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Classification various approaches





Drug delivery System will deliver
the drug at a rate determined by the needs of the
body over a specified period of time.



Control release is helpful for
maintaining constant drug levels in the target tissues
or cells.




1) Dissolution controlled systems

a) Encapsulation dissolution controlled system.
b) Matrix dissolution controlled systems.
2)Diffusion controlled systems
a) Reservoir controlled systems.
b) Matrix controlled systems.
3)Dissolution and diffusion controlled release



4)Water penetration controlled systems

a) Swelling controlled systems

b) Osmotically controlled systems.


5) Chemically controlled release systems

a) erodible systems

b) drug covalently linked with polymer


6) Hydro gels


7) Ion – exchange resin controlled release systems



Diffusion systems are characterized by – release rate
of drug is dependant on its diffusion through inert
water insoluble membrane barrier.

There are basically two types of diffusion

a) Rreservoir diffusion system – a core of
drug is surrounded by a polymeric membrane.

b) Matrix diffusion system – these are
systems in which dissolved or dispersed drug
distributed uniformly in an inert polymeric matrix.



2)Reservoir type Diffusion controlled system

 These systems are hallow containing an inner core of drug

surrounded in a water insoluble polymer membrane.

 The polymer can be applied by coating or microencapsulation

techniques .

 Mechanism ….partitioning the drug in to the membrane with

subsequent release in to surrounding fluid by diffusion.

 Polymers ….HPC, ethyl cellulose, methyl cellucose, polyvinyl


 Disadvantage is dose dumping



Schematic representation of diffusion sustained drug
release: reservoir system



Equilibrium between membrane surface & their bathing
solutions shown

Reservior diffussional device




Reservoir type: name implies process of diffusion described by fick’s law

It postulates that the flux goes from regions of high concentration to

regions of low concentration, with a magnitude that is proportional to

the concentration gradient. The law is

J= – D dCm/dx.

J- flux of drug across a membrane in the direction of decreasing conc.


D = diffusion coefficient in area/ time

dCm/dx = change of concentration ‘c’ with distance ‘x‘



Conc. just inside membrane surface can be related to conc. in
adjacent region by following expression,

K = Cm(o)/C(o) at x = 0
K = Cm(d)/C(d) at x = d
K – Partition coef.
Cm(o) – conc. of drug inside mem.
Cm(d) – conc. outside surface
d – thickness of diffusion layer

D & K are cont. eq. become

J = DK Δc/d
Δc – conc. diffusion



 drug release depend on geometry of system
– slab

In this case equation written as,
where, Mt – mass of drug release after time ‘t’
dMt/dt – steady-state release rate at time ‘t’

A – surface area.
This equation suggest that the drug molecules release under the

diffusion layer limiting partition controlled process & the drug release
rate is linearly proportional to product of solution concentration &
solution diffusivity Ds & is inversely proportional to the thickness of

1 hydrodynamic diffusion layer dd.


 Common method used to develop this system is

microencapsulation of drug particles and film coating of


 E.g. For oral route – Nitrospan capsule – nitroglycerin

For parenteral – norplant – levonorgestral implant

For ocular- vitrasert for ganciclovir implant

Transdermal – transderm scop – for scopolamine



A] Reservoir Diffusion sustained system:
 Basically diffusion process

Flux of the drug ‘J’

– by Fick’s law

J= – D dCm/dx.

D = diffusion coefficient in area/ time

dCm/dx = change of concentration ‘c’

with distance ‘x‘





– water insoluble membrane

drug release rate dm/ dt is given by

dm/ dt = ADK ∆C/L


A = area

K = Partition coefficient of drug between

the membrane and drug core

L = diffusion path length

[i.e. thickness of coat]

Dc = concentration difference

across the membrane.




2) Matrix type Diffusion controlled system

– solid drug is dispersed in an insoluble matrix

– drug release from matrix system depend on rate of diffusion and
given by Higuchi equation.

Schematic representation of diffusion sustained drug release: matrix



Drug is dispersed in insoluble matrix of rigid non swell
able hydrophobic materials.
Like insoluble plastics (PVC, fatty materials)

Popular for sustaining the release of highly water soluble
The materials for such matrices are generally hydrophilic
gum and may be of natural origin( guar gum, tragacanth),
semi synthetic (HPMC, CMC, Xantham gum)or synthetic
-the drug and gum are granulated together with a solvent
such as alcohol, and compressed in to tablet



The release mechanism…

……… the release of drug from the Swellable matrix system initially

dehydrated hydrogel involves continuous absorption of water (resulting in

hydration, gelling and swelling of gum) and desorption of drug via a

swelling controlled diffusion mechanism. And forms Glassy hydrogel.




 Derivation of the mathematical model to describe this system
involves the following assumptions

In this model it is assumed that solid drug dissolves

from the surface layer of the device first; when this

layer becomes exhausted of the drug, the next layer

begins to be depleted by diffusion through the

matrix to the external solution. In this fashion, the

interface between the region containing dissolved

drug and that containing dispersed drug moves into

1 the interior as a front.


The assumptions made in deriving mathematical model are

A) pseudo-steady state is maintained during drug release,

b) The diameter of the drug particles is less than the average

distance of drug diffusion through the matrix,

c) The release medium provides sink conditions at all times.

d) The total amount of drug present per unit volume in the matrix, C0 is substantially greater

than saturation solubility of the drug per unit volume of the matrix Cs

e) The diffusion coefficients remains constant.

f) No interaction occurs between drug and matrix.




