THEORY OF DRUG

DISSOLUTION
 DEFINITION
Dissolution is a process of separation solute molecule from the
solid solute and dispersion of the molecule into the solvent to which the
solute has been added

ie mass transfer from solid surface to liquid phase

Dissolution of solid in a liquid may be considered to be composed of two
consecutive stages,

1. Liberation of solute molecule from the solid surface to

stagnant diffuse layer adjacent to solid surface and

2. The transfer of these molecules from the boundary layer in

to the bulk of the liquid under the influence of diffusion.
The overall rate of mass transfer is decided by the step which is
slower if the rate of both the step are comparable the overall
mass transfer is influenced by both the steps

The rate of dissolution of a solid in a liquid is quantitatively given

by the Noyes Whitney equation
 SEVERAL THEORIES TO EXPLAIN DRUG
DISSOLUTION HAVE BEEN PROPOSED
Some of the important once are

Diffusion layer model or Film theory

Danckwerts model or Penetration or

surface renewal theory

Interfacial barrier model or double

barrier or limited solvation theory
DIFFUSION LAYER MODEL OR FILM
THEORY

Simplest and most common theory for dissolution

Here the process of dissolution of solid particle in a liquid in the

absence of reactive or chemical forces

this explained in the basis two steps of process

This process consist of two
consecutive steps:

Solution of solid to form a thin film or layer at

solid liquid interface called as stagnant film or
diffusion layer which is saturated with drug this
step is usually rapid

Diffusion of soluble solute from stagnant layer

to bulk of solution this step is slower so it is the
rate determining step in drug dissolution
 Noyes and Whitney Equation
It explain rate of dissolution
based on Ficks IInd law

dc
= K(Cs - Cb)
dt
dc
= dissolution rate of drug
dt
where

K = Dissolution rate constant

Cs = Concentration of drug in stagnant layer
Cb = Concentration of drug in
bulk of solution at time t
Burner in corperated Ficks first law of diffusion and modified the equation no.
(1)

dc
=DAKw/o (Cs Cb)
dt

Where
dC
H = thickness of
dt = dissolution rate of drug stagnant layer
D = Diffusion coefficient of drug
A = Surface area of dissolving solid
Kw/o = water oil partition coeffient of drug
V = Volume of dissolution medium
INFLUENCE OF VARIOUS PARAMETERS
ON
DISSOLUTION RATE OF DRUG
Parameters Symbol Influence on drug
dissolution
Diffusion D Greater the value faster the
coefficient of dissolution
drug
Surface area of A Greater the surface area
solid drug faster dissolution
Water oil Kw/o Higher value more
partition hydrophilicity faster
coefficient dissolution
Thickness of H More the thickness less
stagnant layer dissolution
DANKWERT MODEL
(SURFACE RENEWAL THEORY)

Don't approve existence of stagnant layer and suggest turbulence in the

dissolution medium exist at Solid/Liquid interface.

He suggest that the agitated fluid consisting of macroscopic mass of eddies or

packets reach Solid/Liquid interface in a random fashion due to eddy currents
solute is absorbed by diffusion and carry into bulk of solution
Such solutes containing packets are continuously replaced with new packets of
fresh solvent, so drug concentration at Solid/Liquid interface never reaches Cs
and lower limiting value Ci.

Since solvent packets are exposed to new solid surface each time. This theory
is called surface renewal theory
 dc dm
V = = A (Cs-Cb) D
dt dt

rate of surface removal

m mass of solid dissolved
Interfacial barrier model

The Diffusion layer model Danckwerts

model
is based on two assumption

1. The rate determining step that controls the dissolution in the

mass transport

2. Solid dissolution equilibrium is achieved at solid/liquid interface

According to interfacial barrier model:

an intermediate can exist at interface as a result of solvation mechanism and

it is a function of solubility rather than diffusion

When considering dissolution of crystals each face of crystal will have a

different interfacial barriers such concepts given by following equation

G = Ki (Cs-Cb)

G dissolution rate per

unit area
Ki Effective interfacial
transport constant
Equation represents first order dissolution rate process

