THEORY OF DRUG
DISSOLUTION
Presented By
Rinoy R. K.
Ist M. Pharm
Pharmaceutics
Definition
Dissolution is a process of
separation solute molecule from the
solid solute and dispersion of the
molecule into the solvent to which the
solute has been added
ie mass transfer from solid surface to
liquid phase
Dissolution of solid in a liquid may be
considered to be composed of two
consecutive stages,
1. Liberation of solute molecule from
the solid surface to stagnant diffuse
layer adjacent to solid surface and
2. The transfer of these molecules from
the boundary layer in to the bulk of
the liquid under the influence of
diffusion.
The overall rate of mass transfer is
decided by the step which is slower if
the rate of both the step are
comparable the overall mass transfer is
influenced by both the steps
The rate of dissolution of a solid in a
liquid is quantitatively given by the
Noyes Whitney equation
Several theories to explain drug
dissolution have been proposed
Some of the important once are
Diffusion layer model or Film theory
Danckwerts model or Penetration
or surface renewal theory
Interfacial barrier model or double
barrier or limited solvation theory
Diffusion layer model or Film theory
Simplest and most common theory for
dissolution
Here the process of dissolution of solid
particle in a liquid in the absence of
reactive or chemical forces
this explained in the basis two steps of
process
This process consist of two
consecutive steps:
Solution of solid to form a thin film or
layer at solid liquid interface called as
stagnant film or diffusion layer which is
saturated with drug this step is usually
rapid
Diffusion of soluble solute from
stagnant layer to bulk of solution this
step is slower so it is the rate
determining step in drug dissolution
Noyes and Whitney Equation
It explain rate of dissolution
based on Ficks IInd law
dc
= K(Cs - Cb)
dt
dc
= dissolution rate of drug
dt
where
K = Dissolution rate constant
Cs = Concentration of drug in stagnant layer
Cb = Concentration of drug in
bulk of solution at time t
Burner in corperated Ficks first law of
diffusion and modified the equation no. (1)
dc
=DAKw/o (Cs Cb)
dt
Where
dC
H = thickness of
dt = dissolution rate of drug stagnant layer
D = Diffusion coefficient of drug
A = Surface area of dissolving solid
Kw/o = water oil partition coeffient of drug
V = Volume of dissolution medium
Influence of various parameters on
dissolution rate of drug
Parameters Symbol Influence on drug
dissolution
Diffusion D Greater the value faster the
coefficient of dissolution
drug
Surface area of A Greater the surface area
solid drug faster dissolution
Water oil Kw/o Higher value more
partition hydrophilicity faster
coefficient dissolution
Thickness of H More the thickness less
stagnant layer dissolution
DANKWERT MODEL
(SURFACE RENEWAL THEORY)
Don't approve existence of stagnant layer
and suggest turbulence in the dissolution
medium exist at Solid/Liquid interface.
He suggest that the agitated fluid
consisting of macroscopic mass of eddies
or packets reach Solid/Liquid interface in a
random fashion due to eddy currents
solute is absorbed by diffusion and carry
into bulk of solution
Such solutes containing packets are
continuously replaced with new packets
of fresh solvent, so drug concentration at
Solid/Liquid interface never reaches Cs
and lower limiting value Ci.
Since solvent packets are exposed to new
solid surface each time. This theory is
called surface renewal theory
dc dm
V = = A (Cs-Cb) D
dt dt
rate of surface removal
m mass of solid dissolved
Interfacial barrier model
The Diffusion layer model
Danckwerts model
is based on two assumption
1. The rate determining step that controls
the dissolution in the mass transport
2. Solid dissolution equilibrium is
achieved at solid/liquid interface
According to interfacial barrier model:
an intermediate can exist at interface as
a result of solvation mechanism and it is
a function of solubility rather than
diffusion
When considering dissolution of crystals
each face of crystal will have a different
interfacial barriers such concepts given
by following equation
G dissolution rate per
unit area
G = Ki (Cs-Cb) Ki Effective interfacial
transport constant
Equation represents first order dissolution
rate process
The in vivo dissolution is always rapid
than in vitro dissolution, because the
movement of drug dissolves into
systemic circulation as a result Cb = 0
dissolution is at its maximum
Thus under in vivo condition there is no
concentration building up in the bulk
solution hence no retarding effect on
dissolution rate of drug ie. Cs>>Cb, Sink
condition are maintained
Under sink condition if the volume and
surface area of solid are kept constant
then equation became
dc
=K
dt
Now it follows zero order kinetics
Since condition can be achieved by:-
Bathening dissolving solid in fresh
solvent from time to time
Increasing the volume of distribution
of fluid
Addition of water miscible solvent
Eg: alcohol to dissolution fluid
By adding selected adsorbents to
remove dissolved drug
FIRST ORDER,
NON-SINK CONDITION
CONCENTRATION OF
ZERO ORDER, SINK CONDITION
DISSOLVED DRUG
Time
