2019

APPARATUS USED IN INDUSTRY FOR

DISSOLUTION TEST OF TABLETS

1. What is Tablet Dissolution?2

2. Tablet Dissolution Testing...................................................................................................2

3. Apparatus 1 - The Rotating Basket.....................................................................................3
4. Dissolution Baskets....................................................................................................................5
Serialisation.....................................................................................................................................6
Handling..............................................................................................................................................7
 Cleaning..............................................................................................................................................7
Storage................................................................................................................................................7
5. Apparatus 1 - Things to Think About..................................................................................7
Common problems associated with the rotating basket test.................................7
Clogging..........................................................................................................................................8
Air Bubbles....................................................................................................................................8
Low Media Agitation.................................................................................................................9
6. Running the Test...........................................................................................................................9
Inspect and Prepare Dissolution Tester.......................................................................10
Prepare Media............................................................................................................................10
Deliver Media.............................................................................................................................10
Check the Temperature.......................................................................................................10
Prepare for Sampling.............................................................................................................11
Introduce Dosage Forms to Baskets..............................................................................11
Lower Baskets into Media...................................................................................................11
Run the Test...............................................................................................................................11
Take Samples............................................................................................................................11
Measure Samples.....................................................................................................................12
Comments....................................................................................................................................12
7. Apparatus 2 (The Paddle )Test............................................................................................12
Serialisation...................................................................................................................................13
Allowable Variations..................................................................................................................13
Poly fluorocarbon Coating...................................................................................................13
8. Running the Paddle Test.........................................................................................................14
Sample Introduction...................................................................................................................14

1. What is Tablet Dissolution?

The administration of drugs via oral dosage forms is one of the
most common and effective means of delivering treatments to
patients. When a dosage form is swallowed, the rate at which it
releases the active ingredient is critical to ensure that the drug
is delivered properly. The rate at which the drug is released is
called the dissolution rate.

In fact, all drug forms have a dissolution rate. Creams, skin

patches and implants and others, all release their drugs so they
can be taken up by the body.

One of the problems facing pharmaceutical manufacturers is to

how optimise the amount of drug available to the body, i.e.
its bioavailability. Inadequacies in bioavailability can mean that
the treatment is ineffective and at worst potentially dangerous
(toxic overdose). All kinds of factors affect this from the
formulation of the dosage form, size, shape, excipients, bindings
and other physical characteristics, to the pH, temperature and so
on.

The actual drug release in the human body can be measured in-
vivo by measuring the plasma or urine concentrations in the
patient. However, there are certain obvious impracticalities
involved in employing such techniques on a routine basis. These
difficulties have led to the introduction of official in-vitro tests
which are now rigorously and comprehensively defined in the
respective Pharmacopoeia and recent harmonisation between
the various Pharmacopoeia (notably the USP, BP, EP and JP) has
lead to global standardisation in the measurement of drug
release rates.

2. Tablet Dissolution Testing

When it comes to measuring the release rates of drugs in a

manufacturing environment then the technique of Tablet
Dissolution testing is employed.

Tablet Dissolution is a standardised method for measuring the

rate of drug release from a dosage form and the key word here is
“standardisation" because for any results to be meaningful, it is
essential that all the apparatus used for the testing, produces
the same sets of results given all other parameters are equal.
There are many discussions about how good dissolution testing
may or may not be compared with the actual in-vivo effects, but
without a standardised test it is impossible to gain comparative
data.

The principle function of the dissolution test may be summarised

as follows:
 Optimisation of therapeutic effectiveness during product
development and stability assessment.
 Routine assessment of production quality to ensure uniformity
between production lots.
 Assessment of ‘bioequivalence’, that is to say, production of the
same biological availability from discrete batches of products from
one or different manufacturers.
 Prediction of in-vivo availability, i.e. bioavailability (where
applicable).

Dissolution testing was initially developed for oral dosage forms,

but the role of the test has now been extended to drug release
studies on various other forms such as topical and transdermal
systems and suppositories.
3. Apparatus 1 -
The Rotating
Basket
Adopted in 1970 the
rotating basket method
of dissolution testing
was the first official
method.

The apparatus consists

of a metallic drive shaft
connected to the
cylindrical basket. The
basket is positioned
inside a vessel made of
glass or other inert,
transparent material.
The temperature of the
media inside
the vessel is kept
constant by a water bath
or heating jacket. The
solution in the vessel is
stirred smoothly by the
rotating stirring element.

The diagram (left) shows

a simple graphic of the
rotating basket set-up.
This is very tightly
specified however and
the official drawing
according to the USP is
shown below.
The drawing shows
abasket manufactured
from mesh, connected to a basket hub of with a vent hole by the
use of clips. The Basket hub is connected to a rotating shaft.
Every parameter of those individual parts is specified.

