dx.doi.org/10.14227/DT130306P34

Question and Answer Section

William Brown and Margareth Marques
The following questions have been submitted by readers of Dissolution Technologies. Margareth Marques, Ph.D. and Will Brown, United States Phamacopeia, 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: web@usp.org

Q When running dissolution tests for products with very low strength,is it acceptable to use multiple dosage units in each vessel?
A The use of multiple dosage units in each dissolution vessel is not recommended because it is very difficult to assure that all units will be in contact with the dissolution medium in the same way.The contact interface between the dosage unit and the medium will not be the same for all units in all vessels, presenting a very high variability in the results .There are other approaches that are more appropriate:(1) the use of 200-mL vessels with mini paddles,just keep in mind that because this apparatus is not compendial,you need to justify its use,demonstrate that it brings an advantage to the test, validate it,and develop a verification procedure;(2) use of an analytical technique with more sensitivity. Some companies are using liquid chromatography coupled with mass spectrophotometry to quantify the low amounts of drug typically released from drug-eluting stents.

Q We are observing failing results when we are doing the equipment verification with USP Prednisone Tablets RS.We carried out the test with and without sinkers,and we observed the failure just with the use of sinkers.Do you have any comments?
A
Sinkers are used only when the dosage form floats.The USP Prednisone Calibrator Tablets do not float.Therefore,the use of sinkers is unnecessary.As in your case,the use of sinkers can have an influence on the dissolution test results. In fact, the particular sinker design that is used should be specified. Thus,sinkers,when needed,will be specifically included in the procedure with a description of the design that must be used. The procedures for dissolution apparatus performance verification are available at http://www.usp.org/ referenceStandards/useAndStorage/calibrators.html.

Q Regarding the dissolution test of extendedrelease dosage forms,can we claim that our product is USP if we have our own tolerance test that is different from those stated in a particular USP monograph?
A No. In order to claim that your product is USP,it needs to meet the acceptance criteria in all tests included in a particular USP monograph. For a test like dissolution,several procedures with associated acceptance criteria might be included. Each marketed product would have to indicate in its labeling the particular procedure and criteria that apply.What could be done for your product is to request the inclusion of an additional dissolution test procedure and acceptance criteria in the USP monograph.As USP represents products that have been approved by the FDA,your request for revision of the monograph dissolution test should include a copy of your dissolution test,its validation report,and a copy of the FDA approval letter.

Q Are other procedures for degassing the dissolution medium,other than the one described in USP, acceptable?
A Yes,in the USP general chapter <711> Dissolution,page 2679 of USP 29,there is a footnote describing one possible procedure for degassing dissolution medium. In this footnote is stated that �other validated deaeration techniques for removal of dissolved gases may be used.�Please refer to the following papers:Griffith,M. F.,Curley,T. E.,Marting,G. P., Considerations in choosing a deaeration technique for dissolution media. Dissolution Technol.,February 1997,pages 16�17;Degenhardt,O. S.,Waters,B.,Cameirao,A. R.,Meyer,A., Brunner,H.,Toltl,N. P.Comparison of the effectiveness of various deaeration technique. Dissolution Technol.,February 2004,pages 6�11;Fliszar,K. A.,Forsyth,R. J.,Li,Z.,Martin,G. P. Effects of dissolved gases in surfactant dissolution media. Dissolution Technol.,August 2005,pages 6�10. See pages 15�18 in this issue.

Q Could an orally-disintegrating tablet be classified as a chewable tablet? Could the same dissolution procedure be applicable for both dosage forms?
A Chewable and orally-disintegrating tablets are formulated in different ways,and they have different performances. Chewable tablets are intended to have the active participation of the patient who,by chewing the tablet,facilitates the act of swallowing it.There is no guarantee that the patient will follow the instructions completely,and swallowing the whole tablet is a possibility.Therefore,the dissolution test for this dosage form is done in the same way as for simple tablets. Orally-disintegrating tablets are a more recent technical breakthrough.Typically,these dosage forms are designed to disintegrate rapidly in the presence of liquid to facilitate their administration.As the rapid disintegration is a special characteristic of this dosage form,a disintegration test is necessary. Typically,drugs have bad taste;to overcome this in an orallydisintegrating tablet,the drug is coated. Release of the drug from the coated particles must be demonstrated.Therefore,a dissolution test is also included in the specification of this dosage form.

Q How should the acceptance criteria in the Acceptance Table 2 in the USP general chapter <711> Dissolution be interpreted,mainly regarding the statement "none is more than 10% of labeled content outside each of the stated ranges"?
A Acceptance Table 2 in <711> Dissolution is used to evaluate the results for extended-release dosage forms.The Q value and all the percentage values mentioned in the tolerances of dissolution tests and in the acceptance tables are expressed in the same terms as percentages of the labeled amount of the drug. In the statement,outside means both above and below the range endpoints. For instance,suppose that for the timepoint 1 hour you have a range of between 20% and 30% of the drug released.Applying the statement in the acceptance table,you will end with the new range of between 10% (20% minus 10%) and 40% (30% plus 10%).