This document discusses various types of controlled drug delivery systems including diffusion controlled, dissolution controlled, and combined controlled systems. It describes the mechanisms of drug release for different types such as matrix systems, membrane controlled devices, and osmotic pressure devices. Key factors affecting drug release from these systems are also summarized such as polymer properties, drug solubility, and membrane thickness. The advantages of controlled drug delivery systems in improving bioavailability and patient compliance are highlighted.

1. Various controlled drug delivery
systems
Diffusion controlled DDS
Dissolution controlled DDS
Combined controlled DDS
Prepared by :Ishita B
Ist M.Pharm
Department of Pharmaceutics
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2. Contents
• Definition
• Types
• Mechanism
• Advantages and Disadvantages
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3. Controlled Drug Delivery System
What do we mean by “controlled” release?
Control of
1. delivery rate
2. site of release/activity
But the drug release is continuous and
predictable across the git transit.
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4. Controlled versus conventional drug
delivery system
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5. Diffusion controlled drug delivery
system
Herein the drug is released by diffusion across matrix.
Diffusion is the rate limiting step.
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6. Types of diffusion controlled dds
Types of Diffusion Controlled Delivery Devices
• Monolithic Devices (matrix type)
• Membrane Controlled Devices
• Osmotic Pressure Devices
• Swelling-Controlled Devices
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7. Kinetic considerations of drug release
from diffusion controlled DDS
• First step in drug release is -
drug dissolution into surrounding medium.
• Second step -
the controlled release process
• Third step –
the interfacial partitioning of drug molecules
from polymer towards solution
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8. • Drug Partitioning depends on solubility in
solution Cs and in polymer Cp
K = Cs /Cp
• 4rth step-
The diffusion coefficient of a drug molecule in a
given medium is constant.
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9. i) Case of C0 < Cs
(drug concentration C0 is below solubility limit in
matrix Cs)
⇒ Diffusion through matrix limits the release rate.
How can we control release rate?
Rate control by choice of matrix:
• glassy matrix: D~10-10-10-12 cm2/s
• rubbery matrix: D ~ 10-6-10-7 cm2/s
Drug release governed by fick’s laws
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10. Monolithic /matrix drug delivery
Devices
Drug /therapeutic agent is dispersed in polymer matrix and
released by diffusion out of matrix .Release rate depends on
initial drug concentration
To formulate such systems :-
Polymer+active agent mixed to form homogenous systems
Diffusion occurs when drug passes from polymer matrix into
external envmt .
With the passage of time and continuous drug release , the
delivery rate normally decreases in these type of systems
since the drug has to transverse long distances progressively
and thereby require a longer diffusion time for ultimate
delivery of drugs
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12. Matrix swelling process in diffusion
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13. Membrane Controlled Devices aka
Reservoir type DDS
Drug particles encapsulated by polymeric membrane of specific
‘dp’ thickness.
Thus drug release controlled by diffusion across semi-permeable
membrane.
It limits the release rate .
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14. • The drug molecules in the outermost layer of
particles firstly have to dissociate from the
crystal lattice before dissolving into and
subsequently diffusing through the polymer
structure and eventually leading to
partitioning into elution media.
• A hydrodynamic diffusion layer of δd thickness
is also present on surface of device
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Mechanism

15. Advantage:
A constant flux device
Types :
i) Nonporous semi-permeable membranes
⇒ Drug diffusion through swollen polymer
membrane
ii) Porous semi-permeable membranes
⇒ Drug diffusion through membrane pores
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16. Mathematical expression reservoir
type dds
• The cumulative amount of drug released from
unit surface area of reservoir type dds is
expressed as :-
Q = (CpKDsDp/KDsδp+Dpδd)t
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17. Reservoir type drug delivery systems
• This eqn suggests that drug molecules release
under diffusion layer limiting partition-
controlled process
• And drug release rate is linearly proportional
to product of solution conc and soln difusivity
Ds and is inversely proportional to thickness of
hydrodynamic diffusion layer
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18. 6/5/2016 18

