2.9.3. Dissolution test for solid dosage forms EUROPEAN PHARMACOPOEIA 10.

vessel with a capacity of at least 12 L. The beaker is fitted with a of humidity. Examine the state of the samples after the period
slow stirrer and a device that will hold the cylinders vertically prescribed in the monograph. To pass the test all the samples
not less than 90 mm below the surface of the water and allow must have disintegrated.
them to be inverted without emerging from the water.
Method. Use three suppositories or pessaries. Place each one
on the lower disc of a device, place the latter in the sleeve
and secure. Invert the apparatuses every 10 min. Examine
the samples after the period prescribed in the monograph. To
pass the test all the samples must have disintegrated.

A. glass plate D. water

B. vaginal tablet E. dish, beaker

C. water surface

Figure 2.9.2.-2.

01/2016:20903

2.9.3. DISSOLUTION TEST FOR SOLID

DOSAGE FORMS(2)
This test is provided to determine compliance with the
dissolution requirements for solid dosage forms administered
orally. In this chapter, a dosage unit is defined as 1 tablet or
1 capsule or the amount specified.
APPARATUS
Apparatus 1 (Basket apparatus). The assembly consists
of the following : a vessel, which may be covered, made of
glass or other inert, transparent material(3) ; a motor ; a drive
shaft ; and a cylindrical basket (stirring element). The vessel is
partially immersed in a suitable water-bath of any convenient
size or heated by a suitable device such as a heating jacket.
The water-bath or heating device permits maintaining the
temperature inside the vessel at 37 ± 0.5 °C during the test
Figure 2.9.2.-1. – Apparatus for disintegration of suppositories and keeping the dissolution medium in constant, smooth
and pessaries motion. No part of the assembly, including the environment in
Dimensions in millimetres which the assembly is placed, contributes significant motion,
agitation, or vibration beyond that due to the smoothly
METHOD OF OPERATION FOR VAGINAL TABLETS rotating stirring element. Apparatus that permits observation
Use the apparatus described above, arranged so as to rest on of the preparation and stirring element during the test is
the hooks (see Figure 2.9.2.-2). Place it in a beaker of suitable preferable. The vessel is cylindrical, with a hemispherical
diameter containing water maintained at 36-37 °C with the bottom and a capacity of 1 L. Its height is 160-210 mm and its
level just below the upper perforated disc. Using a pipette, inside diameter is 98-106 mm. Its sides are flanged at the top.
adjust the level with water at 36-37 °C until a uniform film A fitted cover may be used to retard evaporation(4). The shaft
covers the perforations of the disc. Use three vaginal tablets. is positioned so that its axis is not more than 2 mm at any
Place each one on the upper plate of an apparatus and cover point from the vertical axis of the vessel and rotates smoothly
the latter with a glass plate to maintain appropriate conditions and without significant wobble that could affect the results. A
(2) This chapter has undergone pharmacopoeial harmonisation. See chapter 5.8. Pharmacopoeial harmonisation.
(3) The materials must not sorb, react, or interfere with the preparation to be tested.
(4) If a cover is used, it provides sufficient openings to allow ready insertion of the thermometer and withdrawal of samples.

