The following questions have been submitted by readers of Dissolution Technologies. Tahseen Mirza, Ph.D.*, United States Pharmacopeia, authored the reponses to each of the questions.

 

Q My question deals with the interpretation of the Acceptance Table 1 in the General Chapter <724> of USP 24. At the L2 stage, should the statement ". none is more than 10% of labeled content outside each of the stated ranges" read as "none is more than 10 units of labeled content outside each of the stated ranges." For instance, if the specified range is 42% ­ 52%, is the acceptance range 37.8%-57.2% or 32%- 62%?

A The correct range in this example is 32%-62%. I believe that the key words in this statement are 10% of labeled content.' This is also clearly stated in the paragraph immediately above the Acceptance Table 1 where it states that "limits on the amounts of the active ingredient dissolved are expressed in terms of the percentage of the labeled content." Therefore, a range of 37.8%-57.2% can not be the correct answer. If the statement had referred to '10% of the stated range' instead of '10% of labeled content,' only then would the calculated range be 37.8%-57.2%.

Q In order for Dissolution Apparatus to pass System Suitability test, is it necessary for the Apparatus to pass the acceptance criteria for both calibrator tablets viz. Prednisone and Salicylic Acid tablets? Can we use only this Prednisone calibrator tablets?

A For a Dissolution Apparatus to comply with USP specifications for System Suitability testing, it must pass acceptance criteria for both Prednisone and Salicylic Acid calibrator tablets.The Salicylic Acid tablets represent the non-disintegrating type and Prednisone tablets represent the disintegrating type of dosage forms. The Prednisone tablets are very sensitive to the amount of dissolved gases in the dissolution medium and somewhat sensitive to centering. Therefore, Prednisone is a good calibrator to determine degassing efficiency. Preliminary data has shown that Prednisone tablets can also discriminate between the design differences of the Apparatus. Salicylic acid is sensitive to several other variables and it is the appropriate calibrator for baskets. Since it does not disintegrate and stays within the basket, it is designed to pick up the variables that are unique to baskets i.e. Apparatus 1.

Q Do you have a procedure for calibration of a dissolution unit with 3-L capacity vessels?

A It is important for me to point out that the 3-L dissolution vessels are not officially recognized by the USP. In the Dissolution General Chapter <711>, only 1-, 2- and 4-L vessels are recognized and their detailed dimensions are given. Therefore, I cannot support the use of 3-L dissolution vessels. If possible, try to use the 2- or 4-L vessels. Another point that needs clarification is that the calibrator tablets are designed to test the entire system that comprises of the analyst, apparatus and the analytical instrument /procedure. The vessels are a component of the apparatus and hence a part of the system. When the system passes the test, it is an assurance that all the components including the vessels are in working condition. The Dissolution Apparatus is calibrated using only 1-L flasks. It is not necessary to repeat the calibration with the larger volume vessels. If you must use 3-L vessels and cannot use the other USP recognized vessels; you can apply a similar approach and calibrate the Apparatus with 1-L flasks. However, you have to bear in mind that it is your responsibility to justify the use of the non-USP compliant vessels.

Q Is there a USP Dissolution test for beta-Carotene? If not, is USP planning on coming up with a Dissolution standard in future?

AThe current USP 24/NF 19 does not have Dissolution standards for oil-soluble vitamins. Only Disintegration as described in USP General Chapter <2040> is necessary to demonstrate the release of the vitamins from the dosage form. In the future, USP may consider Dissolution requirements for oil-soluble vitamins. A new USP subcommittee (Bioavailability and Nutrient Absorption) was recently formed and will be responsible for dealing with this issue. Please check the Pharmacopeial Forum regularly to find out what actions, if any, the subcommittee will be taking on this issue.

*Note: These are opinions and interpretations of the author, Tahseen Mirza, Ph.D., and are not necessarily the official viewpoints of the USP.

Answers provided by: Tahseen Mirza, Ph.D., M.B.A.
Pharmaceutics Section Leader
USP Research and Development Laboratory and
Liaison to the USP Subcommittee on
Dissolution and Bioavailability