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
Which is the type and purity of the lecithin
recommended to be used in the preparation of
dissolution media simulating fasted and fed states
as published in Dissol.Technol. 11(2)?
A
It is recommended to use egg lecithin with a purity of not less than 98%.
Q
Is water a suitable dissolution medium?
A
There are pros and cons on the use of water as dissolution
medium.Water lacks buffering capacity. In some
cases,the pH of the medium may change as the drug and
excipients dissolve altering sink conditions. Also,water is
not considered a biorelevant medium because it does not
mimic the gastrointestinal environment. However,in some
cases water may be a more discriminative medium than
systems that otherwise are more similar to gastrointestinal
conditions. See the papers:Rethinking the use of
water as a dissolution medium, published in Dissol.Tech.
6(4), pages 6–7; and Some observations on �rethinking the
use of water as a dissolution medium�published in Dissol.
Tech. 7(2),pages 16–17.
Q
Some dissolution methods that use the USP
Apparatus 5 (Paddle over disk) sometimes mention
the use of a screen mesh.What type is this screen
mesh?
A
When testing transdermal delivery systems (TDS),the
side having the protective barrier is attached to the disk
surface using an adhesive.When the disk with the TDS is
placed in the vessel, the release surface of the system is on
the top closest to the paddle. The disk is farthest from the
paddle and merely serves to position the TDS. Thus the
screen mesh of the holder is not critical to the test.
An alternative holder,developed by the FDA, holds the patch on a watch glass under a mesh. When using that alternative device,window screen has been acceptable. Of course any material used should be evaluated for its inertness during the test.
The sample solution is withdrawn from the vessel from a point midway between the top of the paddle blade and the surface of the medium, as with USP apparatus 2, paddle,when oral products are tested. Filtration is the last step in the sample preparation.
Q
Can you recommend a procedure to qualify
and/or calibrate the USP Apparatus 7 (reciprocating
cylinder)?
A
The qualification of USP Apparatus 7 is only mechanical.
Right now there are no calibrator tablets available to check
the performance of this equipment. The mechanical parameters
that need to be verified are oscillation distance,
frequency of the oscillation, temperature of the bath,
absence of vibration, and timing of the indexer.
Q
Does the quantitative step in a dissolution test
need to be stability-indicating?
A
Most of the regulatory agencies require only the Assay
test to be stability indicating. The stability of the drug in
the dissolution test system should be evaluated as part of
the method validation. The results of the investigation of
solution stability may indicate that protection from light or
analysis within a time limit must be employed. The most
common analytical techniques used for quality control
dissolution testing will place more emphasis on speed
than the ability to discriminate degradation (e.g., UV rather
than HPLC). In some cases,depending on the nature of the
dissolution medium, the stability of the drug will not be
very good.
Q
Are there any specific dissolution methods for
ocular inserts?
A
The only USP monograph for ocular systems that
requires a dissolution test is the one for Pilocarpine Ocular
System (see page 1560 fo USP 28). The dissolution test in
this monograph does not use any of the compendial dissolution
equipment. Instead, the systems are inserted in
tubes and those are placed in a reciprocating shaker.We
are not aware of any standard methods for this type of
dosage forms.We recommend a search in the literature.
The Web site www.NCBI.NLM.NIH.GOV may be useful.