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Presented by:
NAKAT ANUP RAMESH
1st semester,

Guided By: Dr.A.R.Madgulakar

Department Of Pharmaceutics,
÷


 
÷÷ 


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 ›


„ „ntroduction.
„ Zero Order Drug release.
„ First Order Drug release.
„ Weibull model
„ Higuchi model.
„ Hixon - Crowell Cube Root model.
„ Korsemeyer - Peppas equation.
„ Baker - lonsdale model
„ Hopfenberg model
„ Similarity factor.
„ Conclusion.
„ References.

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 —  

„ Definition-

„ „t 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.

„ Drug dissolution in an aqueous medium is an important

condition of systemic absorption.

„ Dissolution is the rate controlling step in the absorption of

drug with low solubility.
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„ Same amount of drug is released per unit time.

„ Drug dissolution from pharmaceutical dosage form that do

not disaggregate and release the drug slowly,
Can be given by following equation,

Q= Qo + Kot

Where,

Q =amount of drug released or dissolved.

Qo=initial amount of drug in solution.
Ko=zero order drug release constant .
˜
   
— 

„ Topical drug delivery system.

„ Transdermal drug delivery system.

„ „mplantable depot system.

„ Oral control release systems.

„ Oral osmotic tablets.

„ Matrix tablet with low solubility drug.

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„ As initial amount of drug

in solution is usually zero,
Zero order drug release
„ So equation becomes,
Q= Kot 

% cum ulative drug release

Hence to represent zero


 
  
 

order drug release, Plot of 

P
  is ¬
¬ ¬
¬ tim e¬
in hr ¬ 

plotted.


Æ To obtain good correlation between in vitro- in vivo
dissolution rate, „n vitro is always carried out under sink
condition.

• This can be achieved by:

Bathing the dissolving solid by fresh solvent from time to

time.
„ncreasing the volume of dissolution fluid.
Adding a Water miscible solvent such as alcohol to the
dissolution fluid.
By adding selected adsorbents to remove the dissolved
drug.

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— 
„ Sustained release dosage form.
„ Release rate depends on concentration of
drug.
„ Dissolution is said to be under nonsink condition.
„ Release rate equation for first order kinetics
can be given by,

-Kt
Qt=Q0e

Or

„n(Qt/Q0)=kt

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 É  




„ Hence to illustrate
relationship between
É



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drug release & time, plot
of P 

 
u
m n n
` 

    is ` 

` 

plotted. ` 
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`


`

`

`

 `    
 m n

`
„f we plot a graph between —

  


 

  

ë ë  ¬


  




¬ 

 ! ¬
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Fist order dissolution and ¬


 
 
    

Zero order dissolution

under sink and nonsink
condition are compared

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Æ This model can successfully applied to all kinds of dissolution
curve.
Æ This model express the accumulated fraction of the drug m,
in solution at time t,

’ Equation can be given by,

a- Scale parameter Ȃdefine as time scale of process.

Ti-location parameter-lag time before the onset o the
dissolution process.
b- shape parameter-characterize the curve
exponential (b=1)
sigmoid, s-shape (b>1)
parabolic with higher initial slope (b<1)

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„ Hence plot of, " m
  

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" 

  
 



  


¬
¬  ¬
  


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Disadvantage:
„t does not characterize the dissolution kinetic
properties of the drug.
Not any single parameter related with dissolution rate of
drug

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Æ Explained release of water soluble & poorly water soluble
drug from variety of matrixes including semisolid & solid.

Æ Higuchi equation is mainly followed, when release

of drug depend upon itǯs diffusion.

Æ Equation can be given by,

1/2
Mt / M0 = kt

Mt = amount of drug release in time t.

M0 =„nitial amount of drug release.
t= time required.

`˜
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 2i  i Eti 

„ Hence plot of P
ë
 #
 is plotted. 
2 
  

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¬

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Æ The geometric shape of the dosage form stays constant as
dissolution is occurring then the dissolution occurs in
plane that are parallel to the dosage form surface.
Æ The rate of dissolution is based on the cube root of the
weight of the particle.

