Dissolution Testing

Sarika Wairkar
 Dissolution

 Dissolution is defined as the process by which

a solid substance enters in a solvent to yield
solution.

 Fundamentally it is controlled by the affinity

between the solid substances and the solvent.
 Dosage forms to be tested
• Immediate release dosage forms
• powders, granules / beads, tablets, capsules

• Controlled release dosage forms

• powders, granules / beads, tablets, capsules

• Transdermal systems
• Implants

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 Need of Dissolution and Drug Release Testing

 The dissolution test is an important quality control procedure for the drug
product and is often linked to product performance in vivo. It measure the
rate and extent of dissolution or release of the drug substance from a drug
product in dissolution medium under specified conditions.

 The USP-NF (United States Pharmacopeia) sets standards for dissolution

and drug release tests of most drug products. Ideally, the dissolution
method used for a particular drug product in vitro relates to the
bioavailability of the drug in vivo.

As a quality control test, dissolution and drug release testing may be used for:
 Batch-to-batch drug release uniformity
 Stability
 Predicting in-vivo performance
 A dissolution test demonstrates that a dosage form is capable of releasing
its drug into solution at an acceptable rate and to an acceptable extent.
 Advantages of dissolution testing
 A dissolution test demonstrates that a dosage form
is capable of releasing its drug into solution at an
acceptable rate and to an acceptable extent.

 For sparingly soluble drugs a dissolution test is a

better dosage form performance indicator than a
disintegration test.

 Dissolution tests are more sophisticated dosage

form performance tests than disintegration tests
but they are far more complicated and much more
expensive to perform.
 Detention of the dissolution rates from solid
dosage forms under standardised conditions
several factors are to be considered such as

 Physical characteristics of the dosage form.

 Wettability of the dosage unit.

 Penetration ability of the dissolution medium.

 Swelling process.

 Disintegration & disaggregation of the dosage

form.
 Tab/Capsule Disintegration Granules Disaggregation Fine particles
or
Aggregates
Dissolution

Dissolution
Dissolution

Drug in solution
(in-vivo – in-vivo
(in-vivo ABSORPTION

DRUG IN BLOOD AND

OTHER TISSUES
Rate of dissolution of the drug can become the rate-limiting step before
the drug appears in the blood.
Official Dissolution Monographs

 United States Pharmacopeia

 British Pharmacopoeia
 Indian Pharmacopoeia

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Dissolution Conditions

 Dissolution apparatus
 different media (including volume and pH
of medium)
 Agitation rates
 Temperature
 Time points
 Dissolution volume and pH
 The usual volume of the medium is 500–1000 mL. Drugs
that are poorly water soluble may require use of a very-
large-capacity vessel (up to 2000 mL) to observe significant
dissolution. In some cases, 1% sodium lauryl sulfate (SLS)
may be used as the dissolution medium for water-insoluble
drugs.

 Sink conditions is a term referring to an excess volume of

medium that allows the solid drug to dissolve continuously.
If the drug solution becomes saturated, no further net drug
dissolution will take place. According to the USP-NF, "the
quantity of medium used should be not less than 3 times
that required to form a saturated solution of the drug
substance."

 Solubility of the API in water, other media like 0.1 N HCl,

or buffers (pH 4.5/6.8/7.2/7.8) of different pH should be
considered.
 Agitation Rates, Temperature and
Time points
 The amount of agitation and the nature of the stirrer
affect hydrodynamics of the system, thereby affecting
the dissolution rate. (50/75/100 RPM)

 The temperature of the dissolution medium must be

controlled, and variations in temperature must be
avoided. Most dissolution tests are performed at 37°C.

 Time points to be considered based on dosage form

requirements.
Interpretation of Dissolution
Conventional-release (or immediate-release) dosage forms
 Unless otherwise specified in the individual monograph the
requirements are met if the quantities of active ingredient(s)
dissolved from the dosage forms tested conform to below Table.

