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1. Controlled Release Oral
Drug Delivery System

2. Contents
 Overview of Digestive system
 Introduction
 Advantages
 Disadvantages
 Mechanisms
1.Dissolution
2.Diffusion
3.Combination of Dissolution & Diffusion
4.Osmotic pressure controlled system
 References
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3. Digestive System
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4. Concept
 Controlled drug delivery is one which
delivers the drug at a predetermined rate,
for locally or systemically, for a specified
period of time.
 Continuous oral delivery of drugs at
predictable & reproducible kinetics for
predetermined period throughout the
course of GIT.
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5. Plasma concentration time profile
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6. Challenges in Oral Drug
Delivery
 Development of drug delivery system
Delivering a drug at therapeutically effective rate to
desirable site.
 Modulation of GI transit time
Transportation of drug to target site.
 Minimization of first pass elimination
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7. Advantages
 Total dose is low.
 Reduced GI side effects.
 Reduced dosing frequency.
 Better patient acceptance and compliance.
 Less fluctuation at plasma drug levels.
 More uniform drug effect
 Improved efficacy/safety ratio.
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8. Disadvantages
 Dose dumping.
 Reduced potential for accurate dose adjustment.
 Need of additional patient education.
 Stability problem.
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9. Mechanism aspects of Oral drug
delivery formulation
1.Dissolution : 1.Matrix
2.Encapsulation
2.Diffusion : 1.Matrix
2.Reservoir
3.Combination of both dissolution & diffusion.
4.Osmotic pressure controlled system
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10. Dissolution Definition:
 Solid substances solubilizes in a given
solvent.
 Mass transfer from solid to liquid.
 Rate determining step: Diffusion from solid
to liquid.
 Several theories to explain dissolution –
Diffusion layer theory (imp)
Surface renewal theory
Limited solvation theory.
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11. Noyes Whitney Equation
dc/dt = kD.A (Cs – C )
dc/dt = D/h A. (Cs – C)
dc/dt = Dissolution rate.
k= Dissolution rate constant (1st order).
D = Diffusion coefficient/diffusivity
Cs = Saturation/ maximum drug solubility.
C =Con. Of drug in bulk solution.
Cs-C=concentration gradient.
h =Thickness of diffusion layer.
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12. Matrix Type
 Also called as Monolith dissolution
controlled system. Soluble drug
 Controlled dissolution by:
1.Altering porosity of tablet.
2.Decreasing its wettebility.
3.Dissolving at slower rate.
Slowly
 First order drug release. dissolving
matrix
 Drug release determined by dissolution
rate of polymer.
 Examples: Dimetane extencaps,
Dimetapp extentabs.
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13. Encapsulation
 Called as Coating dissolution
controlled system.
 Dissolution rate of coat depends Soluble drug
upon stability & thickness of coating.
 Masks colour,odour,taste,minimising
GI irritation. Slowly
dissolving
 One of the microencapsulation or erodible
method is used. coat
 Examples: Ornade spansules,
Chlortrimeton Repetabs
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14. Diffusion
 Major process for absorption.
 No energy required.
 Drug molecules diffuse from a region of higher concentration to
lower concentration until equilibrium is attainded.
 Directly proportional to the concentration gradient across the
membrane.
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15. Matrix Diffusion Types
 Rigid Matrix Diffusion
Materials used are insoluble plastics such as PVP & fatty
acids.
 Swellable Matrix Diffusion
1. Also called as Glassy hydrogels.Popular for sustaining
the release of highly water soluble drugs.
2. Materials used are hydrophilic gums.
Examples : Natural- Guar gum,Tragacanth.
Semisynthetic -HPMC,CMC,Xanthum gum.
Synthetic -Polyacrilamides.
Examples: Glucotrol XL, Procardia XL
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16. Matrix system
Rate controlling
step:
Diffusion of dissolved
drug in matrix.
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17. Higuchi Equation
Q = DE/T (2A.E Cs)Cs.t)1/2
Where ,
Q=amt of drug release per unit surface area at time t.
D=diffusion coefficient of drug in the release medium.
E=porosity of matrix.
Cs=solubility of drug in release medium.
T=tortuosity of matrix.
A=concentration of drug present in matrix per unit
volume.
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18. Reservoir System
 Also called as Laminated matrix device.
 Hollow system containing an inner core
surrounded in water insoluble membrane.
 Polymer can be applied by coating or micro
encapsulation.
 Rate controlling mechanism - partitioning into
membrane with subsequent release into
surrounding fluid by diffusion.
 Commonly used polymers - HPC, ethyl cellulose
& polyvinyl acetate.
 Examples: Nico-400, Nitro-Bid
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19. Reservoir System
Rate controlling
steps :
Polymeric content in
coating, thickness of
coating, hardness of
microcapsule.
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20. Dissolution & Diffusion
Controlled Release system
 Drug encased in a partially soluble
membrane.
 Pores are created due to dissolution Insoluble
membrane
of parts of membrane.
