Questions and Answers February 2022
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.
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Q In the USP monograph for Metaxalone Tablets, Dissolution Test 1, the medium is 0.5% Sodium Lauryl Sulfate, 900 mL. There is no mention of the solvent used to prepare this medium. How should it be prepared?
A In the entire text of USP-NF, when the solvent is not mentioned, purified water should be used. See USP General Notices 6.50.20 Solutions.
Q When water with pH around 5.8-6.0 is used as dissolution medium, which enzyme is appropriate when there is evidence of cross-linking in gelatin capsules?
A The enzyme to be used in the dissolution testing of gelatin capsules that present cross-linking is selected based on the medium pH. See USP general chapter <711> Dissolution, under the section For Dosage Forms Containing or Coated with Gelatin. In the case of a dissolution medium with pH 5.8-6.0, papain or bromelain should be employed.
Q Is it possible to introduce more than one dosage form unit in the dissolution vessel?
A No. See USP general chapter <711> Dissolution, where it is stated that only one dosage form unit should be introduced in the apparatus (i.e., vessel, reciprocating cylinder, or flow-through cell).
Q How many decimal places should be used when expressing dissolution results? If the Q value is NMT 75%, how should the results be reported?
A The results must be reported with the same number of significant figures as the acceptance criteria. See USP General Notices 7.10 Interpretation of Requirements.
Q How should a non-pharmacopeial sinker be validated? One can assume that as a minimum, method precision would be analyzed and in connection to this a result comparison to the method not using a sinker. Is anything more required? Is a comparison with a pharmacopeial sinker needed?
A Sinkers are product dependent. The appropriate model/design/size of sinkers should be evaluated for the specific dosage form. There is no need to compare with a “pharmacopeial” sinker, but the use of the sinker should be justified. The size and shape of the sinker should be appropriate for the product being evaluated, otherwise it can slow down the disintegration and dissolution of the dosage form. The sinker should be validated through visual observation and by evaluating the dissolution profile. Once the appropriate sinker has been selected, it should be well-described in the final version of the method to avoid variability in the dissolution results and facilitate method transfer.