Chap. 1.

Controlled drug
delivery system
Presented by
Ghanshyam.V.Patel
M.Pharm (I.P)

1
DIFFERENCE BETWEEN
ZERO ORDER CDDS AND
FIRST ORDER SRDF

Y
Plasma Drug Concentration

Max Safe Con

CR (ZERO ORDER)

Min Effect Con

SR (FIRST ORDER)

Sing Dose of Conventional tab

X
o TIME
Plasma Drug Concentration v/s Time

2
 Definition of Microencapsulation
It is the process of applying relatively thin
coating polymer to small particles of solids
or droplets of liquids and dispersions.

These polymers are inert, do not readily

biodegradable, have good tissue
biocompatibility.

Drug release mechanism across

membrane into surrounding by diffusion .

Polymers: ethyl cellulose, poly vinyl acetate.

3
Advantages:
1. Masking of unacceptable taste or order of drug.
2. Liquid can be converted into free flowing solid/powders.
3. Stabilization of drug sensitive to oxygen, moisture or
light.
4. Prevention of vaporization of volatile drug.
5. Reduction of toxicity and to reduce gastrointestinal
irritation.
6. Alteration in site of absorption.
7. Drug release control by adjusting the thickness and
permeability of the coat
8. Coated particles : compressed into tablet or placed in
capsules
9. Zero order delivery is possible; release rate varies with
polymer type

4
Disadvantages:
1. System must not be physically removed
from implant sites.
2. Difficult to deliver high molecular weight
compound.
3. Increased cost per dosage unit.
4. Potential toxicity if system fails.
5. Incomplete or discontinuous coating.
6. Clumping of microencapsulation.
Ficks first law of diffusion describes the
diffusion process.
J= - D dc/dx.
D = diffusion coefficient in area/ time
dc/dx = change of concentration 'c' with
distance 'x'
5
Methodology for micro encapsulation
General Classification
 Air suspension
 Coacervation phase separation
 Spry drying
 Congealing
 Pan coating
 Vacuum deposition
 Polymerization
 Multiorifice centrifugal process

6
Microencapsulation Technologies
Physical Methods of Encapsulation
 Spray drying
 Spray chilling
 Rotary disk atomization
 Fluid bed coating
 Stationary nozzle coextrusion
 Centrifugal head coextrusion
 Submerged nozzle coextrusion
 Pan coating
Chemical Methods of Encapsulation
 Phase separation
 Solvent evaporation
 Solvent extraction
 Interfacial polymerization
 Simple and complex coacervation
 In-situ polymerization
 Liposome technology
 Nanoencapsulation

7
 (A) Air suspension
Principle:-
To disperse solid core materials in a
supporting air stream and spray coating
material on air suspended particles.
Method:-
The particles are suspended on an upward
moving air stream as each pass through the
coating zone, the core receives an increment of
coating material.
The cyclic process is repeated several hundred
time depending upon the coating thickness
desired.
The supporting air stream serves to dry the
product while it is being encapsulated. 8
 Fig. Air Suspension Equipment

9
 Factors which effect encapsulation process

 Coating material concentration.

 Coating material application rate.
 Volume of air required to support the core
material.
 Amount of coating material required.
 Inlet and outlet operating temperature.
 Density, surface area, melting point,
solubility, friability, volatility, crystallinity and
flow ability of core material.

10
 (B) Coacervation phase separation
General method
Three steps
1. Formation of three immiscible phases

2. Deposition of coating

3. Rigidization of coating

11
Schematic representation
i) Polymer phase ii) Core phase

iii) Liquid vehicle phase

Formation of three immiscible phases

Phase separation is done by various method

Deposition is done by controlled agitation

Deposited core

Rigidization is done by Thermal, cross

linking, Desolvation

Micro encapsulation

12
 Phase separation is done by
1. Temperature change method.
2. Incompatible polymer addition.
3. Non solvent addition.
4. Salt addition.
5. Solvent evaporation techniques
6. Polymer-polymer interaction

13
1. Temperature change method.