Entry of
 It permits entry of aqueous medium
dissolution
into core & drug dissolution. fluid
 Diffusion of dissolved drug out of Drug
system. diffusion
 Ex- Ethyl cellulose & PVP mixture
Pore created by
dissolves in water & create pores of dissolution of
insoluble ethyl cellulose membrane.
soluble fraction of
membrane
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21. Osmotic Pressure Controlled
Drug Delivery System
 Definition
 Procedure
 Diagram
 Modifications
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22. Osmosis
- Movement of solvent from lower to higher concentration.
 - The passage of solvent into a solution through
semipermeable membrane.
Semipermeable Membrane
 Molecules are permitted only to one component (Water).
Osmotic pressure
 It is the hydrostatic pressure produced by a solution in a space
divided by a semipermeable membrane due to difference in
concentration of solutes.
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23. Osmotic Pressure Controlled
System
 Provides zero order release
 Drug may be osmotically active, or combined with an
osmotically active salt (e.g., NaCl).
 Semipermeable membrane usually made from cellulose
acetate.
 More suitable for hydrophilic drug.
 Examples: Glucotrol XL, Procardia XL,
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24. Equation
(Q/t) z = Pw Am/ hm (πs-πe )
(Q/t)= Rate of zero order drug release.
Pw, Am & hm= water permeability, effective surface
area & thickness of semipermeable membrane.
πs= osmotic pressure of saturated solution of
osmotically active drug or salt in system.
πe = osmotic pressure of GI fluid.
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25. Osmotic Pressure Controlled System
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26. Osmotic Pressure Controlled System
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27. Modifications
- Immediate release system.
- Osmotically active compartment system

28. Immediate Release System
 Activation of system is done.
 Dividing a dose into two parts.
 One third immediate release.
 Two third controlled release.
 Encapsulated into semipermeable
membrane.
e.g. : Phenyl propanolamine.
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29. Osmotically active system
 Two compartments Delivery orifice
separated by movable
partition.
 Osmotically active Drug compartment
compartment absorbs Movable
partition
water from GIT. Osmotically active
 Creates osmotic compartment
pressure.
 Partition moves upward
& then drug releases.
 Ex: Nifedipine.
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30. Some Popular Brand names used
for OCDDS
 Spansule capsule ( SK & F )
 Sequal capsule (Lederle )
 Extentab tablets ( Robins )
 Timespan tablet ( Roche )
 Dospan tablet ( Merrell Dow )
 Chronotab tablet ( Schering )
 Plateau capsule ( Marion )
 Tempule capsule ( Armour )
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31. Some Examples of OCDDS
 Propranolol (Inderal LA)
 Methyiphenidate HCl (RitalinSR)
 Iron (Slow-Fe)
 GITS-Prazosin (Minipress)
 Morphine sulfate (Roxanol SR)
 Decongestant & antihistamine (Resaid SR, Novafed SR
Dristan)
 Pseudoephedrine HCI (Sudafed SA)
 Potassium (Micro-K, Slow-K, Klotrix)
 Antitussive combinations (Rescap, Ornade Spansules)
 Chlorpheniramine maleate (ChlorTrimeton)
 Decongestant, antihistamine and anticholinergic (Dallergy,
Supres)
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32. Recent Trends : Extended release
formulation of Bupropion
 Bupropion is used in the treatment of major depressive
disorder.
 Conventional formulation has to be administered 3 times
daily
 Initially 150 mg ER formulation was introduced for bid
regimen
Later on 300 mg ER formulation was introduced for once
daily regimen
 For ER formulation provide similar Cmax and AUC values
as compared to immediate release formulation at steady
state.
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33. Recent Trends : Extended release
formulation of Bupropion
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34. Recent Trends: OROS Technology
(ALZA corporation)
ELEMENTARY OSMOTIC PUMP
 Single layer tablet: Drug
core (water soluble drug
with or without excipients)
 Semipermeable membrane
with a drilled orifice
 Water imbibition by the core
because of osmotic action
results in drug dissolution,
which is released at a
controlled rate through the
orifice
 Not suitable for water insoluble drugs.
 Examples: Sudafed 24
hours (Pseudoephedrine); Volmax (Salbutamol)
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35. Recent trends: Geomatrix® (SKY Parma)
Products in market:
Cordicant -uno®
Madopar DR
SULAR ER
This technology Controls amount,
timing and location of release in body.
-Formulation with predictable and
reproducible drug release profile.
-Controls rate of drug diffusion
throughout release process,
ensuring 100% release Products
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36. References
 Novel drug delivery system , volume 50,
Y.W.Chien
 The theory & practice of industrial pharmacy,
Leon Lachman , Herbert A.Lieberman,
Joseph L.Kanig,3 rd edition.
 The Eastern pharmacist, november 1993.
Sustained release drugs, V R.Gudsoorkar & D.Rambhau
page 27-32
 Biopharmaceuitics & pharmacokinetics,
D M.Brahmankar & Sunil B. Jaiswal.
www.google.com
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37. Thank you for listening me………
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