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Contents
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y y y y y y y y y y y
Introduction. 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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Dissolution
y Definitiony It 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.
y Drug dissolution in an aqueous medium is an important
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 .
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y So equation becomes,
Q= Kot Hence to represent zero order drug release, Plot of % Cumulative drug Release Vs time is plotted.
6 % cum ulative drug release 5 4 3 2 1 0 0 0.2 0.4 0.6 tim e in hr 0.8 1 1.2 time in hr Linear (time in hr)
To obtain good correlation between in vitro- in vivo dissolution rate, In vitro is always carried out under sink condition.
Bathing the dissolving solid by fresh solvent from time to time. Increasing 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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drug. y Dissolution is said to be under nonsink condition. y Release rate equation for first order kinetics can be given by, Qt=Q0e Or In(Qt/Q0)=kt
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-Kt
relationship between drug release & time, plot of log of % drug remaining Vs time is plotted.
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If we plot a graph between conc. Of dissolved drug Vs. time is plotted. Fist order dissolution and Zero order dissolution under sink and nonsink condition are compared
time in hr
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Weibull Model
This model can successfully applied to all kinds of dissolution
curve. This model express the accumulated fraction of the drug m, in solution at time t,
` Equation can be given by,
a- Scale parameter define 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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Weibu
6 5 4 3 2 1 0 0 5 log of time
odel
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Disadvantage: It does not characterize the dissolution kinetic properties of the drug. Not any single parameter related with dissolution rate of drug
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Higuchi Equation
Explained release of water soluble & poorly water soluble Higuchi equation is mainly followed, when release
drug from variety of matrixes including semisolid & solid. of drug depend upon it s diffusion.
Mt / M0 = kt
1/2
Mt = amount of drug release in time t. M0 =Initial amount of drug release. t= time required.
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Hi uc i Equati n
y Hence plot of %
Hi uc i Equ i n 100
80 60 40 20 0 0 1 SQRT 2 3 % cumul d ug l
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dissolution is occurring then the dissolution occurs in plane that are parallel to the dosage form surface. 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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Hi
n Cr well cube r
t law
Hixs n-C
u 5 4
wel cube
t law
2 1 0 0 2 4 time in 6 8
c be r t ass r ss l e
cube
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! $ #! " !
Korsemeyer-Peppas equation
y Model for understanding release behavior of
Mt/M = Ktn Mt = amount of drug release in time t. M = amount of drug release in time . 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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Korsemeyer-Peppas equation
y Hence plot of log
log of
log of tim e
release mechanism.
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&0
(0
'0
20 %
2
.
2' '
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Korsemeyer-Peppas equation
n <0.5 0.5 0.5<n<1 1 n>1 lu Di usion c nis
Baker-Lonsdale Model
y Developed from the Higuchi model. y Describes the Drug controlled released from Spherical
y If matrix is heterogeneous
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Baker-Lonsdale model
5 4.5 4 3.5 3 2.5 2 1.5 1 0.5 0 0 1 2 3 tim e in r 4 5 6
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Hopfenberg Model
y The release of drug from surface-eroding devise with
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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time (l)is placed in the beginning of the drug release from pharmaceutical dosage form.
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that best fits the dissolution data was evaluated by comparing the correlation coefficient ( r ) values obtained in various models, the model that gave higher r value is considered as best fit model.
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parameter used to characterise drug release and gives information of drug release.
y tx%-time necessary to the release of a determined
percentage of drug. y Sampling time-amount of drug dissolved in that time. y Dissolution efficiency-
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1)Statistical method. a) Single time point dissolution. b) Multiple time point dissolution. 2)Model Independent 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).
It 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 procedureIt 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 procedureThis includes: 1)Difference Factor. 2) Similarity factor.
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1)Difference factor. It is the percent error between two curves all time points, denoted by f1.
over
n-sampling number. Rj-% dissolved of the reference product. Tj-% dissolved of the test product.
y The percent error is zero when test and reference profile are
identical.
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2)Similarity factory
It is logarithmic transformation of the sum- squared error difference between the test and reference product over all time points.
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Conclusion
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
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References
y Martin s physical pharmacy &pharmaceutical sciences,
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efere ces
` Evaluation of mathematical models describing drug
release from lipophilic matrices , journal of controlled release, august 2006,224-228. movement studies from matrices combining mixtures of swellable and inert polymers, International Journal of Pharmaceutics, September 2007, 61 73.
y www.dissolutiontech.com/DTresour/899art/dis
sprofile.html
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References
y Mathematical evaluation of in vitro release profiles
of hydroxypropylmethylcellulose matrix tablet containing carbamazepine associated to b-cyclodextrin, European Journal of Pharmaceutics and Biopharmaceutics ,May 2004, 177 179.
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