IN-VITRO DISSOLUTION

TESTING
Dissolution and drug release tests are in-vitro tests that measure
the rate and extent of dissolution or release of the drug substance
from a drug product, usually aq.medium under specified
conditions.
I t is an important QC procedure for the drug product and linked to
product performance in-vivo.

NEED FOR DISSOLUTION TESTING:

>Evaluation of bioavailability.
Batch to batch drug release uniformity.
efficacious and therapeutically optical
Development
dosage forms.
of more
Ensures quality and stability of the product.
Product development, quality control, research and application.
IN-VITRO DISSOLUTION TESTING MODELS
Non-Sink methods
& 1) NATURAL CONVECTIONNON SINK METHODS:
a ) Klein solvmeter method
b) Nelson hanging pellet method
Levy static disk method

2 ) FORCED CONVECTION NON SINK METHODS:

a) Tumbling method
>b) Levy or Beaker method
Rotating disk method
d ) Particle size method
e)USP Rotating basket apparatus
) f) USPPaddle apparatus
 Sink methods
R 3) FORCED CONVECTION SINK DEVICES:
a) Wurster pollis adsorptionmethod
b) Partition method
c)Dialysis method s
d) Rotating disk apparatus
a 4) CONTINOUS FLOw/FLOW THROUGH METHODS:
a ) Pernarowski method
b) Langenbucher method
)Baun and Walker
d ) Tingstad and Reigelman
e ) Modified column apparatus
9 Takenaka method
 NATURAL CONVECTION NONSsINK METHOD
In this method the density difference is utilized
for replacing the surrounding dissolution medium'

Klein Solvmeter method

Carrier device surrounded by flat
and is immersed in dissolution
medium
When dosage form is placed in the
boat the bar moves and as dosage
form dissolves it moves upwards
Amount of dosage form dissolved
is revealed from the difference in
height of bar movement

Nelson hanging pellet method:

Aluminum strip having provision for holding

dosage form which is in turn connected
perfectly maintained
balance arm of strip
Dosage form is mounted on aluminium strip
with help of wax .this method can be
employed to know Intrinsic dissolution rate.
To prevent disintegration further
pressures can be applied and also constant
high
surtace.
 Levy static Disk method
Acrylic holder containing dosage form is inserted into a
known volume of medium through rubber stopper
The vial is inverted and placed in incubator at 37 C At
specific time intervals the vial is removed from
incubator and samples are analysed
Disadvantages :- effect of conc. On dissolution medium
is ignored and the surface area of dosage form while
dissolving is assumed constant which is not impractical.

a. Tumbling Method:
The Drug/ Dosage form with the
dissolution medium is placed in test tube
that is in turn clamped to the revolving
drum which is rotated at the speed of 6-
12rpm in water bath at 37 C
The test tubes are removed and the
medium is assayed at regular time points
for the dissolved drug amount

b. Beaker method
Reported by Levy and Hayes(1960)
Dissolution medium, 250ml of 0.1N HCl at 37°C placed
in a 400ml beaker.
Agitation by three blade polyethylene stirrer,5cm
diameter and rotates at 60 rpm.
Stirrer immersed to a depth of 2.7 cm in medium and in
the center.
Tablets are placed in a beaker and test was carried out.
Samples are removed and assayed for the content.
 c. Rotating disk method
Developed by late Eino nelson and described by Levy and Sahli.
I n this method,the drug is compressedin a non-disintegrating disc
without excipients.
The disc is mounted in a holder so that only one face ofthe disc is
exposed to the dissolution medium.
The holder and disc are immersed in medium and held in a fixed
position as in static disc method and rotated at a given speedin
rotating disc method.

Samples are collected at predetermined times.

Surface area of the drug through which dissolution
occurs is kept constant -intrinsic dissolution rate.

)Roting dec mehod

Sic c meod

d. USP ROTATING BASKET

DESIGN:
Vessel: -Made of borosilicate glass.
-Semi hemispherical bottom
-Capacity 100ml
Shaft: -Stainless steel 316
-Rotates smoothly without
significance wobble(100 rpm)
-Speed regulator Dosage Form
Water bath:-Maintained at 37+0.5°C
USE: Tablets, capsules, delayed release
suppositories, floating dosage forms.
 Advantages
Full pH change during the test
Can be easily automated
which is important for routine
investigations.

