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
The procedure for qualifying USP Apparatus 3
requires two sampling times. It seems that the
procedure is intended to ensure that the apparatus
is suitable for testing extended-release products.
I use it for testing an immediate-release product
that only needs to be sampled at one time. How
should the qualification of USP Apparatus 3
(reciprocating cylinder) be done if the equipment is
not going to be used to evaluate modified dosage
forms?
A
The USP General Chapter <711> Dissolution states that
the performance verification of the USP Apparatus 3
should be done by using the USP Chlorpheniramine
Maleate Extended-Release Tablets RS. The detailed
procedure on how to carry this verification can be found
at
http://www.usp.org/pdf/EN/referenceStandards/chlorpheniramineMaleate.pdf.
This procedure should be
followed regardless of the type of samples that are going
to be tested in the apparatus.
Q
Can sinkers be used with tablets, or is their use
exclusively for capsules?
A
Please refer to the USP General Chapter <711>
Dissolution, under Apparatus, Apparatus 2 (Paddle
Apparatus). Sinkers can be used with any dosage form
that floats in the dissolution medium. This general chapter
states that a small non-reactive wire helix may be attached
to the dosage form to keep it at the bottom of the vessel.
An alternative sinker device is described in Figure 2a in
this general chapter. This sinker is the one mentioned in
the Japanese Pharmacopoeia, and it was incorporated
in the USP general chapter when this chapter was
harmonized with the Japanese Pharmacopoeia and
European Pharmacopoeia. Other validated sinker devices
may be used. The USP General Chapter <1092> The
Dissolution Procedure: Development and Validation gives
more details on how to prepare the wire helix sinker.
Sinkers have been used to avoid sticking of film-coated
tablets to the vessel walls.
Q
What is the difference between degassing and
deaeration?
A
According to John Burmicz in the Technical Note: Why
Is Vibration an Issue for Dissolution Testing?, published in
Dissolution Technol. 2008, 15 (1), 29�31, "degassing is a
technique whereby dissolved gasses with a high solubility
product can be displaced by a gas with a lower solubility
product. Typically, helium can be used to displace both
nitrogen and oxygen in aqueous media. Deaeration, on
the other hand, is a method by which we physically
remove the dissolved gasses from the medium."
Q
What should be the minimum hardness of the
water to be used in the preparation of dissolution
medium?
A
The water used to prepare the dissolution medium
should meet the requirements of the USP monograph for
Purified Water.
Q
We perform a dissolution profile from 12 tablets.
Samples are taken at 5, 10, 20, 30, and 45 min with
medium replacement. The monograph requires the
test to be evaluated at the 30-min sampling. Is it
correct to report the results for the first six tablets
from the 30-min sampling? We would make sure
that the results for the second set of six tablet were
similar to the first.
A
With twelve units tested, you should not disregard any
data collected. Therefore, the first six could be compared
to the S1 criteria in Acceptance Table 1 (General Chapter
<711> Dissolution), but you will need to compare the
entire set of data to the S2 criteria as well. You should
designate in advance the set of tablets that you will
consider against the S1 criteria and document that choice.
Because the monograph test only includes one test
time point, the procedure that you describe is strictly
interpreted as an alternative. A discussion of alternative
methods is given in the USP General Notices under Tests
and Assays.
Q
In USP <711> Dissolution, Acceptance Table 1
gives no upper limit for dissolution results. When
we are testing the dissolution for an immediate-
release product, what should be the maximum
value found? According to USP content uniformity,
the maximum value should be greater than 100%
but less than 115% of label claim. Is this not so?
A
General Chapter <711> Dissolution has no upper limit
specified for dissolution results summarized in Acceptance
Table 1. The emphasis for the performance testing of
immediate-release products is on products that do not
release an adequate amount. Confirmation of the amount
of drug per dosage unit is given by the assay and by
<905> Uniformity of Dosage Units. Please note that for
<905>, the criteria have changed, and now the calculation
of Acceptance Value (AV) is required. Changes to the
Uniformity of Dosage Units general chapter are explained
by an entry on the USP website under Compendial
Notices. The explanatory note can be accessed at
http://www.usp.org/USPNF/notices/generalChapter905.html.