Questions and Answers May 2023

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 adapting a sampling system to our dissolution equipment that can be connected to a sampling robot. With this new system the probe remains inside the vessel during the entire test. We have more than 80 products that will be tested using this new system. What evaluations or qualifications do we need to perform in this situation?
A The suitability of this new system must be demonstrated for each one of the products. Drug adsorption, leachables, extractables, and the possible interference of having the sampling probe resident inside the vessel must be evaluated for each one of the products that are going to be analyzed with this system. It is possible that this system will not be suitable for some of the products. All these evaluations must be documented.

Q We are running a dissolution test of hypromellose capsules with 0.01 N HCl, pH 2.0, at 37 °C, and the dissolution is not complete in 15 minutes. We would like to know if we can add enzymes as stated in USP general chapter <711> Dissolution.
A No, the addition of enzymes as stated in <711> Dissolution is not likely to solve the issue. The enzymes described in <711> are proteases and are intended to be added to the dissolution medium when there is evidence of cross-linking in gelatin capsules. Since hypromellose is not a protein, it is a cellulose derivative, capsules made of this material may naturally take longer to dissolve. You may need to evaluate different dissolution times and agitation speeds in the dissolution test validation procedure.

Q For the preparation of simulated gastric fluid, can we use a different pepsin activity?
A Yes, you can use pepsin with any activity, you just need to weigh an amount to provide an activity of about the middle range of 800-2500 units per 1000 mL of dissolution media.

Q Should the linearity range for the validation of a dissolution method include the lowest point in the dissolution profile?
A The linearity range for the validation of dissolution method should include all points in the dissolution profile. The validated range should include the lowest expected level up to and including the upper limit of uniformity of dosage units.

Q Why was a new Prednisone tablet reference standard released?
A The release of the new USP Dissolution Performance Verification Standard - Prednisone RS is a part of USP's commitment to continuous enhancement of our products and services. The introduction of this new reference standard and the associated revisions to General Chapter <711> Dissolution are being recommended based on feedback from various USP stakeholders.

Q What is the difference between the new reference standard USP Dissolution Performance Verification Standard - Prednisone RS (catalog #1222818) and the current reference standard USP Prednisone Tablets RS (catalog #1559505)?
A Based on internal USP studies that have been performed, the new reference standard is considered more sensitive to operational and mechanical variables of instrument setup, less sensitive to media degassing, and more reproducible. The packaging configuration has also been changed. Each blister pack of six tablets is packaged in an aluminum sachet to provide additional protection against moisture.

Q Will the USP Prednisone Tablets RS be discontinued?
A Yes, the current reference standard USP Prednisone Tablets RS will be discontinued on or about April 28, 2023 in anticipation of the associated revisions to General Chapter <711> Dissolution becoming official on May 1, 2023.

Q Can I still use the current reference standard (USP Prednisone Tablets RS catalog #1559505) for PVT after the official date of the revised documentary standard?
A No, USP Prednisone Tablets RS (catalog #1559505) cannot be used to meet the requirements of apparatus suitability in General Chapter <711> Dissolution where the use of USP Dissolution Performance Verification Standard - Prednisone RS is specified.

Q Will USP provide a guidance documents and resources like the Dissolution Toolkit to help with mechanical calibration and PVT using the new reference standard?
A Yes, the updated guidance document “USP Guideline on Procedures for Mechanical Calibration and Performance Verification Test Apparatus 1 and Apparatus 2” is currently available on the PVT landing page https://www.usp.org/smallmolecules/ pvt and under the Compendial Tools section on the USP website at https://www.usp.org/resources/compendialtools

Q If the new USP Dissolution Performance Verification Standard - Prednisone RS tablet has decreased sensitivity to degassing, then is degassing the media still required?
A Yes. The collaborative studies were conducted requiring the USP method for degassing media, so degassing media is still required to successfully complete the performance verification test.