Diffusion controlled release systems

Models of oral drug delivery

Session Objectives

By the end of this session, students will be able to:

       Explain different models of oral drug delivery

       Comment the mechanism of drug release in various oral delivery systems

       Apply the concepts of diffusion, dissolution, diffusion & dissolution in dosage form  development

Diffusion controlled release systems

Reservoir Devices

       These systems will offer zero order type of drug release

       Drug release are varied by the types of polymer used

       They should be removed physically from the implant site after treatment

       Incorporation of high molecular weight compound is difficult

       It’s expensive

dm/dt = ADK ∆c/L


A- Area

D- Diffusion coefficient

K- Partition coefficient

L- Thickness of coat

∆c- concentration difference across membrane


v  Zero-order delivery is possible

v  Release rate variable with polymer type


Ø  Removal of system from implants

Ø  Bad for high-molecular weight compounds

Ø  Cost

Ø  Potential toxicity if system fails

Reservoir Diffusional Products


Nico-400, Nitro-Bid, Nitrospan


       Consists of drug dispersed homogeneously throughout a polymer matrix

       Drug in the outside layer is exposed to the bathing solution is dissolved and diffuses out of the matrix

       This process continues with the interface between bathing solution and the solid drug moving toward the interior

Higuchi Equation

Q = DE/T(2A.E Cs)Cs.t)1/2


Q=amount of drug release per unit surface area at time t. 

D=diffusion coefficient of drug in the release medium.

E=porosity of matrix.

Cs=solubility of drug in release medium. 

T=tortuosity of matrix.

A=concentration of drug present in matrix per unit volume.

       In this systems drug is dispersed in an insoluble matrix , the drug release  depends on diffusion process but not on the solid dissolution process

       Easy to prepare when compared to the reservoir devices

       Drug of high molecular weight can be used

       Dose dumping is less likely to happen

       Zero order release is not possible

       Removal of residual matrix is necessary for implanted systems

       Hydrophobic matrices : PVC , EC ,

       Lipid matrices : carnauba wax with stearic acid

       Hydrophilic matrices : carbopol , sodium alginate


1)      Easier to produce than reservoir devices

2)      Can deliver high molecular-weight compounds 


1)      Cannot obtain zero-order release

2)      Removal of remaining matrix is necessary for implanted systems


Procan SR, Desoxyn-Gradumet,  Choledyl SA

Combination of Dissolution and Diffusion System

       Therapeutic systems will never be dependent on dissolution only or diffusion only

       Bioerodibile devices, however, constitute a group of systems for which  mathematical descriptions of release is complex

       Complexity of the system arises from the fact that, as the polymer dissolves, the diffusion path length for the drug may change. this  usually results in a moving-boundary diffusion system

       Zero-order release can occur only if surface erosion occurs and surface area does not change with time

Dissolution & Diffusion controlled release system

       Drug encased in a partially soluble membrane.

       Pores are created due to dissolution of parts of membrane.

       It permits entry of aqueous medium into core & drug dissolution.

       Diffusion of dissolved drug out of system.

       Ex- Ethyl cellulose & PVP mixture dissolves in water & create pores of insoluble ethyl cellulose membrane.

       The main feature is that the drug core is enclosed with a partially soluble  membrane

       Dissolution of part of the membrane allows for diffusion of the contained  drug through pores in the polymer coat

       Which permit entry of aqueous medium into the core and hence drug  dissolution, and allow diffusion of dissolved drug out of the system

Release profile of drug described by the following equation:

Release rate = AD(C1 – C2) / l


A= surface area

D= diffusion coefficient of the drug through the pore 

l= diffusion pathlength

C1 = concentration of the drug in the core

C2 = concentration of the drug in the dissolution medium

       Example of obtaining such a coating is using a mixture of ethyl cellulose with  PVP or methyl cellulose , later dissolve in water and creates pores in the  insoluble ethyl cellulose membrane

       The drug release from the system depends on:

a)      Solubility of drug exposed to media

b)      Solubility of hydrophilic polymer

c)       Degree of pore formation

d)      Intactness of insoluble polymer

e)      Permeability & diffusivity of polymer


  • Different types of controlled release systems are:  Dissolution system, Diffusion system, Dissolution & diffusion  system, Osmotic regulated system, pH regulated system, Ion  exchange controlled systems and Hydrodnynamically  balanced systems
  • Types of dissolution models are controlled and pulsed delivery systems. The drug release from dissolution controlled delivery  systems are dependent upon porosity ,wettability ,particle size & hydrophobic additives in the formulation
  • Drug release from diffusion controlled can offer zero order drug  release kinetics
  • Drug release from diffusion and dissolution controlled system is  depended on the:
    • Solubility of drug exposed to media
    • Solubility of hydrophilic polymer
    • Degree of pore formation
    • Intactness of insoluble polymer
    • Permeability & diffusivity of polymer

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