326 See the information section on general monographs (cover pages)

EUROPEAN PHARMACOPOEIA 10.0 2.9.3. Dissolution test for solid dosage forms

speed-regulating device is used that allows the shaft rotation The flow-through cell (see Figures 2.9.3.-5 and 2.9.3.-6) of
speed to be selected and maintained at a specified rate, within transparent and inert material is mounted vertically, with a
± 4 per cent. filter system that prevents escape of undissolved particles
from the top of the cell ; standard cell diameters are 12 mm
Shaft and basket components of the stirring element are and 22.6 mm ; the bottom cone is usually filled with small
fabricated of stainless steel, type 316 or equivalent, to the glass beads of about 1 mm diameter, with 1 bead of about
specifications shown in Figure 2.9.3.-1. 5 mm positioned at the apex to protect the fluid entry tube ; a
tablet holder (see Figures 2.9.3.-5 and 2.9.3.-6) is available for
A basket having a gold coating of about 2.5 μm (0.0001 inch) positioning of special dosage forms. The cell is immersed in a
thick may be used. The dosage unit is placed in a dry basket water-bath, and the temperature is maintained at 37 ± 0.5 °C.
at the beginning of each test. The distance between the
inside bottom of the vessel and the bottom of the basket is
maintained at 25 ± 2 mm during the test.
Apparatus 2 (Paddle apparatus). Use the assembly from
Apparatus 1, except that a paddle formed from a blade and a
shaft is used as the stirring element. The shaft is positioned so
that its axis is not more than 2 mm from the vertical axis of the
vessel, at any point, and rotates smoothly without significant
wobble that could affect the results. The vertical center line
of the blade passes through the axis of the shaft so that the
bottom of the blade is flush with the bottom of the shaft. The
paddle conforms to the specifications shown in Figure 2.9.3.-2.
The distance of 25 ± 2 mm between the bottom of the blade
and the inside bottom of the vessel is maintained during
the test. The metallic or suitably inert, rigid blade and shaft
comprise a single entity. A suitable two-part detachable design
may be used provided the assembly remains firmly engaged
during the test. The paddle blade and shaft may be coated with
a suitable coating so as to make them inert. The dosage unit
is allowed to sink to the bottom of the vessel before rotation
of the blade is started. A small, loose piece of non-reactive
material, such as not more than a few turns of wire helix, may
be attached to dosage units that would otherwise float. An
alternative sinker device is shown in Figure 2.9.3.-3. Other
validated sinker devices may be used.
Apparatus 3 (Reciprocating cylinder). The assembly consists
of a set of cylindrical, flat-bottomed glass vessels ; a set of
glass reciprocating cylinders ; inert fittings (stainless steel
type 316 or other suitable material) and screens that are made
of suitable nonsorbing and nonreactive material, and that
are designed to fit the tops and bottoms of the reciprocating
cylinders ; a motor and drive assembly to reciprocate the
cylinders vertically inside the vessels, and if desired, index
the reciprocating cylinders horizontally to a different row
of vessels. The vessels are partially immersed in a suitable
water-bath of any convenient size that permits holding the
temperature at 37 ± 0.5 °C during the test. No part of the
assembly, including the environment in which the assembly is
placed, contributes significant motion, agitation, or vibration
beyond that due to the smooth, vertically reciprocating
cylinder. A device is used that allows the reciprocation
rate to be selected and maintained at the specified dip rate,
within ± 5 per cent. An apparatus that permits observation of
the preparations and reciprocating cylinders is preferable. The
vessels are provided with an evaporation cap that remains in
place for the duration of the test. The components conform
to the dimensions shown in Figure 2.9.3.-4 unless otherwise
specified.
Apparatus 4 (Flow-through cell). The assembly consists 1) Screen with welded seam : 0.22-0.31 mm wire
of a reservoir and a pump for the dissolution medium ; a diameter with wire opening of 0.36-0.44 mm.
After welding the screen may be slighty altered.
flow-through cell ; a water-bath that maintains the dissolution
medium at 37 ± 0.5 °C. Use the specified cell size. 2) Maximum allowable runout at “A” is 1.0 mm
when the part is rotated on center line axis with
basket mounted.
The pump forces the dissolution medium upwards through
the flow-through cell. The pump has a delivery range Figure 2.9.3.-1. – Apparatus 1, Basket stirring element
between 240 mL/h and 960 mL/h, with standard flow rates
of 4 mL/min, 8 mL/min, and 16 mL/min. It must deliver a Dimensions in millimetres
constant flow (± 5 per cent of the nominal flow rate); the flow The apparatus uses a clamp mechanism and 2 O-rings for the
profile is sinusoidal with a pulsation of 120 ± 10 pulses/min. fixation of the cell assembly. The pump is separated from
A pump without pulsation may also be used. Dissolution test the dissolution unit in order to shield the latter against any
procedures using the flow-through cell must be characterised vibrations originating from the pump. The position of the
with respect to rate and any pulsation. pump must not be on a level higher than the reservoir flasks.

