A Seminar on

Control Release Oral Drug Delivery System

By:
Uday Sharma
Dept. of Pharmaceutics
Al Ameen college of Pharmacy

Contents
Introduction
Advantages & Disadvantages
Design and Fabrication of Oral Systems
Dissolution controlled release
Diffusion control release
Diffusion & Dissolution controlled release
Ion exchange Resins
pH independent formulation
Osmotically controlled release
Hydrodynamically balanced system

Introduction
Controlled release describes a system in which
the rate of drugs release is more precisely
controlled compared to sustained release product
or
Delivery of the drug at predetermined rate or /to a
location according to the need of the body / disease
state for a definite time period.

Drug delivery systems refer to the technology

utilized to present the drug to the desired body site
for drug release and absorption

Advantages of oral controlled-release

Decreased fluctuation in circulating drug levels, resulting in
reduced toxicity and sustained efficacy
Decreased frequency of dosing.
Increased patient compliance.
Avoidance of night time dosing

Reduced patient care time.

Reduction in GI irritation

Disadvantages of oral controlled-release

Longer time to achieve therapeutic blood concentrations.

Increased variation in bioavailability.

Enhanced first-pass effect.
Dose-dumping.
Sustained concentration in overdose cases.
Lack of dosage flexibility.

Greater expense.

Properties of drug not suitable for controlled-release

formulation
Very short or very long half-life.
Narrow therapeutic window.
Poor absorption
Low solubility.

Drug concentration not related to pharmacologic or therapeutic

effect.
Extensive first pass clearance.

Design and Fabrication of Oral Systems

Dissolution controlled release
Diffusion controlled release
Diffusion & Dissolution controlled release
Osmotically controlled release
Hydrodynamically balanced system device

pH independent formulation
Hydrodynamically balanced system

Ion exchange Resins

Dissolution controlled Release

Simplest to prepare.

Drug with a slow dissolution rate is inherently sustained.

Example: digoxin, griseofulvin, salicylamide.

Drugs which produce slow dissolving form when come in

contact with G.I fluid or absorption pool.
Example: aluminum aspirin, ferrous sulfate.

Principle
The rate of diffusion from the solid surface to the bulk solution :
rate limiting

Flux= (diffusion coefficient) x (concentration gradient)

J = - D (dc / dx)
OR
Flux = flow rate of material (dm / dt ) through a unit area ( A )
J = ( 1 / A ) dm / dt
If the concentration gradient is linear and thickness of the
diffusion layer is h
dc / dx = ( Cb Cs ) / h
Where: Cs concentration at solid surface.
Cb concentration in the bulk solution.

Combining the above equation

Flow rate of the material is given by:
dm/dt = - ( D A /h ) ( Cb Cs ) = kA (Cs Cb)
Where
k Intrinsic dissolution rate constant.
This equation predicts constant dissolution rate, if all
variables are constant.

Dissolution controlled system is of two type

En-capsulation dissolution control.

Matrix dissolution control.

Encapsulation Dissolution control

Drug coated with slowly dissolving polymeric material

Drug release control by adjusting the thickness and

dissolution rate of membrane
Membrane-coated particles: compressed into tablet or placed
in capsules.
Encapsulation dissolution control is of two types:
microcapsulation
Seed or granules coated products.

MICROCAPSULATION
Defined as a means of applying relatively thin coatings to small
particles of solid or droplets of liquids and dispersions
Provides a means of converting liquids to solids,

altering colloidal and surface properties,

providing environmental protection,

controlling release characteristics or availability of coated

material

example:
Aspirin encapsulated for

Taste-masking
Sustained release
Reduced gastric irritation
Separation in case of incompatibilities-such as
CPM

Applications
Sustained release
Taste masking chewable tablet
Powders and suspensions
Single layered tablets containing chemically incompatible
ingredients
New formulation concepts for creams, ointments, aerosols,
dressings, plasters, suppositories and injectables

Drawbacks
Incomplete or discontinuous coating.
Inadequate stability or shelf life of sensitive pharmaceutical
products.
Non reproducible and unstable characteristic of coated
product.

Economic limitation.

Polymers for micro-encapsulation

Water-soluble resins
Water-insoluble resins
Waxes and lipids

Water-soluble resins
Gelatin

Povidone (PVP)
CMC
HEC

MC
PVA

Water-insoluble resins
Ethyl cellulose
Polyamide (Nylon)
Polyethylene
Cellulose nitrate

Waxes and lipids

Paraffin
Carnauba

Beeswax
Stearic acid
Stearyl alcohol

Methods of micro-encapsulation
Pan coating

Air suspension coating

Coacervation-phase separation
Spray drying and congealing
Multi-orifice centrifugal
In-situ-polymerization

Pan Coating
Consists of applying coating solution to the
solid core material in a coating pan

