Theory of Dissolution.

1. THEORY OF
DISSOLUTION
P R E S E N T E D B Y,
A J AY L U N A G A R I YA
A C P 2 2 P H C E 0 0 2
D E PA RT M E N T O F
P H A R M A C E U T I C S
M . P H A R M S E M - 1 ( 2 0 2 2 - 2 3 )
1
P R E S E N T E D TO ,
D R . V E N K AT E S H D P
H O D & P R O F E S S O R
D E PA RT M E N T O F
P H A R M A C E U T I C S
A B M R C P

2. Definition :
2
Dissolution :
• Dissolution 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.
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.
• The rate of dissolution of drug substance is determined by the rate at which solvent-solute forces of
attraction overcome the cohesive forces present in solid.

3. 3

4. Theories Of Dissolution :
v Diffusion Layer Model / Film Theory
v Danckwert's Model / Penetration Or Surface Renewal
Theory
v Interfacial Barrier Model / Double Barrier Or Limited
Solvation Theory
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5. vDiffusion layer model / Film Theory :
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 (instantaneous).
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. The model is
depicted in following fig.
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6. 6

7. • The rate of dissolution is given by Noyes and Whitney:
dc = k (Cs- Cb)
dt
Where,
dc/dt= dissolution rate of the drug
K= dissolution rate constant
Cs= concentration of drug in stagnant layer
Cb= concentration of drug in the bulk of the solution at time t
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8. • Brunner & Tolloczko incorporated surface area „A" in Noyes &
Whitney equation.
dc = kA (Cs - Cb)
dt
• Afterwards Brunner, incorporated Fick's law of diffusion & expanded
his given eq to include diffusion coefficient,,D", thickness of stagnant
diffusion layer „h" & volume of dissolution medium,,v".
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9. • Modified Noyes & Whitney equation
dc = DAKw/o (Cs - Cb)
dt Vh
Where,
D = diffusion coefficient of drug.
A = surface area of dissolving solid.
Kw/o = water/oil partition coefficient of drug.
V = volume of dissolution medium.
h = thickness of stagnant layer.
(Cs - Cb) = conc. gradient for diffusion of drug. 9

10. • This eq describes a first-order dissolution kinetics. It represents dissolution
under non-sink conditions.
• If volume is relatively large such that
Cs>>>Cb so,
dc/dt =AKw/o Cs/Vh
• Cs & D are constant for each specific chemical substance so
dc/dt =k A/Vh
• V & A are kept constant during dissolution so, dc/dt =k
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11. v Sink condition :
• A Sink conditions describe a dissolution system that is sufficiently dilute so that the
dissolution process is not impeded by approach to saturation of the compound of
interest.
• Sink conditions affect the production of the sample but not the condition of the
solution upon sampling.
• In vivo condition, there is no conc. build up in the bulk of the solution and hence no
retarding effect on the dissolution rate of the drug i.e. Cs>>Cb and sink condition
maintain. 1 1

12. • Dissolution rate under sink condition follow zero order dissolution rate :
1 2
Conc
of
Dissolve
Drug
Zero order Dissolution
Under Sink Condition
First Order Under
Non Sink Condition
Time

13. • For obtaining IVIVC sink condition can be achieved by:
1) Bathing the dissolving solid in fresh solvent from time to time.
2) Increasing the volume of dissolution fluid.
3) Removing the dissolved drug by partitioning it from the aqueous phase of
dissolution fluid into the organic phase placed either above or below the
dissolution fluid for e.g. hexane or chloroform.
4) Adding a water miscible solvent such as alcohol to the dissolution fluid.
5) By adding selected adsorbents to remove the dissolution drug. In vitro sink
condition is so maintain that Cb always less than 10% of Cs.
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14. • This theory assumes that solid-soln equilibrium is achieved at interface and mass transport is
slow step in dissoln 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. Acc. 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.
• Diffusion occurs into each of these packets during short time in which the packet is in contact
with surface of solid.
• Since turbulence actually extends to surface, there is no laminar boundary layer and so no
stagnant film exists. Instead, surface continually being replaced with fresh liquid.
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v Danckwert's Model / Penetration Or Surface Renewal Theory

15. vDanckwert's Model / Penetration Or Surface
Renewal Theory
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16. 1 6
The Danckwert's model is expressed by equation :
Where,
m = mass of solid dissolve
y = rate of surface renewal
Cs-Cb = conc. gradient for diffusion of drug.

17. vInterfacial Barrier Model / Double Barrier Or
Limited Solvation Theory
• The diffusion layer model and Danckwert's model were based on two
assumptions:
1. The rate determining step that controls dissolution is the mass transport.
2. Solid-solution equilibrium is achieved at the solid/liquid interface. According
to the interfacial barrier model, an intermediate concentration can exist at the
interface as a result of solvation mechanism and is a function of solubility
rather than diffusion.
• When considering the dissolution of a crystal, each face of crystal will have a
different interfacial barrier. 1 7

18. • Cont....
Such a concept is given by the following equation:
G= Ki(Cs-Cb)
where,
G = dissolution rate per unit area
Ki = effective interfacial transport constant
Cs-Cb = conc. gradient for diffusion of drug.
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19. Reference :
1. Brahmankar D.M., Jaiswal S.B. (2009), "Biopharmaceutics and Pharmacokinetics-A
Treatise" Vallabh Prakashan, 2nd Edition, page no. 15-48
2. Government of Indian ministry of health and family welfare (2014), "Indian
Pharmacopoeia" Indian Pharmacopoeia commission, Ghaziabad, Volume-1, Page No.
174
3. Banakar U.V. (1992), "Pharmaceutical Dissolution Testing" Informa Healthcare, 1st
Edition, page no. 1-30
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20. Thank You
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