The shafts and baskets must rotate freely and within specified
limits, and importantly, they must be accurately centered in the
vessel and be free from wobble. The validation of these
parameters will be covered in a later chapter.
The standard basket consists of a stainless steel 40 mesh
construction, but there are many variations depending on the
monograph and application. For example, suppository baskets
are manufactured from PTFE with vertical slits to facilitate
dissolution.

40 MeshSuppository
basket Basket

Mesh size refers to the number of openings per linear inch and
the diameter of the wire used to create the mesh is specified.
If the basket is reactive with the dosage form then it can be
coated with PTFE or an inert substance such as gold or titanium.
The diagram shows that the basket is connected to the rotating
shaft by use of clips onto a basket hub. The basket hub also has
a specific dimension and importantly, a small vent hole at the top
to allow air to escape from the basket should it become trapped.
It is important that this hole does not become clogged over time.
Some baskets are supplied for use without clips, and use a push-
on O-ring instead. While these are excellent for many
applications, it is important to show that the results from this
design are the same as the results obtained with clips - a
process known as equivalence. It is by no means guaranteed that
the results will be the same in every case.
It is also important to note that different dissolution tester
manufacturers will manufacture their baskets and hubs to
slightly different specifications but all within the USP guidelines.
Even though they look similar, baskets are not interchangeable
between different tester manufacturers. Labhut tightly controls
the manufacture of these items to ensure that they are
compatible with the stated bath.

4. Dissolution Baskets
Dissolution baskets are a precise and fragile piece of precision
instrumentation and are easily damaged.
The standard mesh size is 40 Mesh (40 openings per linear inch
of mesh), but many other sizes exist from 10 mesh, right up to
100 or 150 mesh which is incredibly fine and extremely delicate.
Meshes above this are generally not strong enough to support
the basket shape and integrity. Finer meshes are possible by
using a stronger supporting outer mesh..

150 Supp
10 20 40 100
Mes osito
Mesh Mesh Mesh Mesh
h ry
Bask Bask Bask Bask
Bask Bask
et et et et
et et

Mini baskets for small volume applications, and special baskets

for specific new drugs are also available.
There is a big variation in the quality of baskets available on the
market but there are a number of issues to look out for that can
make the difference between a short lifetime and long lifetime,
and also the ability of the basket to pass the calibration
procedures, particularly for wobble.

Simple Test - hold a basket rims between the thumb and

forefinger on both hands and gently twist back and forth. If there
is any movement in the mesh of the basket then there is a real
potential that the basket will easily deform, and worse, that it
will not pass the basket wobble test.

A good basket should be rigid with no movement. QLA/LabHut

baskets are manufactured from sintered mesh - mesh that has
been woven and then subjected to high temperature which
actually welds the wires together at each cross-over point. This
creates a rigid and non-moving mesh and will extend the life of
the baskets considerably. Because the baskets are rigid, they
will pass the wobble test far more easily.

Good baskets are reproducible baskets and reproducibility is the

goal of any dissolution testing..

Serialisation

Baskets should be individually serialised and

certified. Certification should always show the actual serial
number and not a generic certificate. This means that the
baskets are individually tested and QC tested to ensure that they
not only meet the USP specifications but that each individual
basket is correctly manufactured.
Serial numbers can be entered into the validation documents and
also ensure that the same baskets can be used in the same
vessel position every time.

Handling
Correct handling of baskets is important and avoids both
physical damage and contamination.

Baskets should only be handled by the rims and never piked up

by the mesh. Touching the mesh can not only deform it, but also
risks depositing oils and contamination from the hands. A dented
basket will also disrupt the media flow around the basket leading
to erroneous results and is definitely not permissable.

Cleaning
It is essential that baskets are kept clean. They should be rinsed
after use and if necessary a short time in an ultrasonic bath can
be used to dislodge particles which are blocking mesh holes.
Blocked mesh decreases media flow and can lead to lower
results. Baskets should then be dried prior to storage or re-use.
Never introduce a dosage form into a wet basket.

Storage

Baskets should also be stored properly and

not allowed to simply roll around a drawer where they can easily
be damaged and become mis-shapen.
The use of a simple basket storage rack, which is both
inexpensive and easy to use, is the best way to ensure that
baskets maintain their integrity during storage.
5. Apparatus 1 - Things to Think About

Common problems associated with the rotating

basket test

 Clogging
 Air Bubbles
 Excess Wobble
 Low Media Agitation
 Sampling Sensitivity

Clogging
The basket mesh can become blocked for a number of reasons,
including using the incorrect mesh size, blockage because of
gummy excipients (other ingredients which make up the tablet),
fast particulate release from the tablet, and air bubbles.