General Notices (1) apply to all monographs and other texts 327
2.9.3. Dissolution test for solid dosage forms EUROPEAN PHARMACOPOEIA 10.0

A and B dimensions do not vary more than 0.5 mm when part is rotated on center line axis. Tolerances
are ± 1.0 mm unless otherwise stated.

Figure 2.9.3.-2. – Apparatus 2, Paddle stirring element

Dimensions in millimetres
Tube connections are as short as possible. Use suitably inert Assemble the apparatus, equilibrate the dissolution medium
tubing, such as polytetrafluoroethylene, with a 1.6 mm inner to 37 ± 0.5 °C, and remove the thermometer. ◊The test may
diameter and inert flanged-end connections. also be carried out with the thermometer in place, provided it
Apparatus suitability. The determination of suitability of is shown that results equivalent to those obtained without the
the apparatus to perform dissolution testing must include thermometer are obtained.◊
conformance to the dimensions and tolerances of the
apparatus as given above. In addition, critical test parameters
that have to be monitored periodically during use include
volume and temperature of the dissolution medium, rotation Place 1 dosage unit in the apparatus, taking care to exclude
speed (Apparatus 1 and 2), dip rate (Apparatus 3), and flow air bubbles from the surface of the dosage unit. Operate
rate of medium (Apparatus 4). the apparatus at the specified rate. Within the time interval
specified, or at each of the times stated, withdraw a specimen
Determine the acceptable performance of the dissolution test
from a zone midway between the surface of the dissolution
assembly periodically.
medium and the top of the rotating basket or blade, not less
PROCEDURE than 1 cm from the vessel wall. Where multiple sampling
times are specified, replace the aliquots withdrawn for analysis
APPARATUS 1 AND 2
with equal volumes of fresh dissolution medium at 37 °C or,
Conventional-release solid dosage forms where it can be shown that replacement of the medium is not
Procedure. Place the stated volume of the dissolution medium necessary, correct for the volume change in the calculation.
(± 1 per cent) in the vessel of the specified apparatus. Keep the vessel covered for the duration of the test and verify

