dissolution models ,higuchi model,peppas model etc

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2. DISSOLUTION MODELS
Presented by: Miss.Supriya Wable.
M.Pharm,1st Year
Dept: Pharmaceutics
Dattakala College of Pharmacy
Date :14/11/2019
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3. CONTENT
 What is dissolution?
 Dissolution model
 Types of dissolution model
 Diffusion layer model
 dankwart’s model
 Interfacial barrier model
 Higuchi model
 koresmeyer’s peppas model
 Conclusion
 Reference
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4. What is Dissolution?
 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.”
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5. Dissolution model and it’s need
Dissolution profile: It is a graphical representation
[in term of concentration vs time ] of complete
release of A.P.I. from a dosage form in an
appropriate selected dissolution medium. i.e. in
short it is a measure of release of A.P.I. from
dosage form with respect to time.
 It’s Need
 To develop invitro- invivo correlation which can
help to reduce costs, speed up product
development.
 To stabilize final dissolution specification for
pharmacological dosage form.
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6. FACTOR AFFECTING
DISSOLUTION RATE .
1. Physicochemical Properties of Drug:
a. Drug Solubility
b. salt formation
c. solid state characteristic
d. particle size
e. co-precipitation
2. Drug product formulation factors:
a. diluents
b. Disintegrants
c. binder
d. surfactants
e. lubricants 11/14/2019 6

7. 3. Processing factors:
a. Method of granulation
b. Compression force
c. Storage condition
4. Factors relating dissolution apparatus and
test parameter:
a. agitation
b. Temperature
c. Dissolution medium, pH
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8. Types of Dissolution models
 Diffusion layer model
 Danckwert’s model
 Interfacial barrier model
 Higuchi model
 Korsmeyer- Peppas model
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9. 1.Diffusion layer model
 It is a simplest model where dissolution of crystal,
immersed in liquid takes place without involving reactive
or electrical forces.
 Consist of two consecutive steps:
1. Solution of the solid to form a thin film or layer at the
solid / liquid interface called as stagnant film or diffusion
layer which is saturated with the drug this step is usually
rapid .
2. Diffusion of the soluble solute from the stagnant layer to
the bulk of the solution this step is slower and is therefore
the rate determining step in the drug dissolution.
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11.  Using Fick’s law, Noyes- Whitney equation for
diffusion layer model is as follows,
dc/dt = DAKw/o(Cs-Cb)/vh
Where,
dc/dt = dissolution rate of the drug
D = diffusion coefficient of the drug
A = surface area of the dissolving solid
Kw/o = water/oil partition coefficient of the drug
V = volume of dissolution medium
h = thickness of the stagnant layer
(Cs-Cb) = concentration gradient of diffusion of drug
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12. 2.Dankwaet’s model
 This theory assumes that solid-solution equilibrium
is achieved at interface and mass transport is slow
step in dissolution process.
The model could be visualized as a very thin film having
a conc. Ci which is less than saturation, as it is constantly
being exposed to fresh surfaces of liquid having a conc.
much less than Ci
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13.  According to model, the agitated fluid consist of
mass of eddies or packets that are continuously
being exposed to new surfaces of solid and then
carried back to bulk of liquid.
 The Danckwert’s model can be expressed by
the following equation,
V.dc/dt=dm/dt=A(Cs-Cb)√(y.D)
where,
m = mass of solid dissolved
y = rate of surface renewal
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14. 3.Interfacial barrier model
 Interfacial barrier model considers drug dissolution
as crystal dissolution where in solids get hydrated
initially and is not instantaneous.
 In this model it is assumed that the reaction at
solid surface is not instantaneous
 therefore the rate of solubility of solid in liquid
film becomes the rate limiting than the diffusion of
dissolved molecules
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15.  When considering the dissolution of crystal will
have a different interfacial barrier given by the
following equation,
dm/dt=Ki ( Cs-C)
where,
Ki = effective interfacial transport constant
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16. 4.Higuchi model
 This is the first mathematical model that describes drug
release from a matrix system, proposed by Higuchi in 1961
.
 This model is based on different hypothesis that,
 Initial drug concentration in the matrix is much higher
than drug solubility,
 Drug diffusion takes place only in one dimension ,
 Drug particles are much smaller than thickness of system,
 swelling of matrix and dissolution are less or negligible,
 Drug diffusivity is constant,
 Perfect sink condition are always attained in the release
environment.
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17.  The study of dissolution from a planar system
having a homogeneous matrix can be obtained by
the equation:
A=[D(2C-Cs)Cs×]1/2
Where,
A = amount of drug released in time ‘t’ per unit area
D = diffusivity of drug molecule in the matrix
substance
C = initial drug concentration
Cs = drug solubility in the matrix media.
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18.  The following graph shows the drug release
through Higuchi Model,
Application : This relationship can be used to
describe the drug dissolution from several types
of modified release pharmaceutical dosage forms,
as in the case of some transdermal systems and
matrix tablets with water soluble drugs.
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19. 5.Korsemeyer – peppas model
 Korsemeyer (1983) derived a simple relationship
which described drug release from a polymeric system
equation.
 The Korsemeyer –Peppas empirical expression relates
the function of time for diffusion controlled
mechanism.
 It is given by the equation,
Mt / M∞ = Ktn
Where, Mt / M∞ is a fraction of drug released
t = time
k = release rate constant includes structural and
geometrical characteristic of the dosage form .
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20. n = release component which is indicative of the drug
release mechanism.
where, n is diffusion exponent
 if n = 1, the release is zero order
 if n= 0.5 the release is best described by Fickian
diffusion
Application: This equation has been used to the
linearization of release data from several
formulations of microcapsules or microspheres.
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21. 6.Baker- Lonsdale model
 This model was developed by Baker and Lonsdale (1974)
from the Higuchi model and described the drug release
from spherical matrices by using the equation:
f1= 3/2[1-(1-Ct/C∞)2/3] Ct/C∞ =
(3DmCms)/(ro2Co)X t
Where,
At = drug released amount at time
t A∞ = amount of drug released at an infinite time,
Dm = diffusion coefficient,
Cms = drug solubility in the matrix,
ro = radius of the spherical matrix
Co = initial concentration of drug in the matrix
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22.  To study the release kinetics, data obtained
from in vitro drug release studies were plotted as
[d (At / A∞)] / dt with respect to the root of time
inverse.
Application:
 This equation has been used to the linearization
of release data from several formulations of
microcapsules or microspheres.
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23. Conclusion
 The Quantitative interpretation of the values
obtained and dissolution assay is easier using
mathematical equation which describes the
release profile in function of some parameters
related with the pharmaceutical dosage form.
 The release model has the major appliance and
the best describing drug release phenomenon.
 The Higuchi model has the large application in
polymeric system, the zero order model
becomes ideal to describe coated dosage forms
or membrane controlled dosage form
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24. Reference
 Brahmankar, “A textbook of Bio pharmaceutics
and Pharmacokinetic”, 3 rd edition, page no.15-
48.
 Ramteke K H ,Dighe P.A , Kharat A R , Patil S
V; Mathematical models of drug dissolution : A
Review by Scholars Academic Journal of
Pharmacy ,page no 390.
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