Questions and Answers November 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: email@example.com
Q USP general chapter <711> Dissolution states “The water bath or heating device permits holding the temperature inside the vessel at 37 ± 0.5 °C during the test and keeps the bath fluid in constant, smooth motion.” Is there any control that should be performed during the test to verify the temperature? We are doing a pre-test in the vessel to control the temperature and a quality control test every 3 months to ensure that the water bath is calibrated to 37 ± 0.5 °C.
A The recommendation is to check the temperature before starting the test in each vessel. Once the medium in each vessel is at the right temperature, the sensor/ thermometer should be removed from the vessel. The thermometer/sensor cannot remain in the vessel during the test. Some labs check the temperature of each vessel after finishing the test. Also, the temperature is part of the periodic equipment verification.
Q In the Dissolution Guideline Document for the new Dissolution Performance Verification Standard (DPVS) (available at https://www.usp.org/resources/compendial-tools) there is a recommendation to allowing staggered start, if possible. Should staggered start also be applied to routine sample testing?
A Yes, if the sampling is done manually, the recommendation is to stagger the introduction of sample to allow sufficient time to collect the sample and filter it before moving to the next vessel so that sampling is performed within the time tolerance of ± 2%, as stated in USP general chapter <711> Dissolution.
Q How should the disintegration results be expressed, the average of 6 units or the highest disintegration time?
A The results are expressed for each individual unit tested.
Q In the USP monograph for Isosorbide Mononitrate Extended-Release Tablets, Dissolution Test 1, it states that “tablets are placed in a metal helix prepared by winding 10 in. of a 0.8-mm stainless steel wire around a 9/32-in shaft and pulling the coils to form a helix 1-in. long.” Does the USP store sell this metal helix, or should it be prepared by winding a stainless-steel wire?
A USP does not sell any accessories used in dissolution testing. The instructions on how to make the metal helix sinker can be found in USP general chapter <1092> The Dissolution Procedure - Development and Validation.
Q USP general chapter <701> Disintegration states “The use of disks is permitted only where specified or allowed in the monograph.” Can you elaborate or provide additional criteria regarding use of disks and the applicable formulation types?
A The use of disks in the disintegration testing is defined experimentally using the samples under evaluation. Their use is defined in a case-by-case approach.
Q We are qualifying our dissolution apparatus that has eight positions. After reading USP general chapters <1058> Analytical Instrument Qualification and <711> Dissolution, we considered that dissolution equipment is in group C in <1058>, requiring installation qualification, operation qualification, and performance verification. We think that the design qualification is not necessary for dissolution equipment because they are well described in <711>. Do you have any comments on this reasoning?
A The USP general chapter <1058> provides recommendations on instrument qualification. It is up to your lab to decide how to classify the equipment. Even though design qualification may not be applicable, you need to know how the samples are inserted in the equipment and if it is possible to stagger both the sample introduction and movement of the shafts, which is important for manual sampling. Also, you need to consider if the sampling is going to be manual, semi-automated, or automated. Other aspects may be considered depending on the use of the equipment. In addition, you need to select the place where you are going to install the equipment. It must be level and free of vibration.
Q In USP general chapter <711> Dissolution and in the certificate provided with the USP Dissolution Performance Verification Standard - Prednisone RS, we found the description of the performance verification test used for the dissolution apparatus. Is the test used for performance qualification of the dissolution apparatus? Should the same procedure be used for periodical verification of the equipment? Could a finished product be used instead?
A The qualification procedure described in <711> Dissolution and in the USP RS certificate should be used for qualification of dissolution apparatus 1 and 2, both the initial test at equipment installation and for all subsequent tests.
Q For dissolution equipment with eight positions, which acceptance criteria should be used for performance verification, the criteria for six or eight positions?
A It is up to your lab to decide as it depends on how the equipment is going to be used. Consider if you will use all eight positions for samples or will six positions for samples and two positions for pre-warmed dissolution medium or placebo.