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

Where,

A- Area

D- Diffusion coefficient

K- Partition coefficient

L- Thickness of coat

∆c- concentration difference across membrane

Advantages

v  Zero-order
delivery is possible

v  Release
rate variable with polymer type

Disadvantages

Ø  Removal
of system from implants

Ø  Bad
for high-molecular weight compounds

Ø  Cost

Ø  Potential
toxicity if system fails

Reservoir Diffusional Products

PRODUCT

Nico-400, Nitro-Bid, Nitrospan

MATRIX DEVICES

       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

Where,

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

Advantages

1)      Easier
to produce than reservoir devices

2)      Can
deliver high molecular-weight compounds 

Disadvantages

1)     
Cannot obtain zero-order release

2)     
Removal of remaining matrix is necessary for
implanted systems

MATRIX DIFFUSIONAL
PRODUCTS

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

Where,

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

Summary

  • 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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