The in vivo dissolution is always rapid than in vitro dissolution,

because the movement of drug dissolves into systemic circulation
as a result Cb = 0 dissolution is at its maximum

Thus under in vivo condition there is no concentration building up in the bulk

solution hence no retarding effect on dissolution rate of drug ie. Cs>>Cb, Sink
condition are maintained
Under sink condition if the volume and surface area of solid are
kept constant then equation became

=K

dc
Now it follows zero order kinetics
dt
Since condition can be achieved by:-
Bathening dissolving solid in fresh
solvent from time to time

Increasing the volume of distribution of

fluid

Addition of water miscible solvent

Eg: alcohol to dissolution fluid

By adding selected adsorbents to

remove dissolved drug
 FIRST ORDER,
NON-SINK CONDITION
CONCENTRATION OF

ZERO ORDER, SINK CONDITION

DISSOLVED DRUG

Time
WHY DO WE STUDY DISSOLUTION?

Drug in
Disintegration Dissolution Absorption the
blood
and the
body

21
DISSOLUTION AND DRUG RELEASE TESTS
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 in an aqueous medium under
specified conditions

The dissolution test is an important quality control procedure for

the drug product and is often linked to product performance in
vivo.

In-vitro drug dissolution studies are most often used for monitoring
drug product stability and manufacturing process
22
CONDITIONS THAT MAY AFFECT DRUG DISSOLUTION AND
RELEASE: DRUG AND FORMULATION RELATED

Drug substance
Particle size
Polymorph
Surface area
Chemical stability in dissolution media
Formulation of drug product
Excipients (lubricants, suspending agents, etc)

23
CONDITIONS THAT MAY AFFECT DRUG DISSOLUTION AND RELEASE:
METHODOLOGY RELATED
Medium
Volume
pH
Molarity
Co-solvents, added enzymes/surfactants
Temperature of medium
Apparatus
Hydrodynamics
Agitation rate
Shape of dissolution vessel
Placement of tablet in vessel
Sinkers (for floating products and products that
stick to side of vessel) 24
 DISSOLUTION APPARATUS
Apparatusa Name Drug Product

Apparatus 1 Rotating basket Tablets

Apparatus 2 Paddle Tablets, capsules, modified drug products, suspensions
Apparatus 3 Reciprocating cylinder Extended-release drug products
Apparatus 4 Flow cell Drug products containing low-water-soluble drugs
Apparatus 5 Paddle over disk Transdermal drug products
Apparatus 6 Cylinder Transdermal drug products
Apparatus 7 Reciprocating disk Transdermal drug products
Rotating bottle (Non-USP-NF) Extended-release drug products (beads)
Diffusion cell (Franz) (Non-USP-NF) Ointments, creams, transdermal drug products

aApparatus
17 refer to compendial dissolution apparatus in USP-NF (United States
Pharmacopeia) 25
ROTATING BASKET (APPARATUS 1)

26
ROTATING BASKET (APPARATUS 1)
In case of none-disintegrating dosage forms this apparatus is superior
to apparatus 2 since it constraints the dosage form in a steady state
fluid flow
It is inferior for testing dosage forms which contains gums due to
clogging of screen matrix

27
ROTATING BASKET (APPARATUS 1)
In the case of floating dosage forms this method performs well, but
care should be taken that excepients do not clog the basket mesh

28
ROTATING PADDLE (APPARATUS 2)

29
ROTATING PADDLE (APPARATUS 2)
This apparatus is identical to apparatus 1 except that the paddle is
substituted for the rotating basket

Frequently used for both disintegrating and non-disintegrating dosage

forms

30
RECIPROCATING CYLINDER (APPARATUS 3)

31
RECIPROCATING CYLINDER (APPARATUS 3)

One advantage of the reciprocating cylinder is that the

gastrointestinal tract conditions can be easily simulated, as it is easy to
make time dependent pH changes

This apparatus is most suitable for nondisintegrating (extended

release) or delayed release (enteric coated) dosage forms

32
FLOW CELL (APPARATUS 4)

33
FLOW CELL (APPARATUS 4)
The advantage of flow through cell apparatus is the ability to test
drugs of very low aqueous solubility and the ability to change the pH
conveniently during the test

34
PADDLE OVER DISK (APPARATUS 5)

35
CYLINDER (APPARATUS 6)
The cylinder method
(Apparatus 6) for testing
transdermal preparation is
modified from the basket
method (Apparatus 1). In place
of the basket, a stainless steel
cylinder is used to hold the
sample.