Temp change

14
 The fig show a general temp-composition phase
diagram for binary system composed of a polymer & a
solvent.
A system having an overall composition, represented
as point X on abcissa, exist as single phase, homogeneous
solution at all points above the phase-boundary or binodal
curve FEG.
As the temp of the system is decrease from point A
along the arrowed line AEB, the phase boundary is
crossed at point E & the two phase region is entered.
Phase separation of dissolved polymer occurs in the
form of immiscible liquid droplets, if a core material is
present in the system, under proper polymer
concentration, temp and agitation conditions, the liquid
polymer droplets coating around dispersed core particle
& thus forming embryonic microcapsules. 15
E.g. Coat -------Ethyl cellulose
Core--- ----Paracetamol
Solvent–--Cyclohexane.
Method:-
First ethyl cellulose is suspended
in Cyclohexane & slowly increase
temperature (50 to 60).
Ethyl cellulose is solubilized then
disperse paracetamol.
There are 2 phase. Then slowly
cool the mixture it forms 3 Phase.
16
2. Incompatible polymer addition.
Liquid phase separation of a polymeric coating
material and micro encapsulation can be
accomplished by utilizing incompatible polymer.
E.g. Coat ----Ethyl cellulose
Core ------Methylene blue hydrochloride
Vehicle---Toluene
Incompatible polymer--- Liquid poly butadiene
Method:-
Liquid poly butadiene quite soluble in toluene &
incompatible with ethyl cellulose.
liquid poly butadiene displaces ethyl cellulose
from toluene subsequent microencapsulation.

17
3. Non solvent addition.
A liquid that is a non-solvent for a given polymer can be
added to a solution of the polymer to induce phase
separation.
Coat-------------Cellulose acetate butyrate
Core-------------Methyl scopolamine hydrobromide
Vehicle----------Methyl ethyl ketone
Non-solvent----Isopropyl ether
Method:-
Polymer is dissolved in methyl ethyl ketone.
To it micronized methyl scopolamine hydrobromide
add & dispersed with stirring.
The resulting mixture is heated to 550C.
Isopropyl ether is added slowly to effect phase
separation then subsequently microencapsulated core
material.
18
 4. Salt addition.
Soluble inorganic salts can be added to aqueous solution
of certain water soluble polymers to cause phase separation.
E.g Coat-------------Gelatin
Core-------------Oil soluble Vitta-A
Vehicle----------Corn oil
Salt---------------Na2So4
Method:-
An oil soluble Vitta-A is dissolved in corn oil & is
emulsified to desired drop size in 10% solution of high
quality gelatin at 50oC.
Then slowly add 20% solution of Na2So4 with continuous
string.
This result in to microencapsulation of oil globules with
uniform coating of gelatin.

19
5. Solvent evaporation techniques
Method:-
Coating polymer is dispersed in a volatile solvents
which is miscible with the liquid manufacturing vehicle
phase.
A core material (drug) is dissolved in the coating
polymer solution.
With agitation the core material mixture is dispersed
in the liquid manufacturing vehicle phase to obtain
appropriate size microcapsule.
The mixture is then heated to evaporate the solvent
for the polymer.
Polymer shrinks around the core.
The core material may be water solubel or water
insoluble.
20
6. Polymer-polymer interaction
The interaction of oppositely charged
polyelectrolyte can result in the formation of a
complex having such reduced solubility that phase
separation occurs.
Method:-
Aqueous solution of gum arabica and gelatin are
prepared.
Then both polymer solution are mixed together
in equal amounts, then methyl salicylate is added
& mixed.
Then dilute to about twice their volume with
water, adjusted to pH 4.5 & warmed to 40oC.
Finally Cool solution at 25ºC & 10ºC,So Phase
Separation is Done.

21
Release mechanism from microencapsulation

22
 Applications
1. Preparation of sustained release or prolonged
release medications.
2. To mask the bitter taste of medication.
3. To prevent incompatibility.
4. Increase stability.
5. Drugs which are liquid at room temp and undergo
oxidation can be microencapsulated e.g. Vit-A.
6. Protection against atmospheric moisture and other
reactions.
7. Protect against side effect like gastric irritation
e.g. KCl
8. To reduce the volatility of the drugs
e.g Methyl salicylate (Liquid).
9. To improve shelf-life.
23