19. Comparison between membrane versus
matrix
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20. Osmotic Pressure Devices
• Such devices depends on osmotic pressure to
activate drug release.
• In this the drug reservoir can be either a solution
or a solid formulation within a SPM with
controlled water permeability.
• The drug is activated to release in solution form
at a constant rate through a special delivery
orifice .
• The rate of drug release is modulated by
controlling the gradient of osmotic pressure .
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Osmotic pressure build-up from water in-flux
across semi-permeable membrane forces
drug release through orifice
Release rate proportional to change in volume
of drug reservoir .
Factors affecting drug release are:
Osmotic pressure
Water permeability
Effective surface area of the SPM
E.g. of osmotic pressure cdds is :-
Implantable /insertable alzet osmotic pump

22. Implantable /insertable ALZET osmotic
pump
• In this the drug is usually in the form of solution
formulation, present in collapsible impermeable
polyester bag whose external surface is coated
with layer of osmotically active salt such as
sodium chloride. This entire setup is placed inside
a spm
• At the implantation site, the water component in
the tissue fluid penetrates through the spm at a
specific rate to dissolve the osmotically active
salt.
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• This creates an osmotic pressure ‘π’ in the
narrow space between flexible non-spm drug
reservoir and the rigid spm surrounding the
drug formulation.
• Under the pressure difference‘π’ the drug
compartment is forced to reduce its volume
and the drug is released at controlled rate
through the flow modulator in the system.
• By varying the drug concentration in the
solution different doses of drug can be
delivered at constant rate for a period of 1-4
weeks.

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25. Mechanism : osmosis
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26. Two types of osmotically controlled
devices
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27. Acutrim tablet
• An oral rate controlled drug delivery device
• A solid tablet of water soluble and osmotically active
phenylpropanolamine (PPA) HCl enclosed within a spm
made from cellulose triacetate.
• The surface of spm is further coated with thin layer of
PPA dose for immediate release
In git the git fluid dissolves the immediately releasable
PPA layer which provides an initial dose of PPA and its
water component then penetrates through the spm at
a predetermined rate to dissolve the dose of PPA.
PPA is released at a predetermined rate due to pressure
difference between device spm and body fluids.
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29. Swelling Controlled Devices
The physical phenomena, which can be involved
in the control of drug release from swellable
delivery systems, namely, water diffusion,
polymer chain relaxation, drug dissolution and
diffusion, as well as polymer dissolution. It is
mass transport processes .
It involves swelling devices .
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30. Swelling agents
• Are hydrophilic crosslinked polymers, which swell
from 10 to 1,000 times their own weight when
placed in an aqueous medium.
• Depending on their swelling properties, these
materials have been exploited in developing
three different classes of materials in
pharmaceutical industries, i.e. swellable
matrices, superdisintegrants and swelling devices.
• Since their development, these pharmaceutical
excipients have found significant applications in
drug delivery area
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Hydrogels have been used in controlled-release
DDS
Reason: good tissue compatibility and
easy manipulation of swelling level and,
thereby, solute permeability.
The desired kinetics, duration, and rate of
solute release from hydrogels are limited to
specific conditions, such as hydrogel
properties, amount of incorporated drug, drug
solubility, and drug-polymer interactions.