36
RECIPROCATING DISK METHOD (APPARATUS 7)

In the reciprocating disk method

for testing transdermal
products, a motor drive
assembly (Apparatus 7) is used
to reciprocate the system
vertically, and the samples are
placed on disk-shaped holders
using cuprophan supports

37
INTRODUCTION
Dissolution:

The transfer of molecules or ions from a solid state into solution is

known as dissolution.

Dissolution and then diffusion is a Pre-requisite for the drug

absorption.

Physicochemically, Dissolution is the process by which a solid

substance enters the solvent phase to yield a solution.

Dissolution (release of the drug from the dosage form) is of primary

importance for all conventionally constructed, solid oral dosage forms in
general, and for modified-release dosage forms in particular, and can be
the rate limiting step for the absorption of drugs administered orally.
 For the dissolution of solids, the process of dissolution can be
explained as the breakdown of the crystal lattice into individual ions,
atoms or molecules and their transport into the solvent.

For liquids and gases, the molecules must be compatible with those of
the solvent for a solution to form.

The process of dissolution may therefore be considered to involve the

relocation of a solute molecule from an environment where it is
surrounded by other identical molecules, with which it forms
intermolecular attractions, into a cavity in a liquid, where it is surrounded
by non-identical molecules, with which it may interact to different
degrees.
Dissolution Rate:

Dissolution rate may be defined as amount of drug substance that goes

in the solution per unit time under standard conditions of liquid/solid
interface, temperature and solvent composition.

The rate of dissolution quantifies the speed of the dissolution process.

The outcome of the process of dissolution (the amount dissolved at

equilibrium, i.e., the solubility) is governed by the thermo-
dynamic energies involved, such as the heat of solution and entropy
of solution.

AH is positive the dissolution process is usually an endothermic one,

i.e. heat is normally absorbed when dissolution occurs
Intrinsic Dissolution Rate:

Because the rate of dissolution is dependent on so many factors, it is

advantageous to have a measure of the rate of dissolution which is
independent of rate of agitation, area of solute available etc.

This is known as the intrinsic dissolution rate(IDR), which is the rate

of mass transfer per area of dissolving surface and typically has the units
of mg cm-2 min-1. IDR should be independent of boundary layer
thickness and volume of solvent.

Thus IDR measures the intrinsic properties of the drug only as a

function of the dissolution medium, e.g. its pH, ionic strength, counter
ions etc.
IMPORTANCE OF DISSOLUTION
STUDY
 Dissolution tests become especially important if dissolution is the rate-
limiting step in drug absorption, e.g., in rapidly disintegrating tablets or
capsules.

From a Quality Control perspective, dissolution testing is mainly used

to confirm product quality and batch-to-batch consistency and to identify
good and bad formulations.

Dissolution tests are used to confirm compliance with compendial

(summary of a larger work) specifications and are therefore needed as
part of a marketing authorization.( e.g. Disprin fast dissolving tablet).

Dissolution testing is widely used in the pharmaceutical industry for

optimization of formulation and quality control.
 Additionally they are used during product development and stability
testing as part of the development specification for the product. Critically
from an R&D perspective, there is the potential to correlate in vitro
dissolution data with in vivo bioavailability, which would greatly
facilitate product development.

Most sensitive and reliable predictors of in-vivo availability.

Such models can be used to screen potential drug and their associated
formulations for dissolution and absorption characteristics.

Dissolution study also identify potential bioavailability problems.

OBJECTIVES OF DISSOLUTION
TESTING
 Dissolution testing as a QC test, to guide formulation development, to
use as a manufacturing/process control tool.

Dissolution also act as a quality control tool for the uniformity and
reproducibility of the batches.

