2. INTRODUCTION
 Conventional drug delivery systems (DDS)
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3. Sustained release and controlled release DDS
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60
50
40
Solution
Dexatrim
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Acutrim
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10
0
0 5 10 15 20 25 30
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4. CLASSIFICATION
 Rate- preprogrammed drug delivery systems
 Activation – modulated drug delivery systems
 Feedback- regulated drug delivery systems
 Site- targeting drug delivery systems
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5. Rate- Preprogrammed
drug delivery systems
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6. RATE- PREPROGRAMMED DDS
 Release of drug molecules from the delivery systems has
been preprogrammed at specific rate profiles
 Diffusion of drug molecules into the medium is
controlled
CLASSIFICATION OF RATE- PREPROGRAMMED DDS
A. Polymer membrane permeation-controlled drug
delivery systems
B. Polymer matrix diffusion-controlled drug delivery systems
C. Micro reservoir partition-controlled drug delivery systems
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7. A. POLYMER MEMBRANE PERMEATION-CONTROLLED
DDS
 Drug release surface of the reservoir compartment
is rate-controlling polymeric membrane.
 Polymeric membrane can be
nonporous, microporous or semi permeable in
nature.
 Encapsulation of drug in the reservoir is
accomplished by injection molding, spray
coating, capsulation or microencapsulation.
 Q/t = [(Km/r Ka/m Dd Dm)/( Km/r Dm hd + Ka/m Dd hm)]
cR
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8.  Release of drug is controlled by controlling the
partition coefficient and diffusivity of the drug
molecule and the thickness of the rate-controlling
membrane
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9. EXAMPLES:
PROGESTASERT IUD:
reservoir - suspension of progesterone crystals in silicone
medical fluid
Membrane- nonporous membrane of ethylene vinyl acetate
copolymer
Deliver natural progesterone continuously in the uterine
cavity at a daily dosage rate of at least 65 µg/day to
achieve contraception for1 year.
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10. PROGESTASERT
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11. OCUSERT SYSTEM
 thin disk of pilocarpine alginate complex
sandwiched between two transparent sheets of
microporous ethylene-vinyl acetate copolymer
membrane.
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12.  Either 20 or 40 µg/hr of pilocarpine is released
TRANSDERM-NITRO
 Nitroglycerin-lactose triturate in the silicone
medical fluid
 Micro porous membrane of ethylene-vinyl acetate
copolymer
 Thin layer of pressure-sensitive silicone adhesive
polymer is coated
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13. B. POLYMER MATRIX DIFFUSION-CONTROLLED DDS
 Reservoir is prepared by homogenously dispersing drug
particles in a rate-controlling polymer matrix.
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14.  Q/t1/2 = (2ACRDp)1/2
 release of drug is controlled by controlling the
loading dose, polymer solubility of the drug, and
its diffusivity in the polymer matrix
EXAMPLES
NITRO-DUR
 Nitro-glycerine transdermal patch
 for 24 hr to provide a continuous transdermal
infusion of nitro-glycerine at a dosage rate of 0.5
mg/cm2/day for the treatment of angina pectoris.
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15. NITRO-DUR
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16. C. MICRORESERVOIR PARTITION- CONTROLLED DRUG
DELIVERY SYSTEMS
 Micro dispersion of an aqueous suspension of drug using
a high-energy dispersion technique in a bio-compatible
polymer,(Eg. silicone elastomers), forms a homogenous
dispersion of many discrete, unleachable, microscopic
drug reservoirs.
 device can be further coated with a layer of
biocompatible polymer to modify the mechanism and
the rate of drug release
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17.  Release of drug molecules from this type of
CRDDS can follow either dissolution or a matrix
diffusion-controlled process depending upon the
relative magnitude of Sl and Sp
EXAMPLES
NITRODISC SYSTEM
 Nitro-glycerine in silicone elastomer
 0.5mg/cm2 for once-a-day
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18. Activation – modulated
drug delivery systems
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19. ACTIVATION MODULATED DDS
 Drug delivery is activated and controlled by
physical, chemical or bio-chemical processes or
facilitated by the energy supplied externally
Classification of activation modulated DDS
 Based on the nature of the process applied or the type
of energy used
1. Physical means
2. Chemical means
3. Biological means
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20. DDS activated by physical means
a. Osmotic pressure- activated DDS
b. Hydrodynamic pressure activated DDS
c. Vapour pressure activated DDS
d. Mechanically activated DDS
e. Magnetically activated DDS
f. Sonophorosis activated DDS
g. Iontophoresis activated DDS
h. Hydration activated DDS
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21. 1. Osmotic pressure- activated DDS
 drug reservoir can be a solution contained within an
impermeable collapsable tube.
 This is covered with osmotic agent place in a rigid semi
permeable housing with controlled water permeability.
 The rate of drug release is modulated by the gradient of
osmotic pressure.
Q/t = PwAm (πs-πe) /hm
Pw = water permeability
Am = effective surface area
hm =thickness of the semi permeable housing
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22. 22