In all these cases the free flow of media through the basket can
become impeded, and that can have a direct effect on the rate of
dissolution. Observations should be made during the test to
identify when and if these problems are occurring.

Air Bubbles

Bubbles can be a problem with baskets.

When a basket is lowered into the media, there is a danger that
air bubbles can be trapped inside, or under the basket. The small
hole in the basket hub is supposed to release air trapped inside
but that does not always happen. (It is important to ensure that
the hole in the basket hub remains clean and free from any
blockage to enable air to escape).
Media degassing is not the issue in this case, but a bubble
trapped in or under the basket can easily invalidate the test. The
dosage form in the basket can float to the bubble, thus
preventing even dissolution. A bubble under the basket will
prevent media movement through the mesh and therefore will
have the same effect.
Trapped air is a symptom of wet or dirty baskets being lowered
into the medium, and if it does not dissipate immediately then
the test will need to be aborted.
Baskets manufactured from inferior materials or poorly made
can suffer more from this problem than good baskets.

Low Media Agitation

Given a perfect basket, shaft, vessel and media, the basket test
can be prone to generate remarkably little media movement,
particularly at low RPM. With a disintegrating tablet, particles
can clump together at the bottom of the media, an effect known
as coning.

There are numerous suggestions for avoiding this phenomenon

from peak shaped vessels to eliminating the basket test
altogether but none have been adopted by the USP thus far.
However, for the foreseeable future this remains a potential
issue, and any variations between vessel positions can have a
marked effect. All the more reason to ensure that good
baskets, vessels and shafts are used and that the physical
validation and visual inspection of the system is carried out
regularly. These areas will be covered in more detail later in this
article.

Sampling Sensitivity
Due to the low media agitation, there is the potential for
concentration gradients of active ingredient to be built up in the
vessel. Correct and reproducible sample position then becomes
important as well. This will be covered in more detail later.

6. Running the Test

A basic sequence of events takes place when running the
rotating basket test
 Inspect and Prepare the Dissolution Tester
 Prepare Media
 Deliver Media
 Check Temperature
 Prepare for Sampling
 Introduce Dosage Forms to Baskets
 Lower Baskets in Media
 Run Test
 Take Samples
 Measure Samples

Inspect and Prepare Dissolution Tester

The operator should prepare the tester for use, ensuring that all
parts are clean and dry and that there are no defects with any of
the parts. A defect includes scratches, bends, small dents etc.
It is a good idea to ensure that all baskets, shafts, vessels, etc,
remain in the same position for each test - it makes it easier to
identify issues should things go wrong.
All parts should be serialised and those numbers noted prior to
use. If any parts have been changed since the previous test then
those parts should be verified to fall within the guidelines.

Prepare Media
The media should be prepared according to the requirements,
and properly degassed using either the USP method, or another
suitable method to remove dissolved gas.
Degassing is particularly important with baskets since bubbles
will stick to rough surfaces first and baskets in particular.
Bubbles on basket mesh will impede media movement and affect
the test.

Deliver Media
Media should be the correct volume within 1% (all volumes are
measured at 20-25 degrees), and dispensed into the dissolution
vessel, taking great care to minimise the introduction of air or
agitate the media.
Volume measurement can be by weight, or by a suitable
calibrated volumetric flask. Measuring cylinders are sometimes
used but these are likely to be outside of the required accuracy
specification

Check the Temperature.

The temperature of the media should be 37 oC +/- 0.5oC. This
should be checked in each individual vessel and ideally the
temperature should be the same in all of them. Note that the
actual waterbath temperature may need to be set above 37 oC in
order to achieve the correct temperature inside the vessels. Note
also that lowering the baskets into the media will temporarily
decrease the media temperature by a small amount. It is
therefore a good idea to ensure that all vessels are actually at
37oC before the test begins and not lower.
If the media is going to stand for any length of time before the
test starts then cover the vessels with vessel covers to reduce
evaporation.
Prepare for Sampling
If manual sampling then prepare clean and dry sampling
cannulae, syringes and filters. Use only reproducible
and certified filters to avoid contamination issues and ensure
reproducibility. It is a good idea to use pure polypropylene
syringes (not those with a rubber tip plunger), or clean glass
syringes.
Prepare containers for samples, labelled for each vessel position.

Introduce Dosage Forms to Baskets

Place the dosage forms in the clean, dry baskets using forceps or
gloves. The dosage form should not have been left on the open
bench prior to this step, but stored in a suitable container to
prevent possible moisture interaction.
The basket with dosage form should be attached carefully to the
basket shafts, taking care not to bend the clips. Only handle the
baskets by the rim and not the mesh to avoid deforming the
basket.