 Continue testing through the three levels unless the results

conform at either S1 or S2. The quantity, Q, is the specified
amount of dissolved active ingredient expressed as a
percentage of the labelled content; the 5%, 15% and 25%
values in the acceptance table are percentages of the labelled
content so that these values and Q are in the same terms.
Official Dissolution Tests- USP

1. Rotating Basket
2. Paddle
3. Reciprocating Cylinder
4. Flow Through Cell
5. Paddle Over Disk
6. Rotating Cylinder
7. Reciprocating Holder
 Official Dissolution Tests-
British Pharmacopoeia
 The BP provides specifications for three different
dissolution apparatuses:

– Apparatus I (Basket apparatus) (also known as "rotating

basket method")
– Apparatus II (Paddle apparatus)
– Apparatus III (Flow-through cell apparatus)

The BP directs that Apparatus I is to be used unless

otherwise directed.
 Dissolution Apparatus I
(Basket apparatus)
 In this apparatus the dosage form to be tested is placed in a closed
cylindrical basket made of fine stainless steel mesh or cloth, the top
of which is attached to a shaft driven by a motor.

 This assembly (ie. the drive shaft with attached cylindrical basket)
is positioned vertically within the centre of a much larger
transparent cylindrical vessel with a hemispherical bottom (the
"dissolution vessel") which contains the dissolution medium and is
rotated at a specified rate (usually 100 r.p.m.) by the motor. The
dissolution vessel is immersed in a water bath that will maintain
the dissolution medium at 37°C.

 Apparatus 1 is generally preferred for capsules and for dosage

forms that tend to float or disintegrate slowly.
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Dissolution Apparatus I (Basket apparatus) BP
(Dimensions in mm)

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 Dissolution Apparatus II
(Paddle apparatus)
 This is the second of three official dissolution apparatuses
described in the BP. It is defined by the BP as follows:

 "Use Apparatus I described above, except that in the

stirring element the basket is replaced by a paddle ... . The
blade passes through the diameter of the shaft so that the
bottom of the blade is flush with the bottom of the shaft.
The shaft is positioned so that its axis is within 2 mm of
the axis of the vessel and the lower edge of the blade is 23
to 27 mm from the inside bottom of the vessel. The
apparatus operates in such a way that the paddle rotates
smoothly and without significant wobble."
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Dissolution Apparatus II
(Paddle apparatus) BP

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 Paddle Method (Apparatus 2)

 The paddle apparatus (Apparatus 2) consists of a special, coated

paddle that minimizes turbulence due to stirring. The paddle is
attached vertically to a variable-speed motor that rotates at a
controlled speed. The tablet or capsule is placed into the round-bottom
dissolution flask, which minimizes turbulence of the dissolution
medium. The apparatus is housed in a constant-temperature water bath
maintained at 37°C, similar to the rotating-basket method.

 The most common operating speeds for Apparatus 2 are 50 rpm for
solid oral dosage forms and 25 rpm for suspensions. Apparatus 2 is
generally preferred for tablets.

 A sinker, such as a few turns of platinum wire, may be used to prevent

a capsule or tablet from floating. A sinker may also be used for film-
coated tablets that stick to the vessel walls or to help position the
tablet or capsule under the paddle. The sinker should not alter the
dissolution characteristics of the dosage form.
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 Sinker types

 Sinker

 „a small loose piece of nonreactive material such as

 not more than a few turns of wire helix may be attached
 to dosage units that would otherwise float …“
 „…. other validated sinker devices may be used“

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Dissolution Apparatus III
(Flow-through cell apparatus)
 This is the third of three official dissolution
apparatuses described in the BP. It is defined in the
BP as follows:
 (a) "A reservoir for the dissolution medium."
 (b) A pump that forces the dissolution medium
upwards through the flow-through cell.
 (c) "A flow-through cell of transparent material
mounted vertically with a filter system preventing
escape of undissolved particles."
 (d) "A water bath that will maintain the dissolution
medium at 36.5° to 37.5° "
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Dissolution Apparatus III (Flow-
through cell apparatus) BP

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