328 See the information section on general monographs (cover pages)

EUROPEAN PHARMACOPOEIA 10.0 2.9.3. Dissolution test for solid dosage forms

the temperature of the medium at suitable times. Perform the Method B

analysis using a suitable assay method(5). Repeat the test with – Acid Stage. Place 1000 mL of 0.1 M hydrochloric acid in
additional dosage units. the vessel and assemble the apparatus. Allow the medium
If automated equipment is used for sampling or the apparatus to equilibrate to a temperature of 37 ± 0.5 °C. Place
is otherwise modified, verification that the modified apparatus 1 dosage unit in the apparatus, cover the vessel, and operate
will produce results equivalent to those obtained with the the apparatus at the specified rate. After 2 h of operation in
apparatus described in this chapter, is necessary. 0.1 M hydrochloric acid, withdraw an aliquot of the fluid,
Dissolution medium. A suitable dissolution medium is used. and proceed immediately as directed under Buffer stage.
The volume specified refers to measurements made between Perform an analysis of the aliquot using a suitable assay
20 °C and 25 °C. If the dissolution medium is a buffered method.
solution, adjust the solution so that its pH is within 0.05 units – Buffer stage. For this stage of the procedure use buffer
of the specified pH. Dissolved gases can cause bubbles to that has previously been equilibrated to a temperature of
form, which may change the results of the test. In such cases, 37 ± 0.5 °C. Drain the acid from the vessel and add 1000 mL
dissolved gases must be removed prior to testing(6). of pH 6.8 phosphate buffer, prepared by mixing 3 volumes
Time. Where a single time specification is given, the test of 0.1 M hydrochloric acid with 1 volume of a 0.20 M
may be concluded in a shorter period if the requirement solution of trisodium phosphate dodecahydrate R and
for minimum amount dissolved is met. Samples are to be adjusting, if necessary, with 2 M hydrochloric acid R or 2 M
withdrawn only at the stated times, within a tolerance of sodium hydroxide R to a pH of 6.8 ± 0.05. This may also be
± 2 per cent. accomplished by removing from the apparatus the vessel
containing the acid and replacing it with another vessel,
Prolonged-release solid dosage forms containing the buffer and transferring the dosage unit to
Procedure. Proceed as described for conventional-release the vessel containing the buffer. Continue to operate the
dosage forms. apparatus for 45 min, or for the specified time. At the end
Dissolution medium. Proceed as described for of the time period, withdraw an aliquot of the fluid and
conventional-release dosage forms. perform the analysis using a suitable assay method.
Time. The test-time points, generally 3, are expressed in hours. Time. All test times stated are to be observed within a
Delayed-release solid dosage forms tolerance of ± 2 per cent, unless otherwise specified.
Procedure. Use Method A or Method B. APPARATUS 3
Method A Conventional-release solid dosage forms
– Acid stage. Place 750 mL of 0.1 M hydrochloric acid in the Procedure. Place the stated volume of the dissolution medium
vessel, and assemble the apparatus. Allow the medium (± 1 per cent) in each vessel of the apparatus. Assemble the
to equilibrate to a temperature of 37 ± 0.5 °C. Place apparatus, equilibrate the dissolution medium to 37 ± 0.5 °C,
1 dosage unit in the apparatus, cover the vessel and operate and remove the thermometer. Place 1 dosage unit in each of
the apparatus at the specified rate. After 2 h of operation the reciprocating cylinders, taking care to exclude air bubbles
in 0.1 M hydrochloric acid, withdraw an aliquot of the fluid from the surface of each dosage unit, and immediately operate
and proceed immediately as directed under Buffer stage. the apparatus as specified. During the upward and downward
Perform an analysis of the aliquot using a suitable assay stroke, the reciprocating cylinder moves through a total
method. distance of 9.9-10.1 cm. Within the time interval specified, or
– Buffer stage. Complete the operations of adding the buffer at each of the times stated, raise the reciprocating cylinders
and adjusting the pH within 5 min. With the apparatus and withdraw a portion of the medium from a zone midway
operating at the rate specified, add to the fluid in the between the surface of the dissolution medium and the bottom
vessel 250 mL of a 0.20 M solution of trisodium phosphate of each vessel. Perform the analysis as directed. If necessary,
dodecahydrate R that has been equilibrated to 37 ± 0.5 °C. repeat the test with additional dosage units.
Adjust, if necessary, with 2 M hydrochloric acid R or 2 M Replace the aliquot withdrawn for analysis with equal volumes
sodium hydroxide R to a pH of 6.8 ± 0.05. Continue to of fresh dissolution medium at 37 °C or, where it can be shown
operate the apparatus for 45 min, or for the specified time. that replacement of the medium is not necessary, correct for
At the end of the time period, withdraw an aliquot of the volume change in the calculation. Keep the vessel covered
the fluid and perform the analysis using a suitable assay with the evaporation cap for the duration of the test and verify
method. the temperature of the medium at suitable times.

A : acid-resistant wire clasp B : acid-resistant wire support

Figure 2.9.3.-3. – Alternative sinker
Dimensions in millimetres
(5) Test specimens are filtered immediately upon sampling unless filtration is demonstrated to be unnecessary. Use an inert filter that does not cause adsorption of the active substance or
contain extractable substances that would interfere with the analysis.
(6) A method of deaeration is as follows : heat the medium, while stirring gently, to about 41 °C, immediately filter under vacuum using a filter having a porosity of 0.45 μm or less, with
vigorous stirring, and continue stirring under vacuum for about 5 min. Other validated deaeration techniques for removal of dissolved gases may be used.

General Notices (1) apply to all monographs and other texts 329
2.9.3. Dissolution test for solid dosage forms EUROPEAN PHARMACOPOEIA 10.0

Dissolution medium. Proceed as described for

conventional-release dosage forms under Apparatus 1 and 2.
Time. Proceed as described for conventional-release dosage
forms under Apparatus 1 and 2.

Prolonged-release dosage forms

Procedure. Proceed as described for conventional-release
dosage forms under Apparatus 3.
Dissolution medium. Proceed as described for
prolonged-release dosage forms under Apparatus 1 and 2.
Time. Proceed as described for prolonged-release dosage
forms under Apparatus 1 and 2.