’ Equation can be given by,

M01/3-M1/3= kt

Where,
M0=original mass of drug particles.
M =mass of particle undissolved.
t =time required.
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 2i  ±Cr w ll  r t lw

„ Hence plot of ë$


 is 2ixs  el ce t la

plotted. 




t f mass f
iss lve
     
    
    

    

ce
¬
¬
  
time i

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„ Model for understanding release behavior of
drug from hydrophilic matrix.

’ Equation can be given by,

Mt/Mϕ = Ktn

Mt = amount of drug release in time t.

Mϕ= amount of drug release in time ϕ.
k = constant related to structural & geometrical factors.
n = release exponent related to release mechanism used for
elucidation of drug release mechanism.
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„ Hence plot of 
ëP
 is plotted.
a

 
 
 
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%&% '  ()(*+ ,-./ 0(&
„ This plot explains the  0..*1.

 
.* %&% '  ()(*+ ,-.
"
#  /2,3& 0..*1.
diffusion mechanism by 

0(  0  4

which drug diffuses from     !

dosage form.     

„ n value indicates the

release mechanism.

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„ Developed from the Higuchi model.

„ Describes the Drug controlled released from Spherical

matrix.
’ Equation can be given by,

„ „f matrix is heterogeneous

„ Matrix porosity can be describe by:

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 iake
sale mel




„ Hence plot of  

left sie f eqati


#   is plotted.





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¬
   
tim e i 5

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„ The release of drug from surface-eroding devise with
several geometries was analysed by Hopfenberg.

„ He describes the drug released from slabs, spheres, infinite

cylinders showing heterogeneous erosion.

Mt-amount of drug dissolved in time t

Ko-erosion rate constant.
Co-initial conc. Of drug in matrix.
ao-initial radius of sphere or cylinder.
The value of n is 1,2,3 for slab , cylinder and and sphere
respectively.

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Æ Modified form of this model is developed in that the lag
time (l)is placed in the beginning of the drug release from
pharmaceutical dosage form.

Æ „n the rate limiting step of drug release the matrix erosion

is done. So this equation does not influence the matrix
erosion.

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„ Of all these above mentioned models, the kinetic model
that best fits the dissolution data was evaluated by
comparing the correlation coefficient ( r ) values obtained
in various models, the model that gave higher Ǯrǯ value is
considered as best fit model.

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„ tx%, Sampling time and Dissolution efficiency are the
parameter used to characterise drug release and gives
information of drug release.

„ tx%-time necessary to the release of a determined

percentage of drug.
„ Sampling time-amount of drug dissolved in that time.
„ Dissolution efficiency-

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„ Method that compare the drug release

1)Statistical method.
a) Single time point dissolution.
b) Multiple time point dissolution.

2)Model „ndependent method.

a) Ratio test procedure.
b) Pair wise procedure.

3)Model dependent method.

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1)Statistical method.

’ The method is based on in the analysis of variance can

be distinguished in one-way analysis of variance
(ANOVA) and multivariate analysis of variance
(MANOVA).

’ „t is the difference between the means of two drug

release data set in single time point dissolution or in
multiple time point dissolution.

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2) Model independent method.
a) Ratio test procedure-
„t is the relation between parameters obtain from release
assay of test of the reference formulation and the release
assay of test product at same time.

b) Pair wise procedure-

This includes:
1)Difference Factor.
2) Similarity factor.

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1)Difference factor.
„t is the percent error between two curves over
all time points, denoted by f1.

n-sampling number.
Rj-% dissolved of the reference product.
Tj-% dissolved of the test product.

„ The percent error is zero when test and reference profile are
identical.
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2)Similarity factor-
„ „t is logarithmic transformation of the sum- squared error
difference between the test and reference product over all
time points.

„ „t is used to denote similarity between two profile, denoted

by f2.
„ „t is fits results between 0-100

’ This method is more adequate to dissolution profile

comparisons when more than 3 or 4 dissolution time
points are available.
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’ FDA has set a standard of f1 value between 0 to 15 & f2 value
between 50 to 100 shows similarity of the dissolution
profile.

’ To compare dissolution treatment effect the 12 individual

dosage units should take.

’ Model independent method are very easy to apply.

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 ›



• Hence this conclusion can be drawn that the in

vitro drug release kinetics is necessary step to
be done to study the drug release patterns
from the dosage form.

• The graphs obtained from kinetic data states

the efficiency of drug release from the dosage form.

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