THEORY OF DRUG DISSOLUTION

Presented By
Rinoy R. K. Ist M. Pharm Pharmaceutics

Definition
Dissolution is a process separation solute molecule from solid solute and dispersion of molecule into the solvent to which solute has been added of the the the

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 dt
Where

=DAKw/o (Cs Cb)

dC dt = dissolution rate of drug D A

= thickness of stagnant layer

= Diffusion coefficient of drug = 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
Diffusion coefficient of drug Surface area of solid drug Water oil partition coefficient

Symbol
D

Influence on drug dissolution

Greater the value faster the dissolution Greater the surface area faster dissolution Higher value more hydrophilicity faster dissolution

A Kw/o

Thickness of stagnant layer

More the thickness less 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 = Ki (Cs-Cb)
G dissolution rate per unit area 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 DISSOLVED DRUG

ZERO ORDER, SINK CONDITION

Time