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 How can I evaluate the effect of deaeration of the dissolution media on dissolution results?
A One possible approach to evaluate the effect of the deaeration in the dissolution results could be running the dissolution profile of the product under evaluation both with untreated medium and with deaerated medium and verifying the impact of these conditions on the profile. Also,it may be useful to do this evaluation with samples with known deviations (deviations from the formulation and/or manufacturing process) and under stressed stability conditions.

Q What are the differences in the dissolution conditions for chewable tablets?
A Basically, the dissolution test used for chewable tablets should be the same as that for conventional tablets. Due to the non-disintegrating characteristics of the dosage form, occasionally it may be necessary to alter some test conditions such as increasing the agitation rate and/or the test duration. For more information see:Shah,V. P.,Siewert, M., Dressman,J.,Moeller, H., Brown,C. K. � Dissolution/in vitro release testing of special dosage forms, Dissolution Technologies, 9(1): 6�11, 2002;Siewert, M.,Dressman,J., Brown, C.,Shah,V. � FIP/AAPS Guidelines for dissolution/in vitro release testing of novel/special dosage forms. Dissolution Technologies 10(1): 6�15, 2003.

Q Which dissolution media are appropriate for buffered or effervescent tablets?
A The criteria for the selection of dissolution media for buffered or effervescent tablets are the same as for conventional tablets.You should consider the physico-chemical characteristics of the active ingredient (solubility,pKa or pKb,etc). Probably because of the characteristics of this kind of product you will need to use a buffered medium. It will be advisable to verify if the buffering capacity and ionic strength of the media are appropriate for the formulation under evaluation.

Q Please give some information on the f₁ and f₂ calculations for dissolution profiles.
A Dissolution profiles can characterize a dosage form more precisely than a single point dissolution test. Comparison of dissolution profiles between pre- and post-approval changes,or products with different strengths,or products from different manufacturers,can help in assuring similarity in product performance and may alert for possible bioinequivalence.Moore and Flanner [Pharm.Tech. 20(6):64 � 74,1996] proposed a mathematical approach to compare the dissolution profile using two factors, f1, difference factor, and f2,similarity factor.The factor f2 measures the closeness between the two profiles. See Shah,V. P.,Tsong,Y.,Sathe,P., Williams, R. L. � Dissolution profile comparison using similarity factor, f2. Dissolution Technologies, 6(3):15,1999 for the mathematical formulas to calculate these two factors.

Q How are the dissolution conditions selected when the dosage form contains more than one active ingredient?
A The same approach used for dosage forms containing only one active pharmaceutical ingredient (API) still applies (sink condition, agitation rate, tolerances,etc). In some cases, all the dissolution conditions are the same for all the APIs but with different tolerances for each drug substance. Depending on the differences of the solubilities of the active ingredients, it may be necessary to have separate sets of dissolution conditions, one for each API.

Q How do I know if I have a discriminating dissolution method?
A You will have a discriminative dissolution method when the dissolution profile obtained with this method can show different results when the manufacture or composition of product changes. These changes can be in the formulation,process,equipment,materials,etc. The goal is to develop product specifications that will ensure bioequivalence of future batches. A new dissolution method should be challenged to be sensitive to variations that can have an impact on the in vivo performance of your dosage form. For instance, for one product the crystal form of the active pharmaceutical ingredient (API) may be critical and for another product the critical parameter may be particle size of the API, or a step in the manufacturing process. The FDA Guidance for Industry � Dissolution Testing of Immediate Release Solid Oral Dosage Forms (www.fda.gov/cder/ guidance/1713bp1.pdf) gives more details and some references on this topic.

Q What are the storage conditions and shelf life for the fasted state simulated intestinal fluid and fed state simulated intestinal fluid published in Dissolution Technologies 11(2)?
A The blank solution can be stored under usual buffer storage conditions with no special requirements. The fasted state simulated intestinal fluid can be kept one week in the refrigerator, and the fed state simulated intestinal fluid should be freshly prepared.

Q How can the level of vibration be measured around dissolution equipment? What is acceptable?
A The vibration in the close vicinity of the dissolution equipment can be monitored using a vibration meter, available in catalogs and from vendors of dissolution equipment. The USP Dissolution General Chapter <711> states �No part of the assembly, including the environment in which the assembly is placed, contributes significant motion,agitation or vibration beyond that due to the smoothly rotating stirring element�. There are no numerical limits for vibration. It is up to you to monitor the vibration around your dissolution equipment and to verify if this vibration level is interfering with the test.You can use the USP calibrator tablets to check if the vibration level is acceptable or not.

Q Which is the most appropriate procedure to clean dissolution vessels?
A One possible procedure is to wash the dissolution vessels by hand using a soft cloth and water with a very small amount of detergent,rinsing with tap water,followed by rinsing with purified water and ethanol. Depending on the nature of the residue on the vessel walls,it may be necessary to pre-treat the vessel with methanol or an acid or an alkali prior to the use of a detergent (sometimes detergent is not used at all), with the use of ultrasound or not.Care must be taken not to scratch the internal surface of the vessel,therefore the use of abrasive materials or tools should be avoided. It is important to not allow build up of residue from detergents.