Dissolution chapter and different mechansims

Guided By:-
Mr. Sanket Gandhi
Asst. Professor
Dept. of Pharmaceutics
Presented By:-
Chirag Lathiya
M.Pharm 1st Sem.
BHAGWAN MAHAVIR COLLEGE OF PHARMACY, SURAT.
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CONTENTS
 Definition
 Importance
 Intrinsic Dissolution Rate
 Dissolution media
 Apparatus
 Dissolution Acceptance criteria
 Conclusions
 References
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DEFINITION
 Dissolution is a process in which a solid substance
solubilizes in a given solvent i.e. mass transfer from the
solid surface to the liquid phase.
 Rate of dissolution is the amount of drug substance that
goes in solution per unit time under standardized
conditions of liquid/solid interface, temperature and
solvent composition.
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IMPORTANCE
 Results from in-vitro dissolution rate experiments can be
used to explain the observed differences in in-vivo
availability.
 Provides the means to evaluate critical parameters such as
adequate Bioavailability.
 Provides information necessary to formulator in
development of more efficacious and therapeutically
optimal dosage forms.
 Most sensitive & reliable predictors of in-vivo availability.
 It can ensure bioavailability of product between batches
that meet dissolution criteria.
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 Ensure quality of product.
 Ensure batch-to-batch quality equivalence both in-vitro
and in-vivo.
 Physicochemical properties of model can be understood
needed to mimic in-vivo environment.
 Serve as quality control procedures, once the form of drug
and its formulation have been finalized.
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INTRINSIC DISSOLUTION RATE (IDR)
 IDR of a pure substance is the rate at which it dissolves
from a constant surface area whilst the temperature,
agitation, pH, and ionic strength of the dissolution
medium are KEPT CONSTANT.
 Thus, for a drug substance, the IDR is independent of
formulation factors and measures the inherent solubility of
the drug in the dissolution medium.
 Thus, IDR determinations can be used to characterize bulk
drug substances and excipients and to test the chemical
equivalence of active pharmaceutical ingredients
synthesized by different processes. 6

• The IDR is a key indicator of the potential bioavailability
of a candidate drug
where an IDR > 1.0mg/min/cm2 suggests that drug
dissolution will not be the rate-limiting step to absorption
whilst an IDR < 0.1mg/min/cm2 suggests that drug
dissolution will be the rate limiting step to absorption. An
intermediate value suggests that drug dissolution may be
the rate-limiting step to absorption.
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INTRINSIC DISSOLUTION METHOD
8
Rotating
Disk Apparatus
Stationary Disk Apparatus
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DISSOLUTION MEDIUM
It is very important factor affecting dissolution
and is itself affected by number of factors such as:
Effect of pH
Volume
Deaeration
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EFFECT OF pH
 For Weak bases, Dissolution rate increase with
decrease in pH
 For Weak acids, Dissolution rate increases with
increase in pH
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VOLUME OF MEDIUM
500 to 1000 ml
900 ml is Generally Used
 Can be Raised to 2 to 4 lit.
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DEAERATION
 Air Bubbles can :
 Interfere with the Result
Can Cause Particles to Cling to the Apparatus and Vessel
Walls
 Deaeration can be done by :
Heating
Filtering
Vacuum
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DISSOLUTION MEDIUM EXAMPLE
Water Ampicillin caps., Butabarbital
sodium tabs.
Buffers Azithromycin caps.,
paracetamol tabs.
HCL solution Cemetidine tabs.
Simulated gastric fluid Astemizole tabs., piroxicam
caps.
Simulated intestinal fluid Valproic caps., Glipizide tabs.
Surfactant solution Clofibrate caps, danazol caps
Medium has a pH of 5.00 and an osmolality of about 635 mOsm/kg.
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CLASSIFICATION
There are basically three general categories of
dissolution apparatus :
 Closed compartment apparatus (Beaker methods)
 Open flow-through compartment system
 Dialysis concept
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1. CLOSED COMPARTMENT
APPARATUS (Beaker methods)
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Rotating Basket Apparatus (Apparatus 1)
Contain cylindrical glass vessel with hemispherical
bottom of 1 L capacity partially immersed in a water
bath.
A cylindrical basket made of #22 mesh is located
centrally in the vessel at a distance of 2 cm from the
bottom and rotated by a variable speed motor through a
shaft.
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All metal parts like basket and shaft are made of stainless
steel 316.
The latter should be made of materials that do not sorb or
react with the sample tested. The contents are held at 37 C
+ 0.5 C.
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A 2.5 mm thick gold coating on the basket may be used
for acidic media.
The shaft rotation speed should be maintained within
4% of rate specified in monograph.
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Rotating Paddle Apparatus (Apparatus 2)
Here, basket is replaced with a paddle which acts as a
stirrer.
It consisted of a 400 ml beaker and a three-blade. centrally
placed polyethylene stirrer (5 cm diameter) rotated at 59
rpm in 250 ml of dissolution fluid (0.1N HCl).
Tablet was placed down the side of the beaker & samples
were removed periodically.
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The metallic blade and shaft may be coated with a suitable
inert coating to prevent corrosion.
A small, loose, wire helix may be attached to the dosage form
to prevent them from float.
The dosage form is allowed to sink to the bottom of the flask
before rotation of the blade commences.
In the case of hard-gelatin capsules & other floating dosage
forms, a ‘‘sinker’’ is required to weight the sample down until
it disintegrates and releases its contents at the bottom of the
vessel.
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The Reciprocating Cylinder Method
(Apparatus 3)
The disks are not used.
 It has been designed to allow the tubes to be dipped
sequentially in up to six different media vessels, using
programs that vary the speed and duration of
immersion.
The dosage unit is placed in reciprocating cylinder &
cylinder is allowed to move upward & downward
direction constantly.
21