33. Factors affecting diffusion controlled
dds
• Partition coefficient K of drug is defined as
partitioning of drug from the surface of dds
towards the elution system that is body fluid
/blood
K = CS
/ CP
CS =
solubility of drug in elution medium
CP =
solubility of drug in polymer
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34. Polymer Diffusivity
• Diffusion of drug across the polymer depending
on the strength of intramolecular bonding in
polymer chain
• This is further dependent on cross linking within
the polymer chains
• What happens is due to increase in cross linking
,reduced mobility +decreased porosity of
polymer chain ; increased tortuousity for
diffusion of drug molecules in polymer structure.
• decreased porosity+increased tortuousity causes
reduced diffusion of drug across polymer
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35. Polymer Membrane Thickness
• Diffusivity path thickness i.e. : thickness of
polymer membrane
• More the membrane thickness lesser the
diffusion
• Therefore the drug should be enclosed in thin
polymer membrane to maximize diffusion.
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36. Polymer crystallinity
• Low density polyethylene has lower degree of
crystallinity than high density polyethylene
• Crystallinity introduces regions of very low
diffusivity for diffusion in surrounding regions
as compared to amorphous structure.
• Thus , diffusion decreases as crystallinity
increases.
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37. Effect of fillers
• Fillers are incorporated to polymers to
enhance its mechanical strength .however
they reduce drug diffusion.
• E.g. :-Pure and finely ground silica particles
was added to silicone elastomers to improve
mechanical strength
• This leads to decreased diffusion because of
Langmuir adsorption of diffusant molecules
onto the active filler.
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38. Dissolution controlled drug delivery
system
Dissolution-controlled drug delivery systems are
characterized by a phase erosion of the
polymer carrier that is associated with fast or
slow dissolution of the macromolecular
chains.
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39. Mechanism of dissolution controlled
• Sustain release oral products employing
dissolution as the rate limiting step is the
principle involved in this system
• To achieve this type of approach the drug
particles can be coated with material of
varying thickness or by dispersing them in
polymeric matrix.
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40. Types of dissolution controlled dds
• Encapsulation dissolution control :
Herein coating of particles /granules of a drug
with slow dissolving material
• Matrix dissolution control
In this a solid drug is dispersed in insoluble
matrix
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41. Dissolution controlled drug
release system
Types
Explanation
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42. a. Encapsulation type
• Also called as Coating dissolution controlled
system,
• Since the individual particles of drug
encapsulated, with slowly dissolving material like
cellulose, PEG, PMA (poly methylacrylates)&
waxes.
• Dissolution rate of coat depends upon stability ie
aq solubility &thickness of coating
• Coated particles can be compressed directly as
tablets (spacetabs) or placed in capsules
(spansules)
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43. b. Matrix type aka Monolithic dissolution
controlled system
Since the drug homogenously dispersed throughout a
rate controlling medium waxes (beeswax, carnauba wax,
hydrogenated castor oil etc) which control drug
dissolution by controlling the rate of dissolution
1. Altering porosity of tablet.
2. Decreasing its wettability.
3. Dissolving at slower rate.
• Exhibit First order drug release.
• Drug release determined by dissolution rate
of polymer.
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44. Dissolution controlled dds comparison
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45. Noye’s whiteney equation
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46. Dissolution : principle
Noye’s Whitney equation
• Dm/dt= mass rate of dissolution (mass of drug
dissolved per unit time )mg/min
• D =diffusion coefficient of solute in solution cm2/s
• S=surface area of exposed solid cm2
• k= dissolution rate constant cm/s
• h= thickness of unstirred layer at solid surface cm
• Cs= drug solubility at particle surface g/ml
• C=drug concentration in bulk solution g/ml
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47. Factors affecting dissolution
• Drug solubility : more drug soluble , more
dissolution
• Viscosity of dissolving medium: more viscous
solution less dissolution
• Diffusion layer thickness : more the thickness,
more dissolution
• Ph of dissolving medium :drug dissolution
depends on nature of drug and ph of stomach
/intestine. Acidic drugs solubilise easily in basic
ph and vice versa
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• Particle size : less particle size ,more dissolution
• Surface area : more surface area, more
dissolution
• Crystallinity of drug : less crystalline drug more
dissolution because easier for unorganized
lattices of drug/polymer to enter into solution.
Also because weak attraction forces in
amorphous form compared to amorphous forms
• Porosity of drug : more porous drug ,better
dissolution
• Temperature : higher temperature increases rate
of dissolution but lower temperature retards
because of decrease in kinetic energy thus
vibrations of molecules

49. Combined controlled drug delivery
system i.e. 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
Ethyl cellulose & PVP mixture dissolves in water &
create pores of insoluble ethyl cellulose membrane
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50. Mechanism of dissolution controlled dds
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52. Comparison between diffusion and
dissolution controlled drug delivery
Diffusion controlled dds
• Mechanism- diffusion
• Maybe:-
Monolithic Devices
Membrane Controlled Devices
Osmotic Pressure Devices
Swelling-Controlled Devices
Guided by fick’s law
• Factors affecting : governed
by polymer matrix and drug
solubility
Dissolution controlled dds
• Mechanism -dissolution
• Maybe :-
Encapsulation dissolution control :
drug coated with slow dissolving material
Matrix dissolution control
drug dispersed in insoluble matrix
• Guided by noye’s –Whitney
equation
• Factors affecting : governed
by polymer matrix and drug
solubility and others
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53. Advantages of CDDS
Improved bioavailability
• Improved patient compliance
• Reduction in dosing
• Wide variety of drugs can be formulated
• Reason to formulate cdds :-
to overcome the drawback of fluctuatig drug levels
associated with conventional dosage forms
• Controlled delivery at predetermined rate
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54. Disadvantages of CDDS
• Highly expensive
• Often poor in vivo invitro correlation
• Dose dumping
• Poor systemic availability
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