Increasingly, in vitro dissolution testing and profile comparison are

relied on to assure product quality and performance and to provide a
biowaiver.( Biowaiver is the official approval for exemption from
conducting a bioequinalence study in the context of an application for
marketing authorization).

Dissolution studies are used to substitute bioabsorption (in-vivo)

where in-vivo in-vitro corelation are observed.
 Itis research tool to optimize the parameters and ingredients in new
formulations.
It is also used to assess drug product quality with respect to stability
and shelf life.
To develop a composition and process for Phase I clinical studies
which are consistent with the intended market composition (qualitative
and quantitative).
To develop a highly discriminating dissolution test; not as a quality
control tool but as an aid to optimization of a formulation.
To develop a dosage form with a consistently high performance
throughout its life.
To develop a dissolution test to serve as a quality control tool.
 FACTORS AFFECTING DISSOLUTION
RATE
1. Physicochemical Properties of Drug
2. Drug Product Formulation Factors
3. Processing Factors
4. Factors Relating Dissolution Apparatus
5. Factors Relating Dissolution Test Parameters
6. Miscellaneous factor
A. PHYSICOCHEMICAL PROPERTIES OF
DRUG:
1. Solid-Phase Characteristics:
Amorphicity and crystallinity,
have been shown to have a
significant effect or the dissolution
rate.
Amorphous form of a drug usually
exhibits greater solubility and
higher dissolution rate as
compared to the crystalline form.
Where in Dissolution rate of
amorphous erythromycin estolate
is markedly lower than the
crystalline form of erythromycin
estolate.
2. Solubility of Drug:
Play Major Role In Dissolution Testing By Controlling Dissolution.
Aqueous Solubility of Drug is major factor that determines
Dissolution.
Minimum 1% aqueous solubility is required to avoid solubility
dependent absorption problems.

3. Salt Formation:
Most comman approach
Sodium salts dissolve faster than their corresponding insoluble acids.
Eg.Sodium and potassium salts of Peniciilin G, sulfa drugs,
phenytoin, barbiturates etc.
4. Particle Size:
Dissolution rate is directly proportional to surface area.
Micronization increase effective surface area, so increase dissolution
rate.
5. Co-Precipitation
Dissolution rate of sulfathiazole could be significantly increased
by co-precipitating the drug with povidone.

6. Polymorphism
Polymorphism and state of hydration, salvation, and complexation,
markedly influence dissolution characteristic of drug by change in
solubility characteristic of drug .Ex- Tolbutamide and Chloramphenicol.
B. DRUG PRODUCT FORMULATION
FACTORS:
1. DILUENTS:
Dissolution rate of salicylic acid tablet by
dry double compression process shows
three times increase in dissolution rate
when the starch content increase from the 5
20 %.
Starch particles form a layer on the outer
surface of hydrophobic drug particles
resulting in imparting hydrophilic
character granules & thus increase in
effective surface area & rate of dissolution.
Dissolution rate is also affected by excipient dilution (drug/excipient
ratio).E.g. in quinazoline comp. dissolution rate increases as the
excipient /drug ratio increases from 3:1 to 7:1 to 11:1.
2. DISINTEGRANTS:
Added before & after the granulation affects the dissolution rate.
e.g. Na CMC, MCC, Starch, etc.

3. BINDERS AND GRANULATING AGENTS:

Hydrophilic binder show better dissolution profile with hydrophobic
drug like Phenacetin by implanting hydrophilic properties to granule
surface.
Large amt. of binder increase hardness & decrease disintegration
/dissolution rate of tablet.
Phenobarbital tablet granulated with gelatin solution provide a faster
dissolution rate in human gastric juice than those prepared using Na
carboxymethyl cellulose or polyethylene glycol 6000 as binder.
4. LUBRICANTS:
Nature, quality, quantity of lubricant can affect dissolution rate.
Effect of Magnesium Stearate on dissolution of salicylic acid tablet.