It allows automated testing for up to six days and the
manufacturers advocate its use in the test in of extended-
release dosage forms.
This method is less suitable for precise dissolution
testing due to the amount of agitation and vibration
involved.
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Paddle over Disk method (Apparatus 5)
Modification of Apparatus 2.
Here, stainless steel disk designed for holding
transdermal system at the bottom of the vessel.
The disk/device should not sorb, react with, or
interfere with the specimen being tested.
The disk holds the system flat and is positioned such
that the release surface is parallel with the bottom of
the paddle blade.
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Cylinder method (Apparatus 6)
Same as apparatus 1, except to replace the basket and
shaft with a S.S. cylinder stirring element.
Temperature - 32 ± 0.5°
The dosage unit is placed on the cylinder.
Distance between the inside bottom of the vessel and
cylinder is maintained at 25 ± 2 mm.
The sample is again usually a transdermal delivery
system attached to the outside of the cylinder.
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Reciprocating Holder method (Apparatus 7)
The assembly consists of a set of calibrated solution
containers, a motor and drive assembly to reciprocate the
system vertically.
Various type of sample holder are used.
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Advantages of the Beaker Methods
The basket method is the most widely used procedure
which confines the solid dosage form to a limited area
which is essential for better reproducibility.
It is advantageous for capsules as they tend to float at the
surface thus minimizing the area exposed to the
dissolution fluid.
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Limitation of the Beaker Methods
Clogging of the basket screen by gummy particles.
Tendency of the light particles to float.
Sensitivity of the apparatus to variables such as
vibration, eccentricity, etc.
Rapid corrosion of the SS mesh in presence of HCl.
Sensitivity of the apparatus to any slight changes in the
paddle orientation.
Non-reproducible position of the tablets at the bottom of
the flask.
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2. OPEN FLOW-THROUGH
COMPARTMENT SYSTEM
The dosage form is contained in a small vertical glass
column with built in filter through which a continuous
flow of the dissolution medium is circulated upward at
a specific rate from an outside reservoir using a
peristaltic or centrifugal pump.
Dissolution fluid is collected in a separate reservoir.
E.g. lipid filled soft Gelatin capsule
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Schematic diagram of a flow-through dissolution cell
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Advantages
 There is no physical abrasion of solids.
 Easy to maintaining of sink conditions during dissolution
which is often required for drugs having limited aqueous
solubility.
 selection of laminar or turbulent solvent flow conditions .
Feasibility of using large volume of dissolution fluid.
 simple manipulation of medium pH to match
physiological conditions.
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Disadvantages
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.
Temperature control is also much more difficult to achieve
in column type flow through system than in the
conventional stirred vessel type.
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3. DIALYSIS SYSTEM
Here, dialysis membrane used as a selective barrier
between fresh solvent compartment and the cell
compartment containing dosage form.
It can be used in case of very poorly soluble rugs and
dosage form (such as ointments, creams and suspensions)
for which maintenance of sink conditions would otherwise
require large volume of dissolution fluid.
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APPLICATIONS
APPARATUS DRUGS FORMULATED TESED
 Rotating Basket (Appa. 1)
 Rotating paddle (Appa. 2)
 Reciprocating cylinder
(Appa. 3)
 Flow-through cell (Appa. 4)
 Paddle over disc (Appa. 5) &
Cylinder(Appa. 6)
 Reciprocating disc (Appa.
7)
 Conventional tablets, Chewable tablets,
Controlled-release formulations
 Tablets, Orally disintegrating tablets,
Chewable tablets, Capsules, controlled-
release formulations, suspensions
 Controlled-release formulation, Chewable
tablets
 Formulations containing poorly soluble
drugs, Powders & Granules,
Microparticles, Implants
 Transdermal formulations
 Controlled-release formulation &
Transdermal formulations 36
26 september 2012

Dissolution Acceptance Criteria
 Dissolution Acceptance Criteria are based on Q values.
The value of Q is defined as percentage of drug
content dissolved in a given time period.
 This value is generally specified in USP monograph of a
given drug product.
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STAGE NUMBER OF DOSAGE
. UNITS TESTED
ACCEPTANCE CRITERIA
 S1 6
 S2 6
 S3 12
 No dosage unit is less than Q+5%
 Average of the twelve dosage units
(S1+S2) > Q% and dosage unit is less
than Q-15%
 Average of the 24 dosage units
(S1+S2+S3) > Q% and not more
than two dosage units are less than Q-
15% and no dosage unit is less than
Q-25%
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CONCLUSIONS
 The increasing importance of dissolution testing in the
development and routine commercial production of
pharmaceuticals has become acknowledged within the
industrial, academic, and regulatory communities.
 Improvements in dissolution testing instrumentation and
an awareness of the importance of correlating in vitro data
with in vivo performance have offered the possibility of
more rapidly developing safer and more efficacious drugs.
 This has, in turn, led to an increase in interest amongst
equipment manufacturers to produce more sophisticated
instrumentation capable of routine, automated operation.
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REFERENCES
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 Biopharmaceutics & Pharmacokinetics by
D.M.Brahmankar, 20-29.
 Encyclopedia Of Pharmaceutical Technology ,Third
Edition, Volume 1 by James Swarbrick, 908-921
 http://pharmaquest.weebly.com/uploads/9/9/4/2/9942916/
equip_of_dissolution.pdf

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