23. Vasopressin
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24. 2. Hydrodynamic pressure activated DDS
 hydrodynamic pressure is used as the source of energy
to activate the drug release.
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25. Q/t = Pf Am/hm (θs – θe)
Pf = fluid permeability
Am = effective surface area
hm = thickness of the wall with annular openings
θs – θe = difference in hydrodynamic pressure between the
DDS and the environment
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26. 3. Vapour pressure- activated drug delivery systems
 Drug inside infusion compartment is separated from
pumping compartment by freely movable partition.
 Pumping compartment contains a fluorocarbon
fluid that vaporizes at body temperature
 The vapour pressure created moves the partition
upward, forcing the drug to be delivered.
 Eg: INFUSAID implants (heparin)
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27. 1. Flow regulator, 2. silicone polymer coating, 3. patrition,
4. Pumping compartment, 5. Infusate compartment, 6.
fluorocarbon fluid filling tube, 7. filter assembly, 8. inlet
septum for percutaneous refill of infusate, 9. needle stop.
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28. Q/t= d4(Ps-P-e)/40.74µl
d & l = the inner diameter and the length of the delivery
cannula, respectively
Ps-P-e = difference between the vapour pressure in the
pumping compartment and the site of
implantation.
µ = viscosity of the drug formulation used.
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29. 4. Mechanically activated drug delivery system
 Equipped with a mechanically activated pumping system
 A measured dose of drug formulation is reproducibly
delivered
 The volume of solution delivered is controllable, as small as
10-100µl
 Volume of solution delivered is independent of the force &
duration of activation applied as well as the solution volume
in the container.
 Example is the development of metered dose nebulizer for
the intranasal administration of a precision dose of buserelin
(LHRH).
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30. 30

31. 5. Magnetically activated drug delivery systems
 Drug reservoir is a dispersion of peptide or protein
powders in a polymer matrix
 Low rate of delivery is improved by incorporating
electromagnetically triggered vibration mechanism
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32.  Coating polymer can be a ethylene-vinyl acetate
copolymer or silicon elastomers.
 These systems have been used to deliver protein
drugs, such as bovine serum albumin
6. Sonophoresis-activated drug delivery systems
 Utilize ultrasonic energy to activate the delivery of the
drugs from a polymeric drug delivery device
 can be fabricated from either a non degradable
polymer, such as ethylene-vinyl acetate copolymer,
a bio erodible polymer such as poly[bis(p-
carboxyphenoxy)alkane anhydride].
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33. Sonophoresis-activated drug delivery systems
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34. 7. Iontophoresis-activated drug delivery systems
 uses electrical current to activate and to modulate
the diffusion of a charged drug molecule across
the skin in a facilitated rate
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35.  skin permeation rate of a charged molecule i consist of 3
components
Jiisp = Jp+Je+Jc
Jp = passive skin permeation flux
Je = electrical current driven permeation flux
Jc = convection flow-driven skin permeation flux
 IONSYS - fentanyl iontophoretic transdermal system
 Example : development of an iontophoretic DDS of
dexamethasone sodium phosphate
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36. 8. Hydration-activated drug delivery system
 Depends on the hydration induced swelling process to
activate the release of drug
 Drug reservoir is homogeneously dispersed in a swellable
polymer matrix fabricated from a hydrophilic polymer
 Release of the drug is controlled by the rate of swelling of
the polymer matrix.
 Example is VALRELEASE tablet- diazepam in hydrocolloid
and pharmaceutical excipients.
 In stomach absorbs the gastric fluid & forms colloidal gel
that starts from the tablet surface and grows inward.
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37.  release of the drug is controlled by matrix diffusion
through this gel barrier
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39.  In this group of controlled-release drug
delivery systems the release of drug molecules
from the delivery systems is activated by a
triggering agent, such as a biochemical
substance, in the body and also regulated by
its concentration via some feedback
mechanisms.
 The rate of drug release is then controlled by
the concentration of triggering agent
detected by a sensor in the feedback-
regulated mechanism.

