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DISSOLUTION TESTING
By
D.Narender
M.pharmacy 1 st
Semester
DEPARTMENT OF PHARMACEUTICS
UNIVERSITY COLLEGE OF PHARMACEUTICAL SCIENCES
KAKATIYA UNIVERSITY
OUT LINE
Definitions
Theories of Dissolution
Mechanisms of drug release
Wagner theory
Zero order release
First order release
Hixon -Crowel model
Higuchi model
Peppas model
Weibull model
Conclusion
Definitions:
Dissolution:
Dissolution is defined as a process in which a solid
substance solubilizes in a given solvent i.e. mass transfer
from solid surface to the liquid phase.
Dissolution rate:
Dissolution rate is defined as the amount of solute
dissolved in a given solvent under standard conditions of
temperature, pH, solvent composition and constant solid
surface area.
It is a dynamic process
The rate of dissolution of drug substance is determined by
the rate at which solvent-solute forces of attraction
Drug Dissolution Process
THEORIES OF DISSOLUTION:
3 Theories
1) Diffusion layer model / Film theory
2) Danckwerts model (penetration or surface renewal theory)
3) Interfacial barrier model (double barrier or limited solvation theory)
Diffusion layer model
Assumes that there is a stagnant layer or diffusion layer which is saturated with the drug at the
solid liquid interface.
From this stagnant layer, diffusion of soluble solute occurs to the bulk of the solution.
Cs Film boundary
S c
bulk
solution
Stagnant layer
Once the solute molecules pass the liquid film-bulk film interface rapid
mixing occurs and concentration gradient is destroyed. The rate of solute
movement and therefore the dissolution rate are determined entirely by the
Brownian motion diffusion of molecules in liquid film.
The rate of dissolution when the process is diffusion controlled is given by
noyes-whitney equation
Equation:
dC/dt =D.A.Kw/o (Cs Cb)\ v.h
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 drug
V = volume of dissolution medium
h = thickness of stagnant layer
CsCb = concentration gradient of diffusion of drug
Film boundary
Cs
S
C
Bulk solution
Stagnant layer
HighSolubility LowSolubility
(DoseVol.NMT (DoseVol.>250
250mL) mL)
Wagner theory
Wagner interpreted the percent dissolved time plots derived from
the in vitro testing of regular tablets and capsules.
this concept relates to the apparent first order kinetics under
sink conditions to the fact that a percent dissolved value at time
t may be equivalent to the percent surface area generated at same
time.
Wagner utilized the following mathematical method to desribe
his theory for the dissolution kinetics of conventional tablets and
capsules assuming that surface area available for dissolution
decreases exponentially with time according to the equation;
S = S0 e-ks ( t-to) -------------------------------->
1
Where So is the surface area at time to.
But we know that
dW/dt = K.S.Cs ------------------------(2)
Substitution for S from equation (1) ,we get
dW/dt = K.Cs.So.e-ks(t-to) ------------------------(3)
Integration of above equation gives
w= w0+K/ks Cs So [1-e-ks(t-to)] ------------------------(4)
If it is assumed that W is the amount in solution at infinite
time and M= K/ks.Cs.So,then
W = Wo+M and W-W = M e-ks(t-to) -------------------(5)
Applying log to both sides ,we get,
log (W - W) = log M ks/2.303( t to) ------------(6)
Where W - w is the amount of undissolved drug.
Zero order release:
Zero order refers to the process of constant drug release from a drug delivery
device such as oral osmotic tablets,transdermal systems,matrix tablets with low
soluble drugs
constant refers to the same amount of drug is released per unit time.
drug release from pharmaceutical dosage forms that donot disaggregate and
release the drug slowly can be represented by the following equation
W0 Wt = K .t ------------------- 1
W0 = initial amount of drug in the dosage form.
Wt = amount of drug in the pharmaceutical dosage form at time t
K = proportionality constant.
Dividing this equation by W0 and simplifying
ft = K0 .t
where ft = 1-(Wt/W0)
Ft = fraction of drug dissolved in time t and Ko the zero order release constnat.
A graphic of the drug dissolved fraction versus time will be linear.
Applications:
Zero order kinetic model can be used to describe the
drug dissolution of several types of modified release
pharmaceutical dosage forms, as in case of some trans
dermal systems ,as well as matrix tablets with low
soluble drugs, coated forms ,osmotic systems etc.
First order release:
If the amount of drug Q is decreasing at a
rate that is proportional to he amount of
drug Q remaining ,then the rate of release of
drug Q is expressed as
dQ/dt = -k.Q -----------------1
Where k is the first order rate constant.
Integration of above equation gives,
ln Q = -kt + ln Q0 ---------------- 2
The above equation is aslo expressed as
Q = Q0 e-kt ------------------------ 3
Inference
The pharmaceutical dosage forms following this
model, such as those drugs containing water
soluble drugs in porous matrices, release the drug
in a way that is proportional to the amount of drug
remaining in its interior.
b) When the drug particles are incorporated in granular matrix and released by
leaching action of penetrating solvent.
Higuchi demonstrated that during the initial release phase from a
spherical system until approximately 50% of drug content in vehicle
has been released,the square root of time behaviour is dominating and
then it depends on design of sustaine release system.
From Ficks first law,
dM/S.dt = dQ/dt = D.Cs/ h --------------------------(1)