Release behavior for the system described by“ Higuchi

The change in amount of a drug released per unit area, dM,

with a change in the depleted zone thickness, dh is

dM = Co·dh – (Cs/2). dh ————-1


dM = Change in the amount of drug released per unit area

dh = Change in the thickness of the zone of matrix that has

been depleted of drug

Co = Total amount of drug in a unit volume of matrix

Cs = Saturated concentration of the drug within the matrix.




Additionally, according to diffusion theory,

dM = (Dm.Cs) dt /h ———————2


dM = Change in the amount of drug

released per unit area

Dm = diffusion coef. in matrix.

Cs = Saturated concentration of the drug

within the matrix.



combining both equation and solving for h and equation for M is

M = [Cs . Dm . (2 Co – Cs ). t ]



M= kt1/2………(Cs . Dm . (2 Co – Cs )
1/2 = k)

Equation indicates the amount of drug release is proportional to

the square-root of time.

K is constant so that a plot of amount of drug release Vs square root

of time should be linear if release of the drug from the matrix is

diffusion controlled.

2 Release rate is not zero order since it decreases with time.



If the release of drug from matrix is diffusion-controlled. In this case,
the release of drug from a homogeneous matrix system can be
controlled by varying the following parameters,


• Initial concentration of drug in

the matrix

• Porosity

• Polymer system forming the


• Solubility of the drug



 Most common method is to mix the drug with the matrix
material and then compress the mixture into tablets.

 Disperse drug in molten waxes which is then congealed,
granulated and compressed into cores.

 Matrix tablet- contains priming dose in coat of tablet. Coat
applied by pan coating or air suspension technique.

 Oral desoxyn- metamphetamine

 Procaine for procainamide HCl

 Parenteral – compudose subdermal for estradiol

 Transdermal deponit for nitroglycerin.



A) Dissolution controlled release

In dissolution controlled systems, the rate

controlling step is dissolution. the drug is embedment

in slowly dissolving or erodible matrix or by coating

with slowly dissolving substances.

It is of two types and they are

Encapsulation dissolution controlled system

Matrix dissolution controlled system





The drug present in such system should be one

-With inherently slow dissolution rate…..
Ex. Griseofulvin , Digoxine.

-They produce slow dissolving forms when it comes in contact with GI
Ex. Ferrous sulphate.

-High aqueous solubility & dissolution rate.
Ex. Pentoxifylline.



The technique employed are
=embedded in slowly dissolve erodible matrix
=encapsulation or coating with slowly dissolving or erodible substance



1) Matrix type Dissolution controlled system

•Also called as monoliths
•Drug is homogeneously dispersed through out a rate controlling medium.
•They are very common and employ waxes such as bees wax, carnauba wax,
hydrogenated castor oil etc.



Matrix systems are also called as monoliths since the drug is
homogeneously dispersed throughout a rate controlling

 They employ waxes such as beeswax, carnauba wax,
hydrogenated castor oil etc which control drug dissolution by
controlling the rate of dissolution fluid penetration into the
matrix by

1. Altering porosity of tablet.
2. Decreasing its wettebility.
3. Dissolving at slower rate.
4. Exhibit First order drug release.
5. Drug release determined by dissolution rate of polymer.
The wax embedded drug is generally prepared by

dispersing the drug in molten wax and congealing and
granulating the same.



2)Reservoir type Dissolution controlled system

Thickness 1 to 200

Drug particles are coated or encapsulate with polymers such as cellulose, PEGs ,
PMC, and waxes.
The resulting pellets may be filled as such in hard gelatin capsule ( Spansule) or
compressed in to tablet.

Rate controlling factor:
-solubility of coat
-thickness of coat



 The drug particles are coated or encapsulated by

microencapsulation techniques with slowly dissolving

materials like cellulose, poly ethylene glycols,

polymethacrylates, waxes etc. the dissolution rate of coat

depends upon the solubility and thickness of the coating.




 Dissolution process described by
Noyes-whitney equation

dc/dt = Kd A (Cs-C)

= D/h A (Cs-C)
dc/dt – dissolution rate
Kd – dissolution rate const.
D – diffusion coef.
Cs – saturation solubility of solid
C – conc. Of solute in bulk



 The above equation predicts a constant dissolution rate if the
surface area, diffusion coefficient, diffusion layer thickness and
conc. Difference are kept constants.

 However, as dissolution proceeds, all of these parameters may
change, especially surface area.

 For spherical particle, the change in area can be related to the
weight of the particles; under assumption of sink conditions;
equation becomes

W 1/3
0 – W 1/3 = Kd .t


 Where kd is the cube root dissolution rate constant

W0 initial weight

W weight of amount remaining at time t.


Water Penetration Controlled Systems

In water penetration controlled delivery systems,
rate control is obtained by the penetration of water
into the system. They are

 Swelling Controlled Systems:-
Swelling controlled release systems are initially

dry and when placed in the body absorb water or other
body fluids and swell. Swelling increases the aqueous
solvent content within the formulation as well as the
polymer mesh size, enabling the drug to diffuse
through the swollen network into the external



“a” indicates reservoir diffusion swelling.
“b” indicates matrix diffusion swelling.




 Chein YW. Novel drug delivery systems. 2nded,pg:139-30
 Brahmankar. Biopharmaceutics and pharmacokinetics .

5thed, pg: 350-25
 Edith Mathiowitz. Encyclopedia of controlled drug delivery.

1sted, Vol.II, pg: 698-29.
 Wise DL. Hand book of pharmaceutical controlled release

technology. 1sted, pg: 183-24.
 Tamizharasi S, Rathi JC, Rathi V. Formulation and

evaluation of Pentoxifylline-loaded Poly(ἑ-caprolactone)
microspheres . Ind J of Pharm Sci, 2008may; 70(3):333-5.