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
What grade of water is used to prepare dissolution media?
A
It is recommended to use Purified water (USP monograph) in the preparation of dissolution media. See the Reagents, Indicators, and Solutions section of USP 28, page 2791.
Q
Is peanut oil used in the preparation of dissolution
media?
A
The effect of food on the release mechanism of pharmaceutical
dosage forms can be evaluated in vitro using
dissolution media that can simulate the in vivo conditions.
This type of media can be prepared with a pH range from
1.2 to 7.8 to mimic the gastrointestinal tract. Enzymes and
bile salts can be added to this media to mimic foodinduced
changes in the different parts of the GI tract. Also,
the addition of oil to the media can simulate the fatty
component of a meal. Several vegetable oils, including
peanut oil, can be used for this purpose. See El–arini, S. K.,
Shiu, G. K., Skelly, J. P. – Theophylline–controlled release
preparations and fatty food:An in vitro study using the
rotating dialysis cell method. Pharm.Res., 7(11):1134 –
1140, 1990.
Q
Which are the possible compositions of dissolution
media?
A
The list of possible dissolution media is very long.You
can find several different dissolution media in the USP
monographs, in the new general chapter <1092> The
Dissolution Procedure:Development and Validation,
published in Pharmacopeial Forum 31(5): 1463 – 1475,
2005. Also, you can find suggestions of dissolution media
in papers published in Dissol.Technol. and at
www.NCBI.NLM.NIH.GOV (access free of charge).
Q
When evaluating the dissolution of pharmaceutical
dosage forms containing poorly soluble drugs,
if the addition of surfactants or a hydroalcoholic
medium is not appropriate, can buffers of high pH,
i.e.above pH 8.0, be used?
A
The selection of the media composition for dissolution
testing is based on the need for discriminatory power and
ruggedness of the test, on the stability of the analyte in the
test medium, and on the relevance to in vivo performance.
Oral formulations should be evaluated in the physiologic
pH range of 1.2 to 6.8 (1.2 to 7.5 for modified–release
formulations). The use of a dissolution medium with pH
outside of these ranges should be justified. The use of
organic solvents is discouraged. Surfactants may be used
to enhance drug solubility. The type of surfactant and the
concentration employed should be justified by dissolution
profiles in the different conditions. Sodium lauryl sulfate is
not always the best option, the surfactant should be
compatible with the drug substance and with the composition
of the medium, and this is not always the case for this
particular surfactant. Possible surfactants used in dissolution
testing are:
) You can find useful information on the selection of the type and concentration of surfactants in dissolution medium in these two papers: 1 – Noory, C., Tran, N., Ouderkirk, L., and Shah, V. – Steps for development of a dissolution test for sparingly water–soluble drug products. Dissol.Technol. 7(1): 16 – 18, 2000. 2 – Brown, C. K., Chokshi, H. P., Nickerson, B., Reed, R. A., Rohrs, B. R., Shah, P. A. – Acceptable analytical practices for dissolution testing of poorly soluble compounds. Pharm.Tech., Dec 2004, 56 – 65.
Q
Q During the stability studies of an extendedrelease
tablet what basis should be used in the
calculation of amount of drug released; the assay
result obtained at the time point of the evaluation
or the label content?
A
All results in the evaluation of dissolution testing are
calculated based on the label claim of the product or on
the dose released (this is case of transdermal patches and
osmotic pump tablets) and not on the actual assay result.
Q
For the evaluation of drug release of a product in
a suspension for injection (depot), the USP apparatus
4 seems to be the instrument of choice.Which
are the cells that could be used with this apparatus?
A
The drug release of suspensions for injection (depot),
liposomes, nanospheres, microspheres, etc., can be evaluated
using USP Apparatus 4 with the 12 mm or 22.6 mm
tablet cell depending on the sample size. Often the
suspension is placed in the middle of the glass bead bed
that may fill the cell. The manufacturers of this apparatus
can customize the cells according to the characteristics of
your product. Figure 1 shows some of the cells that can be
used with USP Apparatus 4.