Delayed-release dosage forms

Procedure. Proceed as described for delayed-release dosage
forms, Method B, under Apparatus 1 and 2, using one row
of vessels for the acid stage media and the following row of
vessels for the buffer stage media, and using the volume of
medium specified (usually 300 mL).
Time. Proceed as directed for delayed-release dosage forms
under Apparatus 1 and 2.

APPARATUS 4
Conventional-release dosage forms
Procedure. Place the glass beads into the cell specified. Place
1 dosage unit on top of the beads or, if specified, on a wire
carrier. Assemble the filter head and fix the parts together
by means of a suitable clamping device. Introduce by the
pump the dissolution medium warmed to 37 ± 0.5 °C through
the bottom of the cell to obtain the flow rate specified and
measured with an accuracy of 5 per cent. Collect the eluate by
fractions at each of the times stated. Perform the analysis as
directed. Repeat the test with additional dosage units.
Dissolution medium. Proceed as described for
conventional-release dosage forms under Apparatus 1 and 2.
Time. Proceed as described for conventional-release dosage
forms under Apparatus 1 and 2.

Prolonged-release dosage forms

Procedure. Proceed as described for conventional-release
dosage forms under Apparatus 4.
Dissolution medium. Proceed as described for
conventional-release dosage forms under Apparatus 4.
Time. Proceed as described for conventional-release dosage
forms under Apparatus 4.

Delayed-release dosage forms

Procedure. Proceed as described for delayed-release dosage
forms under Apparatus 1 and 2, using the specified media.
Figure 2.9.3.-4. – Apparatus 3, glass vessel and reciprocating
Time. Proceed as described for delayed-release dosage forms cylinder
under Apparatus 1 and 2. Dimensions in millimetres

330 See the information section on general monographs (cover pages)

EUROPEAN PHARMACOPOEIA 10.0 2.9.3. Dissolution test for solid dosage forms

INTERPRETATION the 3 levels unless the results conform at either S1 or S2.

Conventional-release solid dosage forms The quantity Q, is the specified amount of dissolved active
substance, expressed as a percentage of the labelled content ;
Unless otherwise specified, the requirements are met if the the 5 per cent, 15 per cent, and 25 per cent values in the Table
quantities of active substance dissolved from the dosage units are percentages of the labelled content so that these values
tested conform to Table 2.9.3.-1. Continue testing through and Q are in the same terms.

Figure 2.9.3.-5. – Apparatus 4, large cell for tablets and capsules (top), tablet holder for the large cell (bottom)
Dimensions in millimetres unless otherwise specified

General Notices (1) apply to all monographs and other texts 331
2.9.3. Dissolution test for solid dosage forms EUROPEAN PHARMACOPOEIA 10.0

Table 2.9.3.-1 Prolonged-release dosage forms

Level Number Acceptance criteria Unless otherwise specified, the requirements are met if the
tested quantities of active substance dissolved from the dosage units
S1 6 Each unit is not less than Q + 5 per cent. tested conform to Table 2.9.3.-2. Continue testing through
S2
the 3 levels unless the results conform at either L1 or L2.
6 Average of 12 units (S1 + S2) is equal to or greater than Q,
and no unit is less than Q − 15 per cent. Limits on the amounts of active substance dissolved are
S3 12 Average of 24 units (S1 + S2 + S3) is equal to or greater
expressed in terms of the percentage of labelled content. The
than Q, not more than 2 units are less than Q − 15 per limits embrace each value of Qi, the amount dissolved at each
cent, and no is less than Q − 25 per cent. specified fractional dosing interval. Where more than one
range is specified, the acceptance criteria apply individually
to each range.