Disadvantages -
Basket screen is clogged with
gummy particles.
Hydrodynamic,dead zone"
under the basket
Degassing is particularly
important
Mesh gets corroded by HCl solution.

e. USP paddle apparatuS

DESIGN:
Vessel: -Same as basket apparatus
Shaft:-The blade passes through the
shaft so that the bottom of the blade
fuses with bottom of the shaft.
Stirring elements: -Made of teflon
For laboratory purpose
-Stainless steel 316
Water-bath: -Maintains at 37+0.5°C
Sinkers: -Platinum wire used to
prevent tablet/capsule from floating
Advantages
Easy to use

Robust

pH change possible
Can be easily automated which is important for
routine investigations

Disadvantages
pH/media change is often difficult
Hydrodynamics are complex, they vary with site ofthe dosage form in
the vessel (sticking.floating) and therefore maysignificantly affect
drug dissolution

Sinkers for floating dosage forms Sooy

PEEN

Forced Convection Sink Devices:

An ideal dissolution process is one which will mimic the invivo

onditions by maintaining perfect sink conditions. these perfect sink

conditions can be maintained by either of the following systems:
a) Fixed fluid volune.
b) Multiple phase
c) Continuous fluid flow
A. Wurster-Polli Adsorption Method
In this method the dissolved drug is
adsorbed by charcoal or bentonite.
care should be taken regarding the
adsorbent, adsorbent should not alter the
viscosity of the medium

B.Partition Method:
In this device organic phase is employed to
remove the dissolved drug such that the
drug would partition between the
lipophilic and hydrophilic phases.
selection of organic phase plays a critical 24

role.
C. Dialysis Method:

Cell consist of 32mm inflated membrane.

>Plugged at the lower end by tight fitting cylindrical
perspex box.
Upper end of the tube held by thin perspex ring inserted
into the tube and secured by an elastic band.
The cell suspended, from the arm of the tablet
disintegration apparatus and containing the dosage form
in 150ml of distilled water at 37°C.
The cell is raised or lowered 30times a min, into 150ml of
distilled water at same temperature.
Agitation by slight flexing and stretching of the dialysis
membrane as it enters and leaves the bath. Rotated at
60rpm.

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Broen arrows indicate irecion ol soiute vansfer

(a) (D)
Fig. 3.16 Schematic illustration of a forced-convection sink dissolution testing
method: dialysis devices using (a) rotating cel. (b) rotating flask and external dialysis,
and ic) oscillatung cell

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D. Rotating Flask apparatus:
R In this method a flask containing dissolution medium is rotated around
its horizontal axis ina water bath kept at a temperature of 37 C
The flask has a provision of sampling such that aliquots can be
withdrawn and the fresh medium can be replaced back.
R This apparatus is best suited for oral solid dosage forms like tablets and
capsules since they do not require much agitation.

(a (b) (c)

Flg. 3.17 Schematic illustration of a orced-conecion sink dissclutun Sting

method rotat1ng lask dev:ces by (a) Ferrari and Khuty, (b) Gibaldi and r i t rau
d (c) Koch
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Flow Through Devices

For the drugs which saturate rapidly in large

volumes of medium, USP apparatus will not serve the
purpose.
F o r this the suitable device is flow through device. In
this device unlimited quantity of fresh dissolution is
available.
RA dosage form is placed in a small cell and is subjected
to a stream of fresh dissolution media.
4. CONTINUOUS FLOW APPARATUS BY PERNAROWSKI
It consists of 10 mesh stainless steel basket stirrer assembly with an
adjustable stirrer.
Rthe chamber is 3 necked flask of 33 mm and the rest two of 20 mm
diameter.
a 1L of medium is employed within the flask. the dissolution
characteristics are dependent upon the amypa4ÁHaedium pumped
throug5thingdsbaft-
Type 2 fluid
Suction tob Two way stopper
sampling

Glass tube

basket

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B.LANGENBUCHER COLUMN-TYPE FLOWN

THROUGH METHOD:
This device is according to the dissolution basicc
design.
R The screen is constructed such that the medium
flows equally through the entire cross section in a
laminar pattern.
R This is again closed by a secondary screen, filter
which prevents the undissolved drug from being
eluted.
cONTINUOUS FLOW APPARATUS BY TINGSTAD AND
RIEGELMAN:
R acylindrical glass cell of 6.1 cm long and 1.9 cm in diameter constructed
with two glass filter funnels is used.
The dissolution cell has filter membranes which prevents the solid
particles from being analyzed.
Ca There are also external valves to control the excess flow of solvent into
the system. the air trap averts air bubbles.
R The complete as bath kept at 37 C.
AL Trap

TO Anal>y s e r

D ion

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FLOW-THROUGH MODIFIED COLUMN APPARATUS:

R The device consists of filter of 14 M -size made of nylon.
t h e tubing from the pump is connected to the dissolution cell.
t h e Teflon faced stainless steel supports the screen resting on the bottom
half of the filter holder.
aThe direction of the flow is such that the particles do not fall through
the screern. the rest of the process is the same.

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CONTINUOUS FLOW APPARATUS BY TAKENAKA
& The release of drug is measured with the aid of in vitro
simulator device consisting of flow type dissolution
container.
The dosage form is placed in the basket rotating at 94
rpm with 300 ml of medium.
R then the medium is removed by collecting reservior
using peristaltic pump.
R aliquots are withdrawn using syringe and then filtered
using Whatman filter paper and the same volume is
replaced immediately with fresh medium.

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Flg. 3.25 SchematiC illusiration of a llow.-thruugh dswiuliun tersg*T

naka et al. A, Simulated intestinal fuid reservoir, 3 peristal:ie punp. ( i onli
COiainicr. D, watcrbath; E, collecting reservoir; F, motor: G. pH cleciroJes; H, ih.

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