Sei sulla pagina 1di 20

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