It should be added in small amount (1% or less) and should be tumbled

or mixed gently for only very short time. Prolonged mixing will increase
the dissolution time.
5. SURFACTANTS:
They enhance the dissolution rate of poorly soluble drug. This is due to
lowering of interfacial tension, increasing effective surface area, which
in turn results in faster dissolution rate.
E.g Non-ionic surfactant Polysorbate 80 increase dissolution rate of
phenacetin granules.

6. COATING POLYMERS:
Tablets with MC coating were found to exhibit lower dissolution
profiles than those coated with HPMC at 37C.
C. PROCESSING FACTORS:
1. METHOD OF GRANULATION:
Wet granulation to improve dissolution rate of poorly soluble drug by
imparting hydrophillic properties to the surface of the granules.
Wet granulation is superior to a dry .
A newer technology called as APOC Agglomerative Phase of
Comminution produce mechanically stronger tablets with higher
dissolution rates than wet granulation.
Increased internal surface area of granules produced by APOC
method.
2. COMPRESSION FORCE:
The compression process influence density, porosity, hardness,
disintegration time & dissolution of tablet.
i. First condition, higher compression
force increase the density & hardness of
tablet, decrease porosity & hence
penetrability of solvent into the tablet so
decrease dissolution rate of tablet.

ii. Second condition, higher

compression force cause
deformation, crushing or fracture of
drug particles into smaller ones or
convert spherical granules into disc
shaped particles with a large
increase in the effective surface area
so increase in dissolution rate.
In short dissolution decrease at lower pressure (better bonding), then
increase at higher pressure (crushing effect) and decrease again with
further increase in pressure bcz of extra rebonding and formation of
denser tablets with poorer dissolution characteristics.

3. DRUG EXCIPIENT INTERACTION

These interactions occur during any unit operation such as mixing,
milling, blending, drying, and/or granulating result change in
dissolution.
The dissolution of prednisolone found to depend on the length of
mixing time with Mg-stearate
4. STORAGE CONDITIONS:

Dissolution rate of Hydrochlorothiazide tablets granulated with acacia

exhibited decrease in dissolution rate during 1 yr of aging at R.T.

Tablets with starch gave no change in dissolution rate either at R.T. or at

elevated temperature.
D. FACTORS RELATING DISSOLUTION
APPARATUS:
1. AGITATION
Depend on -
Type of agitation used
The degree of laminar and turbulent flow in system
Speed of agitation
The shape and design of stirrer
In general relatively low agitation should be applied
a) BASKET METHOD- 100 rpm
b) PADDLE METHOD- 50-75 rpm
2. FLOW PATTERN DISTURBANCES
The geometry and alignment of the stirring device, external vibration,
and rotational speed are some of the factors that can influence flow
patterns.
The influence on flow patterns of the vertical distance of the basket or
paddle from the lowest point of the bottom of the round-bottomed flask
should also be considered. The official compendium specifies this
distance to be 2.5 cm (2 mm).
3. SAMPLING PROBE POSITION & FILTER
Sampling probe can affect the hydrodynamic of the system & so that
change in dissolution rate.
For position of sampling, USP / NF states that sample should be
removed at approximately half the distance from the basket or paddle
to the dissolution medium and not closer than 1 cm to the side of the
flask.
E. FACTORS RELATED DISSOLUTION TEST
PARAMETERS:
1. TEMPERATURE
Temperature affects the speed at which particles move. Particles move
more rapidly at higher temperatures, as heat is transferred by the
movement of the particles.
Drug solubility is temperature dependent, therefore careful temperature
control during dissolution process is extremely important.

2. DISSOLUTION MEDIUM
The constituents, nature, and overall characteristics of the dissolution
medium have a significant bearing on the dissolution performance of a
drug
Factors such as dissolved gases, media pH, and volume & viscosity of
the medium have been shown to be significantly influential on
dissolution rate.
F. MISCELLANEOUS FACTORS:

1. HUMIDITY
Humidity is usually associated with storage effects.

Moisture has been shown to influence the dissolution of many drugs

from solid dosage forms.

Hanson and Hanson found that three of the four formulations of

prednisone tablets showed drastic decreases in dissolution rate when the
tablets were exposed to high humidity.
2. ABSORPTION
The relative density of the tablets was found to decrease, resulting in
increased disintegration time with increase in water sorption-rate
constants.
3. DETECTION ERRORS

Analytical methods be checked carefully for each dissolution system.

