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 contents

1. Introduction
2. Fick¶s law of diffusion
3. Noyes -Whitney¶s equation
4. Various steps involved in dissolution
5. Limitations
6. Sink and non sink conditions
Introduction:
! Dissolution is a process by which a solid drug
substance become dissolved in solvent.

! It¶s a dynamic property.

! Drug dissolution is important before prior to

systemic absorption.

! Various factors effecting dissolution of solid oral

dosage form includes ,
1. Physical and chemical nature of active drug
substance.
2. Nature of excipients
3. Method of manufacture
4. Type of formulation

! Permeation of a drug across gut wall (lipid

membrane)is affected by

å Partition coefficient between lipid membranes.

å Temperature of the medium(invivo temp is 37* ).

If temperature is increased then kinetic energy
of molecules increases and diffusion rate constant D
increases

å Agitation rate should be kept constant. If it is

increased then stagnant layer thickness is decreased .
This in turn allows more dissolution of the
drug.

å Ability of drug to diffuse

Fick¶s second law of diffusion:
! It states that ³Rate of change of concentration of
dissolved material with time is directly proportional
to concentration difference between 2 sides of
diffusion barrier´.
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 Noyes Whitney equation:
! It is used to define dissolution from a from a single
spherical molecule.

dw/dt rate of dissolution

D diffusion rate constant
A Particle surface area
Cs Concentration of drug in stagnant
layer
Cb concentration of drug in bulk solvent
L Thickness of diffusion layer
!.
! According to this theory the stages involved in the
dissolution are,
Stage 1:
! An interfacial reaction occurs which result in
liberation of solute molecules from solid phase.

! Drug dissolution occur at the surface of the solid

particle.

! A saturated layer is formed around the particle i.e

stagnant layer formation.

! This stage is rapid

Stage 2:
! Solute molecules migrate through the boundary
layers surrounding crystal to bulk of solution at
which its conc is Cb

! This step involves in transfer of molecule away from

solid liquid interface into bulk of liquid phase.

! It is a slow step and hence it is a rate limiting step.

! Limitation:
1. This theory assumes that surface area of
dissolving solute remain constant during
dissolution but practically it is not possible.

! Hixon and Crowell modifies the above equation

to explain the effect of change of surface area.
! w01´ 1

   

  
  
    
 

  
   

! Non sink condition:

1. Invitro dissolution represent first order process for

which driving force is concentration gradient.

2. It is true for invitro dissolution in a limited

dissolution medium.

3. Dissolution slows down after some time due to

increased drug concentration in bulk of the solution.
Sink condition:
! It is rapid than compared to invitro because the
moment drug dissolves it is absorbed into systemic
circulation, so Cb is zero.

! And Cs>>Cb so no concentration is build up in bulk

of solution.

! If the volume and surface area is kept constant then

above equation reduces to
dc/dt 
! Dissolution is constant under sink conditions and
follows zero order kinetics i.e yield linear plot
! To obtain invitro and invivo dissolution rate
correlation ,the invitro dissolution carried out under
sink condition. It is achieved by,

1. Bathing the dissolving solid in fresh solvent from

time to time.

2. Increase the volume of dissolution.

3. Partitioning of drug from aqueous phase into

organic phase E.g: chloroform, heptane
! Adding water miscible solvent like alcohol to
dissolution fluid.

! Adding selected absorbents to remove dissolved

drug.

! To maintain Invitro sink condition Cb should always

less than 10% of CS.
 References

! Biopharmaceutics and pharmacokinetics by

brahmankar,B.jaiswal and shargel.

! Remington -science and practice of pharmacy 21st

edition
! www.authorstream.com
! www.4reen.com
m