1. SEMINAR ON
RATE- CONTROLLED DRUG
DELIVERY BY USING RATE-
PREPROGRAMMED DRUG
DELIVERY SYSTEMS
PRESENTED BY:
GANDHI SONAM MUKESHCHANDRA

2. INTRODUCTION
 Conventional drug delivery systems (DDS)
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3. Sustained release and controlled release DDS
70
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 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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6. 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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7.  Release of drug is controlled by controlling the partition
coefficient and diffusivity of the drug molecule and the
thickness of the rate-controlling membrane
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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8. PROGESTASERT
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9. OCUSERT SYSTEM
 thin disk of pilocarpine alginate complex sandwiched
between two transparent sheets of microporous ethylene-
vinyl acetate copolymer membrane.
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10.  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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11. B. POLYMER MATRIX DIFFUSION-CONTROLLED DDS
 Reservoir is prepared by homogenously dispersing drug particles in
a rate-controlling polymer matrix.
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12.  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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13. NITRO-DUR
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14. 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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15.  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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16. 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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17. 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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18. 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 18

19. Vasopressin
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20. 2. Hydrodynamic pressure activated DDS
 hydrodynamic pressure is used as the source of energy to activate
the drug release.
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21. 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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22. 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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23. 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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24. 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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25. 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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26. 26

27. 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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28.  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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29. Sonophoresis-activated drug delivery systems
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30. 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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31.  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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32. 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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33.  release of the drug is controlled by matrix diffusion through this
gel barrier
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34. REFERENCES
 NOVEL DRUG DELIVERY SYSTEMS, 2nd edition,Yie W. Chien
 CONTROLLED DRUG DELIVERY- FUNDAMENTALS AND
APPLICATIONS, 2nd edition, edited by Joseph R. Robinson and
Vincent H. L. Lee
 http://www.rxlist.com/ionsys-drug.htm
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35. THANK YOU
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