1. Controlled Release Oral Drug Delivery System
K.vidya Sagar
B.pharmacy
Dr.Samuel George Institute Of pharmaceutical Sciences
Acharaya nagarjuna university, Markapu ,Andhrapradesh, India
Cell No:

2. Nepal Pharmaceutical Ltd., Nepal
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. Nepal Pharmaceutical Ltd., Nepal
Digestive System
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4. Nepal Pharmaceutical Ltd., Nepal
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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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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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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Nepal Pharmaceutical Ltd., Nepal

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. Nepal Pharmaceutical Ltd., Nepal
Matrix Type
Also called as Monolith dissolution controlled system.
Controlled dissolution by:
1.Altering porosity of tablet.
2.Decreasing its wettebility.
3.Dissolving at slower rate.
First order drug release.
Drug release determined by dissolution rate of polymer.
Examples: Dimetane extencaps, Dimetapp extentabs.
Soluble drug
Slowly dissolving matrix
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13. Nepal Pharmaceutical Ltd., Nepal
Encapsulation
Called as Coating dissolution controlled system.
Dissolution rate of coat depends upon stability & thickness of coating.
Masks colour,odour,taste,minimising GI irritation.
One of the microencapsulation method is used.
Examples: Ornade spansules, Chlortrimeton Repetabs
Soluble drug
Slowly dissolving or erodible coat
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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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Matrix system
Rate controlling step:
Diffusion of dissolved drug in matrix.
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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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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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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 of parts of membrane.
It permits entry of aqueous medium into core & drug dissolution.
Diffusion of dissolved drug out of system.
Ex- Ethyl cellulose & PVP mixture dissolves in water & create pores of insoluble ethyl cellulose membrane.
Insoluble membrane
Entry of dissolution fluid
Drug diffusion
Pore created by dissolution of soluble fraction of membrane
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21. Osmotic Pressure Controlled Drug Delivery System
Definition
Procedure
Diagram
Modifications
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22. Nepal Pharmaceutical Ltd., Nepal
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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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. - Immediate release system. - Osmotically active compartment system
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 separated by movable partition.
Osmotically active compartment absorbs water from GIT.
Creates osmotic pressure.
Partition moves upward & then drug releases.
Ex: Nifedipine.
Delivery orifice
Drug compartment
Movable partition
Osmotically active compartment
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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. Nepal Pharmaceutical Ltd., Nepal
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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Nepal Pharmaceutical Ltd., Nepal

33. Recent Trends : Extended release formulation of Bupropion
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Nepal Pharmaceutical Ltd., Nepal

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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Nepal Pharmaceutical Ltd., Nepal

36. Nepal Pharmaceutical Ltd., Nepal
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.
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37. Nepal Pharmaceutical Ltd., Nepal
Thank you for listening me………
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