Extreme care must also be exercised when laboratory methods are

introduced into quality control to ensure that no part of the equipment
interferes with sensitive determinations.
DISSOLUTION EQUIPMENTS
IDEAL DESIGN OF DISSOLUTION APPARATUS

The fabrication, dimensions and, positioning of all components must be

precisely specified and reproducible.
The apparatus must be simply designed, easy to operate, and useable
under a variety of conditions.
Uniformity of flow is essential
The apparatus must be sensitive enough to formulation differences but
still yield repeatable results under identical conditions.
Nearly perfect sink conditions should be maintained.
The apparatus should provide an easy means of introducing the dosage
form into the dissolution medium.
The apparatus should provide minimum mechanical abrasion to the
dosage form.
Evaporation of the solvent medium must be eliminated
and the medium must be maintained at a fixed temperature within a
specified narrow range. Most apparatus are thermostatically controlled at
around 37oC.
Samples should be easily withdrawn for automatic or manual analysis
without interrupting the flow characteristics of the liquid.
The apparatus should be capable of allowing the evaluation of
disintegrating, non-disintegrating, dense or floating tablets, or capsules
and finely powdered drugs.
The apparatus should allow good interlaboratory agreement.
OFFICIAL DOSSOLUTION MONOGRAPHS

I.P. USP B.P. E.P.

Type I paddle basket apparatus basket apparatus paddle apparatus

apparatus
Type II basket paddle apparatus paddle apparatus basket apparatus
apparatus
Type III Reciprocating flow through cell flow through cell
cylinder apparatus apparatus
Type IV flow through cell
apparatus
Type V Paddle over disk
Type VI cylinder

Type VII reciprocating holder

According to USP 30 dissolution apparatus used are:

USPAPP DESCRIPTION ROT.SPEED DOSAGE FORM

.

I BASKET 50-120 rpm IR, DR, ER

II PADDLE 25-50 rpm IR, DR, ER

III RECIPROCATING 6-35 rpm IR, ER

CYLINDER
IV FLOW-THROUGH CELL N/A ER, POORLY SOLUBLE
API
V PADDLE OVER 25-50 rpm TRANSDERMAL
DISK

VI CYLINDER N/A TRANSDERMAL

VII RECIPROCATING 30 rpm ER

HOLDER
USP Apparatus I- Basket Apparatus
Useful for Drug Product:
Capsules, Beads, Delayed release /
Enteric Coated dosage forms,
Floating dosage forms

Standard volume: 900/1000 ml

1, 2, 4 liter vessels

Agitation
Rotating stirrer
Usual speed: 50 to 100 rpm
Advantages:
1) more than 200 monographs.
2) Full pH change during the test
3) Can be easily automated which is important for routine investigation.

Disadvantages:
1)Disintegration-dissolution interaction
2)Hydrodynamic Dead jone under the basket.
3)Degassing is particularly important
4)Limited volume-sink condition for poorly soluble drugs.
USP Apparatus-II - Paddle Apparatus.

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 no reactive
material such as not more than a few
turns of wire helix may be attached
to dosage units that would otherwise
float.
Useful
for :
Tablets
Capsules
Standard volume: 900/1000 ml
Agitation
Rotating stirrer
Usual speed: 25 to 75 rpm
Advantages:
Easy to use
Robust
Can be easily adapted to apparatus 5
long experience
pH change possible
Can be easily automated which is important for routine investigations.
Disadvantages:
media change is often difficult
Hydrodynamics are complex, they vary with site of the dosage form in
the vessel (sticking, floating) and therefore may significantly affect drug
dissolution.
USP Apparatus III Reciprocating cylinder
The assembly consists of a set of cylindrical, flat-bottomed glass
vessels; a set of glass reciprocating cylinders; stainless steel fittings (type
316 or equivalent) and screens that are made of suitable nonsorbing and
nonreactive material (polypropelene) and that are designed to fit the tops
and bottoms of the reciprocating cylinders; and a motor and drive
assembly to reciprocate the cylinders vertically inside the vessels.

