarding the performance verification test with USP Prednisone Tablets RS is provided as an example of a specific deaeration technique for a specific product. In this example, a specific dissolved oxygen limit of 6 mg/L was found to be effective to ensure consistent dissolution results. The recommended degassing technique in the certificate for the Dissolution Performance Verification Standard — Prednisone (i.e., measured vacuum should be less than 100 mbar) provides sufficient reduction in dissolved oxygen and other dissolved gas(es) that may be present in dissolution media; however, consider that this method was developed and validated for a specific product as well. For general dissolution purposes, the degassing methods and dissolved gas limits may vary based on the specific formulation and media degassing equipment used. The degassing method and dissolved gas limits should be considered as part of the dissolution method validation procedure when it can be shown that dissolved gas has an impact on the dissolution results for a specific product.

Q USP general chapter <711> Dissolution states that sinkers can be used if the dosage form floats in the dissolution medium. Is the use of sinkers allowed with USP apparatus 2 (paddle) even if the compendial monograph for a particular drug product does not mention its use?
A Sinkers can be used if the dosage form floats or if it sticks to the equipment walls. In many cases the use of sinkers is product-dependent. If sinkers are needed, they can be used even if the compendial monograph does not mention its use. If it is determined that a sinker is needed for a specific product, the appropriate design and size should be selected on a caseby-case basis and should be described in the final dissolution method because the use of an inappropriate sinker may compromise the dissolution results.

Q I am working on a project for a dosage form containing a polymeric nanomaterial. I found information in the literature that N-methyl-2- pyrrolidone can be used as co-solvent in dissolution media. What co-solvent concentration is allowable for dissolution method development?
A One of the main objectives of the dissolution test is to be discriminative for the critical quality attributes. Consequently, if the use of co-solvents is deemed appropriate, then the type and concentration should be selected to maintain the discriminatory power of the dissolution test. The type, concentration, and purity of any co-solvent used in a dissolution method needs to be determined using a case-bycase approach, utilizing data obtained from the sample under evaluation, and should be scientifically justified.

Q In the USP general chapter <711> Dissolution, under Procedure, Apparatus 1 and 2, Time, it states, “Specimens are to be withdrawn only at the stated times, within a tolerance of ± 2%.” For immediate-release products, this toleranceshould be fine, but is the tolerance of ± 2% applicable for extended-release products, wherein the time points will be 8, 12, or even 18 hours?
A This tolerance level is applicable to the time to initiate the sampling procedure. It does not account for the entire duration of the sampling procedure. The sampling should start at the time specified in the method within the tolerance of ± 2% of the specified sampling time. This tolerance is applicable to all types of dosage forms, to all types of sampling procedures (manual, automated, or semi-automated), and to all types of dissolution testing including dissolution profiles.

Q Can the dissolution test replace the disintegration test for immediate-release solid dosage forms? If yes, are there published regulations that discuss this issue and clarify the conditions in which this case can be applied.
A USP general chapter <1711> Oral Dosage Forms “ Performance Tests provides instruction for cases where a disintegration test is appropriate based on different types of solid oral dosage forms. Generally, you should always start with the development of a dissolution test whenever possible. Then, depending on the physical-chemical properties of the drug substance and on the dissolution profile, the dissolution test may be replaced with a disintegration test with appropriate justification based on the data obtained from the samples being evaluated.