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
When preparing dissolution medium with pH 6.8
phosphate buffer and sodium lauryl sulfate,we are
obtaining a very hazy solution.Do you have any
suggestion about what it might be?
A
Sodium lauryl sulfate is incompatible with potassium salts.
Therefore,when adding this surfactant to your dissolution
medium,you should prepare your buffer solution using the
corresponding sodium phosphate salt.
QFor the performance verification of USP Apparatus
1 and USP Apparatus 2,we use the USP Prednisone
Tablets and USP Salicylic Acid Tablets. What
are the tablets to be used in the performance verification
of USP Apparatus 4?
There are no procedures available to check the performance
of USP Apparatus 4 beyond the descriptions given in
USP,EP,and JP.At present,the performance verification of this
equipment is only through confirmation of temperature,flow
rate,and cell dimensions.Additional studies to evaluate
enhanced compendial performance verification are not
planned at this point.Apparatus 4 is an important product
performance tool used increasingly for novel dosage forms
such as microparticulate systems and drug-eluting stents. In
the near future,increased use and interest in Apparatus 4 may
increase the need for more detail regarding performance
verification checks.
Q
Could you describe the major factors that could
affect the dissolution testing of suspensions and
which dissolution apparatus could be used with this
type of dosage form?
A
When developing a dissolution test for a suspension,the
following items should be evaluated carefully:1) Preparation
of the sample � the sample should be prepared in the same
way as prepared by the patient.Therefore,the product should
be resuspended according to the label instructions. 2) Sample
size � In most cases,the amount of suspension to be transferred
to the dissolution vessel should be equivalent to one
dose. If with this sample size,surfactants will be needed,it is
preferable to reduce the sample size to avoid using surfactants.
3) Sample transfer � When transferring the sample to
the dissolution vessel,a rapid and uniform dispersion is desirable.
The place where the sample is going to be delivered
should allow this rapid dispersion.The sample placement will
vary from one formulation to the other,and it should be very
well described in the final version of the dissolution procedure.
The dissolution testing of suspensions can be carried
out using either USP Apparatus 2 or USP Apparatus 4.
Q
At what temperature should the pH of the dissolution
medium be adjusted,room temperature or 37 �C?
A
The pH of the buffers used in the preparation of dissolution
media should be adjusted at room temperature,then
transferred to the dissolution vessel and equilibrated at 37.0 �
0.5 �C.
Q
How is the standard solution prepared when
working with a drug substance that has poor solubility
in the dissolution medium?
A
One approach is to transfer the amount of drug substance
needed to a volumetric flask,add a certain amount of a watermiscible
solvent to aid the complete solution of the reference
standard material,and dilute to volume with dissolution
medium.Another possible approach is to prepare a stock
solution in an appropriate solvent,then transfer an aliquot to
a volumetric flask and dilute to volume with dissolution
medium. In both cases,the influence of the addition of the
water-miscible solvent on the quantitation procedure should
be evaluated.
Q
Is there any guidance or standard procedure
regarding running a blank (dissolution medium in
the seventh vessel) with each dissolution test?
A
As far as we,know there are no guidances or standard
procedures on this topic.Using the seventh vessel as a control
on the medium,vessel,and cleaning procedures has merit.
Good analytical chemistry principles should be applied in
deciding to use this approach or not.