Figure 2.9.3.-6. – Apparatus 4, small cell for tablets and capsules (top), tablet holder for the small cell (bottom)
Dimensions in millimetres unless otherwise specified

332 See the information section on general monographs (cover pages)

EUROPEAN PHARMACOPOEIA 10.0 2.9.4. Dissolution test for transdermal patches

Table 2.9.3.-2 1. DISK ASSEMBLY METHOD

Level Number Acceptance criteria Equipment. Use the paddle and vessel assembly from the
tested paddle apparatus described in the dissolution test for solid
L1 6 No individual value lies outside each of the stated ranges oral dosage forms (2.9.3) with the addition of a stainless steel
and no individual value is less than the stated amount at
the final test time. disk assembly (SSDA) in the form of a net with an aperture of
L2 6 The average value of the 12 units (L1 + L2) lies within each
125 μm (see Figure 2.9.4.-1).
of the stated ranges and is not less than the stated amount
at the final test time ; none is more than 10 per cent of
labelled content outside each of the stated ranges; and
none is more than 10 per cent of labelled content below
the stated amount at the final test time.
L3 12 The average value of the 24 units (L1 + L2 + L3) lies within
each of the stated ranges, and is not less than the stated
amount at the final test time; not more than 2 of the
24 units are more than 10 per cent of labelled content
outside each of the stated ranges ; not more than 2 of the
24 units are more than 10 per cent of labelled content
below the stated amount at the final test time; and none
of the units is more than 20 per cent of labelled content
outside each of the stated ranges or more than 20 per cent
of labelled content below the stated amount at the final
test time.
Delayed-release dosage forms
Acid stage. Unless otherwise specified, the requirements of
this portion of the test are met if the quantities, based on the
percentage of the labelled content of active substance dissolved
from the units tested conform to Table 2.9.3.-3. Continue
testing through the 3 levels unless the results of both acid and
buffer stages conform at an earlier level.
Table 2.9.3.-3
Level Number Acceptance criteria
tested
A1 6 No individual value exceeds 10 per cent dissolved.
Figure 2.9.4.-1. – Disk assembly
A2 6 The average value of the 12 units (A1 + A2) is not more
than 10 per cent dissolved, and no individual unit is The SSDA holds the system at the bottom of the vessel and is
greater than 25 per cent dissolved. designed to minimise any dead volume between the SSDA and
A3 12 The average value of the 24 units (A1 + A2 + A3) is not the bottom of the vessel. The SSDA holds the patch flat, with
more than 10 per cent dissolved, and no individual unit is the release surface uppermost and parallel to the bottom of the
greater than 25 per cent dissolved.
paddle blade. A distance of 25 ± 2 mm between the bottom of
Buffer stage. Unless otherwise specified, the requirements the paddle blade and the surface of the SSDA is maintained
are met if the quantities of active substance dissolved from during the test (see Figure 2.9.4.-2). The temperature is
the units tested conform to Table 2.9.3.-4. Continue testing maintained at 32 ± 0.5 °C. The vessel may be covered during
through the 3 levels unless the results of both stages conform the test to minimise evaporation.
at an earlier level. The value of Q in Table 2.9.3.-4 is 75 per
cent dissolved unless otherwise specified. The quantity, Q,
is the specified total amount of active substance dissolved in
both the acid and buffer stages, expressed as a percentage of
the labelled content. The 5 per cent, 15 per cent and 25 per
cent values in the Table are percentages of the labelled content
so that these values and Q are in the same terms.
Table 2.9.3.-4
Level Number Acceptance criteria
tested
B1 6 No unit is less than Q + 5 per cent.
B2 6 The average value of the 12 units (B1 + B2) is equal to or
greater than Q, and no unit is less than Q − 15 per cent.
B3 12 The average value of the 24 units (B1 + B2 + B3) is equal
to or greater than Q, not more than 2 units are less than
Q − 15 per cent, and no unit is less than Q − 25 per cent.
Recommendations on dissolution testing are given in general
chapter 5.17.1.

01/2008:20904

Figure 2.9.4.-2. – Paddle and disk

2.9.4. DISSOLUTION TEST FOR Procedure. Place the prescribed volume of the dissolution
TRANSDERMAL PATCHES medium in the vessel and equilibrate the medium to the
prescribed temperature. Apply the patch to the SSDA,
This test is used to determine the dissolution rate of the active ensuring that the release surface of the patch is as flat as
ingredients of transdermal patches. possible. The patch may be attached to the SSDA by a

General Notices (1) apply to all monographs and other texts 333