40.  There are 3 different sub-type of this system :
 Bioerosion Regulated Drug Delivery
System
 Bioresponsive Drug Delivery System
 Self-Regulating Drug Delivery System

41.  Thefeedback regulated drug delivery
concept was applied to the
development of a Bioerosion-
regulated drug delivery system by
Heller and Trescony.

42.  The system consists of drug-dispersed
bioerodible matrix fabricated from poly(vinyl
methyl ether) half-ester, which was coated
with a layer of immobilized urease.
 In a solution with near neutral pH, the polymer
only erodes very slowly.

43.  In the presence of urea, urease at the surface
of drug delivery system metabolizes urea to
form ammonia.
 This causes the pH to increase and a rapid
degradation of polymer matrix as well as the
release of drug molecules.

45.  In this system the drug reservoir is
contained in a device enclosed by a
Bioresponsive polymeric membrane whose
drug permeability is controlled by a
concentration of a biochemical agent in
a tissue where the system is located.

46.  A typical example of this Bioresponsive
drug delivery system is the development of
a glucose-triggered insulin delivery system
in which the insulin reservoir is
encapsulated in within a hydrogel
membrane having pedant –NR2 groups.
 In alkaline solution the –NR2 groups are
neutral and the membrane is unswollen
and impermeable to insulin.

47.  As glucose, a triggering agent, penetrates into
the membrane, is oxidized enzymatically by the
glucose oxidase entrapped in the membrane
to form gluconic acid.
 The –NR2 groups are protonated to form –
NR2H+ and hydrogel membrane then become
swollen and permeable to insulin molecules.
 The amount of insulin delivered is thus
Bioresponsive to the concentration of glucose
penetrating the insulin delivery system.

49. Self-Regulating Drug
Delivery System
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50.  This type of feedback-regulated drug delivery
system depends on a reversible and competitive
binding mechanism to activate and to regulate
the release of drug.
 In this system the drug reservoir is a drug complex
encapsulated within a semipermeable polymeric
membrane.
 The release of drug from the delivery system is
activated by the membrane permeation of
biochemical agent from the tissue in which the
system is located.

51.  Kim et al. first applied the mechanism of
reversible binding of sugar molecules by lectin
into the design of self-regulating drug delivery
system.
 It first involves the preparation of biologically
active insulin derivatives in which insulin is
coupled with a sugar and this into a insulin-
sugar-lectin complex.
 The complex is then encapsulated within a
semipermeable membrane.

52.  As blood glucose diffuses into the device and
competitively binds at the sugar binding sites
in lectin molecules, this activates the release
of bound sugar-insulin derivatives.
 The released insulin-sugar derivatives then
diffuse out of the device, and the amount of
insulin-sugar derivatives released depends on
the glucose concentration.
 Thus a self regulating drug delivery is
achieved.

53.  However the potential problem exists: that
is, the release of insulin is non-linear in
response to the changes in glucose level.
 Further development of the self-regulating
insulin delivery system utilized the complex
of glycosylated insulin-concavalin
A, which is encapsulated inside a polymer
membrane.

54.  As glucose, the triggering agent, penetrates
the system, it activates the release of
glycosylated insulin from the complex for the
controlled delivery out of the system.
 The amount of insulin delivered is thus self-
regulated by the concentration of glucose
penetrating the insulin delivery system.

56. THANK YOU