USP Dissolution Apparatus IV:

Flow-Through Cell

Presented By:
Darshani Kansara
(1 Year M.Pharm., Pharmaceutics,
st
Bombay College of Pharmacy)
 Background
Introduced and
extensively studied by
Langenbucher.

Included officially in the

USP as Apparatus IV, in
a supplement to
USPXXII, in1990.
Principle
A sample is restrained
in a small-volume cell
and subjected to stream
of dissolution media.
Special pulsating
movement of piston
pump obviates need for
further stirring and/or
shaking elements.
 Design and Working
The assembly consists of a reservoir and a
pump for the dissolution medium; a flow-
through cell; and a water bath.
 The flow-through cell is
made up of transparent and
inert material, cylindrical in
shape, mounted vertically.
The pump forces constant
flow of dissolution medium
upwards(from bottom to
top) through the flow-
through cell.
The cell is provided with a
filter system at top of the
cell, that prevents escape of
undissolved particles from
the top of the cell and
provides a clear solution for
subsequent assay.
 The bottom cone is
usually filled with small
glass beads of about 1-
mm diameter with one
large bead of about 5 mm
positioned at the apex to
protect the fluid entry
tube.
A tablet holder is
available for positioning
of special dosage forms.
The cell is immersed in a
water bath, and the
temperature is
maintained at 37 0.5 C.
 Closed Compartment
Model

The flow-through cell can be of closed or open type, depending on

whether the effluent returns back to the source or not.
The closed type system would conserve medium, continuing to
recycle the testing liquid v/s open system, uses a copious amount of
medium for the test.

Open Compartment
Model
 The experimental design of the closed systems
results in cumulative dissolution profiles.
Whereas, with the open systems, all drug
dissolved is instantaneously removed along the
flow of the dissolution medium.
The results are therefore generated in the form of
dissolution rates, i.e., fraction dissolved per time
unit. The results obtained from tests in the flow-
through system therefore need to be transformed
in order to present the data in the usual form,
i.e., dissolution profiles of cumulative amount
dissolved vs. time.
 Types of Cell

TABLET TABLET POWDERS IMPLANTS SUPPOSITORIES OINTMENTS

12mm 22.6mm AND AND SOFT AND
GRANULES GELATIN CREAMS
CAPSULES
 Advantages
Useful for various dosage forms
Maintenance of sink conditions
Ideal hydrodynamics
Convenience of changing pH and dissolution media
Dosage form positioning
= Principle of their operation is more physiologically
relevant.
In-built filtration
Easy and continuous sampling
Minimizing downtime between tests
 Useful for Various Dosage Forms
Other USP apparatus can
not be used for a variety
of dosage forms
produced now-a-days,
particularly special
dosage forms. Also, they
cannot cover all desired
dissolution studies.
Specially designed
models of flow-through
cell are available for
various dosage forms
and covers almost all
dosage forms.
 Maintenance of Sink Conditions
The maintenance of sink conditions is
especially critical in case of drugs with poor
solubility.
The closed compartment apparatus uses a
limited volume of dissolution medium and
thus, do not provide sink conditions.
The flow-through cell provides sink conditions
by supplying an unlimited quantity of fresh
dissolution medium.
 Ideal hydrodynamics
Flow-through cell offers ideal hydrodynamic conditions for
mild agitation, homogeneity and a definable solvent
(dissolution medium) flow pattern (laminar flow), which
can be controlled.
No stirring, all the problems of wobbling, shaft eccentricity,
vibration, stirrer position, coning etc. dont exist.
Easy sampling due to homogeneity of the dissolution
medium in the cell.
Only a small number of apparatus parameters will affect
the test.
Flow rates in vitro can be varied with time using
appropriate pumps and control software, in order to reflect
the in-vivo conditions of dissolution.
 Convenience of Changing pH and
Dissolution Media
pH and media changes are critical for dissolution
testing of some products, eg.ER products.
In an open loop flow-through cell, a media
selector allows pH changes after a predetermined
time without movement of the dosage form.
Unlike other apparatus where physical movement
must be made to move the dosage to the next
media, which is very time consuming and tedious.
The flow-through cell method is the only method
that allows for a media change for dosage forms
like suspensions, granules and powders.
Open system for pH changes
 In-Built filtration
Filtration of the dissolution sample aliquot is usually
needed prior to quantitation. Filtration of the
dissolution samples is usually necessary to prevent
undissolved drug particles from entering the analytical
sample and dissolving further. Also, filtration removes
insoluble excipients that may otherwise cause a high
background or turbidity.
Filter system at top of the cell will filter the dissolution
medium in such a way that undissolved particles goes
back in the cell, gives more accurate results.
No need of additional step of filtration or
centrifugation.
Dosage Form Positioning
Dosage forms can be
simply placed in the cell,
positioned uniformly in a
tablet clip holder or
placed on glass beads.
This can eliminate
variables caused by
introduction of a tablet to
a vessel, tablet sticking,
swelling and floating.
Numerous possibilities in
positioning the dosage
form is available.
 Disadvantages
Preparation and cost of large volume of dissolution medium in
case of open type of flow-through cell. Maintenance of
specific flow rates requires use of expensive pumps.
Temperature control is difficult to achieve in column type flow
through system than in the conventional stirred vessel type.
Tendency of the filter to clog because of the unidirectional
flow.
Different types of pumps, such as peristaltic and centrifugal,
have been shown to give different dissolution results.
Closed systems measure cumulative dissolved drug , whereas
open systems measure the amount dissolved within specific
time intervals (differential amount dissolved).
Todays Evolution of Flow-Through Cell
New developments in the flow-through cell
method include the design of a T-Cell to study
SR parenteral dosage forms where drug is
transported via both a diffusion and
convection process in vitro without the use of
a membrane.
Other new developments include holding
devices for dialysis bags and contact lenses.
CE7 SMART FTP with two cell
 References:
Sinko Patrick J., Martin's Physical Pharmacy and
Pharmaceutical Sciences, Sixth Edition, Chapter 13, Page 300-
317.
Dressman Jennifer J., Kramer Johannes, Pharmaceutical
Dissolution Testing, Chapter 1 and 2, Page 1-68.
Banakar Umesh V., Pharmaceutical Dissolution Testing,
Chapter 3, Page 53-100.
United States Pharmacopoeia, Chapter 711.
Thank You!