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 I would like to obtain information on developing a dissolution test for oral suspensions.
A The apparatus of choice is USP Apparatus 2,paddle,but there are some companies that have developed dissolution tests for oral suspensions using USP apparatus 4,flow cell. For the paddle,the rotation,in most cases,is between 25 and 50 rpm.You can use other rotation speeds but they must be justified.The medium composition is chosen in the same way as it would be for a tablet or capsule.The most important step in the dissolution test for a suspension is the introduction of the sample into the vessel.The sample should be delivered into the medium so that its dispersion is rapid and uniform. Generally,the amount of sample introduced should be equivalent to one dose. To avoid the use of surfactants,smaller sample amounts can be used.The placement of the sample will depend on the density and viscosity of the suspension. In testing with the paddle,the sample can be introduced anywhere into the vessel:at the top of the dissolution medium,midway between the top of the liquid and the bottom of the vessel,underneath the paddle,or in any other position.The sample introduction needs to be specified and needs to be evaluated during the validation of the procedure. Apparatus 4,flow-through cell,has been used for testing oral suspensions either with variations in the bead level for the two official cells or with an alternative cell.

Q I would like to know the criteria for selecting paddle or basket apparatus for dissolution testing of capsules and tablets.
A The use of the paddle or basket when developing a dissolution test is primarily determined by practical rather than theoretical considerations.The paddle is the favored apparatus for most oral dosage forms. It is not as useful for those dosage forms that are buoyant. For buoyant capsules and tablets,the basket should be the first choice. In specific cases, where for example the basket mesh may become obstructed by gelatin or other matter,use of the paddle would be favored.When testing buoyant dosage forms with the paddle, a sinker is usually required.

Q How can I verify the suitability of dissolution apparatus using 4-L vessels?
A The USP General Chapter,<711> Dissolution describes the Apparatus Suitability Test for Apparatus 1 and 2 which utilizes USP Dissolution Calibrator Tablets according to the operating conditions specified.These operating conditions are most appropriate for 1000-mL capacity vessels.Typically,it is recommended that for applications where either the 2000- or 4000-mL vessels are used,the suitability testing should be done in the apparatus but with the 1000-mL vessels. For the suitability determination of an assembly for dissolution testing using 4000-mL vessels,the recommendation is that all mechanical variables be determined to conform to those specified in the General Chapter and that the calibrator tablets be run in the apparatus using the conditions given. Since the assembly for a 4000-mL vessel is significantly different in dimensions from that for a 1000- or 2000-mL vessel,an insert that allows the positioning of a 1000-mL vessel should be used for the suitability testing.

Q The apparatus suitability test for the reciprocating cylinder has changed.Where was this announced and when was the change made official?
A USP Apparatus 3,reciprocating cylinder,no longer includes testing with the theophylline beads as part of the apparatus suitability test. Typically,changes affecting the availability of reference standards or in this case the use in a General Chapter are made official by the most immediate vehicle available.The change was first announced as In Process Revision,page 715 of Pharmacopeial Forum,volume 29 number 3,May-June 2003. The official date of the revision was October 1,2003 and can be found in the Fifth Interim Revision Announcement,page 1397 of Pharmacopeial Forum,volume 29 number 5,September-October 2003. At the time of the official announcement,USP 27 was being published without the revision. This was necessitated both by the USP publication schedule and to allow for the possibility that late public comment could have been received necessitating postponement or modification of the revision. The revision is included in the First Supplement to USP 27,official April 1,2004.