Core material can be NPS or granules or

particles or particles greater than 600 in size

Air Suspension

Also called Wurster process

Consists of dispersing of solid, particulate core

materials is a supporting air stream and spraycoating of air-suspended particles

Process variables
Physical properties of core material
Concentration of coating material
Application rate of coating material
Volume of air
Amount of coating material required

Inlet and outlet operating temp

Applications
Wide variety of coating materials can be applied
Solvent solutions
Aqueous solutions

Emulsions
Dispersions etc
Air suspension coating is applicable to both microencapsulation and macro-encapsulation

Coacervation-Phase Separation
Consists of three steps carried out under constant agitation:
Formation of three immiscible chemical phases

Deposition of coating and

Rigidization of coating

Step 1
Formation of three immiscible chemical phases:
A liquid manufacturing vehicle phase

A core material phase

A coating material phase

To form the three phases,

Core material is dispersed in a solution of
coating polymer. The solvent used is liquid
manufacturing vehicle phase

The coating material phase is the immiscible polymer

in liquid state is formed by utilization of one of the
methods of phase separation Coacervation:
By changing temp of polymer solution
By adding a salt
By adding a non solvent

By adding incompatible polymer to polymer solution

By inducing a polymer-polymer interaction

Step 2
Consists of depositing the liquid polymer
coating upon core material

Accomplished by controlled, physical mixing of

the coating material (while liquid) and core
material in the manufacturing vehicle

Deposition of liquid polymer coating around the core

material occurs if polymer is adsorbed at the interface
formed between the core material and the liquid
vehicle phase

Continued deposition of coating material is promoted

by a reduction in the total free interfacial energy of
system brought about by decrease of coating material
surface area during coalescence of liquid polymer
droplets

Step 3

Involves rigidizing the coating, usually by

thermal, cross-linking or desolvation
technique, to form a self-sustaining
microcapsule

Temperature Change

Consists of forming a polymer solution at high temp. into which

insoluble drug core material is suspended.
As temp. is reduced, under controlled conditions of agitation,
phase separation of the dissolved polymer occurs in form of
immiscible liquid droplets which coalesce around the dispersed
core material particles, thus forming the embryonic
microcapsules

Example
Microencapsulation of paracetamol with ethylcellulose(EC)
Process
EC is soluble in cyclohexane at
60C and insoluble at RT
EC is dissolved in cyclohexane at high temp.

Fine divided drug added with continuous agitation

Allow mixture to cool with continuous stirring. This results in

phase separation/coacervation of EC and microencapsulation
of paracetamol

Further cooling to RT accomplished gelation and solidification of

coating

Microcapsules collected by filtration, decantation or centrifugation

Incompatible Polymer Addition

Principle
Liquid phase separation of polymeric coating material and
microencapsulation can be accomplished by utilizing the
incompatibility of dissimilar polymers existing in a common
solvent
Example:
The microcapsulation of methylene blue hydrochloride with ethyl
cellulose by this mode of phase separation ( incompatible
polymer addition)

NON SOLVENT ADDITION

A liquid that is a non solvent for a given solvent for a

given polymer can be added to a solution of a polymer
to induce phase separation . The resulting immiscible ,
liquid polymer can be utilized to effect
microcapsulation of an immiscible core material.

SALT ADDITION
Soluble inorganic salt can be added to aqueous
solution of certain water soluble polymer to cause
phase separation.

Example : oil soluble vitamin microcapsulation induced

by adding sodium sulphate.

Polymer Polymer interaction

The interaction of oppositely charged polyelectrolyte
can result in the formation of complex having low
solubility which leads to phase separation.

Example:
Gelatin and gum Arabic

Spray drying / spray congealing

spray dryers offer particle sizes of dried material from 50-250

microns.
For producing large particles Fluidized Spray Dryers are
employed.
The atomization of the feed solution is done to produce large
droplets
The moist powder is dried in the integrated fluid bed system at
the bottom of the drying chamber using hot air.

Seed or granules coated products

Wide range of drugs are formulated.

Process
NPS is coated with the drug solution.
th or 1/3 rd seed are coated with the drug which release

immediately.
Remaining th or 2/3 rd seeds are coated , by dividing into the
groups with coats of coating material to various thickness to
produce the effect for desired period.
Example :
Amobarbital & dextroamphetamine sulphate

Matrix dissolution control

Drug is sealed or embedded in the wax
material.

Method of preparation:
1. Aqueous dispersion
2. congealing

Aqueous dispersion :
Spraying or placing the wax drug mixture in water &
collecting the resulting particles.

Congealing method
Drug is mixed with the wax material & either spray
congealed or just congealed & screened.

Principle
The rate of drug availability is controlled by the rate
of penetration of dissolution fluid into the matrix.
Thus rate can be controlled porosity of tablet matrix,
i.e. presence of hydrophobic additives & particles
size.