Questions and Answers November 2016
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: firstname.lastname@example.org
Q We are developing a new tablet formulation and would like to know which performance test we should develop, disintegration or dissolution.
A The recommendation is always to start by developing a dissolution test. Then, based on the physical-chemical characteristics of the drug substance (mainly solubility) and on the behavior of the dosage form during the dissolution test (information taken from the dissolution profiles), it may be possible to use a disintegration test in place of the dissolution test. Either performance test needs to be sensitive to changes in the critical quality attributes of the dosage form. Chewable tablets and orally disintegrating tablets are the only dosage forms that might need both disintegration and dissolution tests. Typically, all other dosage forms will have only one test, dissolution or disintegration.
Q In our laboratory we have USP Apparatus 2 with 2-L vessels. Can we use it even if we are employing only 1 L of dissolution medium?
A The dissolution general chapter allows the use of 1-L as well as 2-L vessels. These vessels share a common diameter and differ with respect to height. You can use a 2-L vessel with a smaller medium volume such as 900 mL. If the 2-L vessel is used this way, you need to be sure that you are sampling at the right sampling point as described in the USP General Chapter <711> Dissolution.
Q Have there been any changes to the USP General Chapter <711> Dissolution regarding the use of 10-mesh baskets?
A Every time USP makes a revision in any monograph or general chapter, this revision is published in Pharmacopeial Forum (PF) for a period of 90 days for public comments. Nothing is changed, updated, added, or deleted without being published in PF. PF is available free of charge at www.usppf.com. The text of USP General Chapter <711> Dissolution contains information only about the 40-mesh basket. This size is considered the default. Any other size can be used with appropriate justification. See USP General Chapter <1092> The Dissolution Procedure: Development and Validation, item 1.4 Choosing an Apparatus. If the monograph text does not specify the mesh size of the basket, it means that it is 40 mesh. Any other mesh size will be specified in the monograph text. You can see all the details for dissolution, disintegration, and drug release tests mentioned in USP at http://www.usp.org/usp-nf/overview/compendial-tools/usp-dissolution-methodsdatabase. USP General Chapter <2040>Disintegration and Dissolution of Dietary Supplements cross-references to <711> for the description of equipment.
Q What is meant by other “validated” sinkers can be used for dissolution as stated in USP General Chapter <711>? Could I use a purchased sinker that matches the same dimensions as the sinker I made as per <711> or do I have to do a validation study on it first in order to use it?
A You can use any type of sinker, even those commercially available. Sinkers can be found in several designs and sizes. You need to evaluate different sizes and designs to select the type that is the most suitable for a particular product. Ideally, the results of dissolution testing for the product will be less variable with the sinker than without. Validation will take into account the relevant elements given within Section 5, Validation in General Chapter <1092> The Dissolution Procedure: Development and Validation. Do not forget to take into consideration possible dosage form swelling due to hydration on contact with the dissolution medium. Because the design of the sinker may have an effect on the dissolution performance of a dosage unit, a detailed description of the sinker is part of the procedure.