The vessels are partially immersed in a suitable water bath of any

convenient size that permits holding the temperature at 37 0.5oC
during the test.

Useful for: Tablets, Beads, controlled release formulations

Standard volume: 200-250 ml/station

Advantages:
1) Easy to change the pH-profiles
2) Hydrodynamics can be directly influenced by varying the dip rate.

Disadvantages:
1) small volume (max. 250 ml)
2) Little experience
3) Limited data
USP Apparatus IV Flow through cell
The assembly consists of a reservoir and a pump for the Dissolution
Medium; a flow-through cell; a water bath that maintains the Dissolution
Medium at 37 0.5oC.
The cell size is specified in the individual monograph.
The pump forces the Dissolution Medium upwards through the flow-
through cell.
Place the glass beads into the cell specified in the monograph.
Place 1 dosage unit on top of the beads or, if specified in the
monograph, 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 0.5oC
through the bottom of the cell to obtain the flow rate specified in the
individual monograph.
Collect the elute by fractions at each of the times stated.
Useful for:
Low solubility drugs
Micro particulates
Implants & Suppositories
Controlled release formulations
Variations: (A) Open system & (B) Closed system

Advantages:
Easy to change media pH
PH-profile possible
Sink conditions
Disadvantages:
De-aeration necessary
High volumes of media
Labor intensive
USP Apparatus V Paddle over disk
Use the paddle and vessel assembly from Apparatus 2 with the addition
of a stainless steel disk assembly designed for holding the transdermal
system at the bottom of the vessel.
The temperature is maintained at 32C 0.5C
The disk assembly holds the system flat and is positioned such that the
release surface is parallel with the bottom of the paddle blade
Borosilicate Glass
17 mesh is standard (others available)
Accommodates patches of up to 90mm
USP Apparatus VI cylinder
Use the vessel assembly from Apparatus 1 except to replace the basket
and shaft with a stainless steel cylinder stirring element and to maintain
the temperature at 32 0.5oC during the test.

The dosage unit is placed on the cylinder at the beginning of each test,
to the exterior of the cylinder such that the long axis of the system fits
around the circumference of the cylinder & removes trapped air bubbles.

Place the cylinder in the apparatus, and immediately rotate at the rate
specified in the individual monograph.
USP Apparatus VII reciprocating holder
The assembly consists of a set of volumetrically calibrated solution
containers made of glass or other suitable inert material a motor and
drive assembly to reciprocate the system vertically and a set of suitable
sample holders.
The solution containers are partially immersed in a suitable water bath
of any convenient size that permits maintaining the temperature, inside
the containers at 32 0.5 For Coated tablet drug delivery system attach
each system to be tested to a suitable Sample holder (e.g., by gluing
system edge with 2-cyano acrylate glue onto the end of a plastic rod or
by placing the system into a small nylon net bag at the end of a plastic
rod or within a metal coil attached to a metal rod).
For Transdermal drug delivery system attach the system to a suitable
sized sample holder with a suitable O-ring such that the back of the
system is adjacent to and centered on the bottom of the disk-shaped
sample holder or centered around the circumference of the cylindrical-
shaped sample holder. Trim the excess substrate with a sharp blade.
Reciprocate at a frequency of about 30 cycles per minute with amplitude
of about 2 cm, or as specified in the individual monograph, for the
specified time in the medium specified for each time point.
REFERENCES:

1. Aulton M.E. Pharmaceutics The Science of Dosage Form Design,

2nd Ed.; Churchill Livingstone.
2. Hiemenz, P.C. Principles of Colloid and Surface Chemistry, 2nd Ed.;
Marcel Dekker, Inc.: New York, 1986
3. Pharmaceutical Dissolution Testing, Edited by Jennifer Dressman And
Johannes Kramer, Published in 2005 by Taylor & Francis Group, LLC
6000 Broken Soubd Parekway NW, Suite 300.
4. http://wiki.answers.com / http://en.wikipedia.org
5. www.who.int
6. http://www.pharmacopeia.cn
THANK YOU