Lower Baskets into Media

Without leaving the dosage forms in the baskets for an extended
period, start the test by lowering the baskets into the media. If
manual sampling, it may be necessary to stagger the start time
in order to accommodate the sampling time for each vessel.
Automated systems sample at the same time simultaneously and
therefore all baskets can be lowered together.
Inspect the baskets to ensure that no bubbles are trapped inside
or under them.
Record the start time for each basket to calculate the required
sampling time.

Run the Test

During the test is a good idea to visually inspect each test
position. It is often immediately obvious if there are problems
developing, and any observations should be noted to record
against possible concentration deviations later.
Take Samples
Samples are taken at the required time point within a 2%
window. This does not allow a lot of time if manual samples are
being taken - hence the need to stagger the start times. The
sample should be taken and filtered immediately - see sampling
section for sampling technique
and filtration.

Measure Samples
Once the samples have cooled,
measure according to the
defined analytical method. If
HPLC is to be used then the
samples may require an
additional filtration step before
that

Comments
A good and successful
dissolution test relies on
accurate preparation. If all else
is equal then if the preparation
is right then most test proceed
without any issues.

7. Apparatus 2 (The
Paddle )Test
The Rotating Paddle, although
Method 2, is actually the most
widely used method in
dissolution testing.
Originally developed by Poole
(1969) and was refined by
scientists at the FDA for Drug
Analysis in St Louis. The
specifications for Apparatus 2 are identical with those
for Apparatus 1 except that the paddle is substituted for the
rotating basket.
The dimensions of the paddle are closely controlled. Any
variations can easily have a detrimental effect on reproducibility
from vessel to vessel. For this reason, paddles should be treated
as a precision piece of equipment, stored correctly, and
inspected regularly for scratches, dents or other imperfections.
The dissolution test relies on uniform flow patterns and any
imperfections can lead to turbulent flow. For that same reason,
wobble and other deviations must be tightly controlled with
specifications similar to the basket test.

Serialisation
As with the basket test, the paddles should be individually
serialised, preferably with laser etching. If detachable paddles
and baskets are used - spin on/spin off paddles, then serialisation
should be on the shaft as well as the paddle section.

Allowable Variations

Poly fluorocarbon Coating

PTFE or other suitable coatings are permitted by the USP, and

have been widely used. The purpose of the coating is to reduce
the interaction between steel and the dosage form. As steel
quality improves, the need for coating reduces, but care should
be exercised to use paddles of suitable steel quality.
Poly fluorocarbon coating is a high temperature process and is
difficult to gain a consistent thickness over the paddle. Poor
coating and handling leads to flaking of the coating. This
exposes the steel but can also disrupt the flow with the rough
surface.
Re-coating is an expensive option and easily avoided by storing
the paddles in a suitable rack. Many users simply keep paddles
and baskets in a lab drawer - a sure recipe for a short life span.
Another alternative is to use a paddle manufactured from solid
PTFE or similar material. These paddles have the same
dimensions as the steel paddles specified by the USP, but
because they are solid, the coating cannot peel off.

8. Running the Paddle Test

The actual paddle test follows exactly the same procedure
as Running the Basket Test, except for the sample introduction.

Sample Introduction

Sample introduction for the paddle test is often the cause of

errors. Once again, the sample should not be left out on the open
bench for any length of time before it is used.

Unlike the basket test, the paddles will already be in position in

the vessels at the time the test starts. With this test however,
the sample is introduced with the paddle stationary - i.e. not
rotating. For a system where manual sampling is employed, with
a staggered time start, this can present some challenges with
some dissolution testers since the paddles will need to be
stopped one at a time.

If automated sampling is to be employed then the paddles can be

switched off, the samples introduced, and the paddles re-started.
Or an automated tablet dropping device can be used to drop the
tablets simultaneously.
So, why is it so important to have the paddles stationary? There
are two main reasons, both simply a point of practicality.
#1 If the tablet drops and the paddle is rotating, there is a good
chance that it will collide with the blade. If that happens, then
the tablet will probably be chipped, and the test will be
invalidated before it has even started.

#2 If the paddle and media is rotating, there is a good chance

that the tablet will not fall to the bottom of the vessel, but to one
side. This is particularly a problem with coated or sticky tablets
(and can happen without the media rotating also), but having
everything stationary reduces the risk.

9. References:
https://www.labhut.com/education-centre/about-dissolution-testing/dissolution-testing-education.html

https://www.pharmaguideline.com/2014/04/tablet-dissolution-test-in-different-stages-s1-s2-s3.html

http://www.pharmtech.com/dissolution-testing-3