these are the drug delivery systems which are given orally and the drug release is such that it releases at a controlled way at a predetermined rate for a particular period of time.

1. ORAL CONTROL DRUG
DELIVERY SYSTEMS
SIVASWAROOP YARASI

2. Introduction:
• The primary objective of controlled drug
delivery is to ensure safety and improve
efficacy of drug as well as patients compliance
through better control of plasma drug level
and less frequent dosing.
• “An ideal controlled drug delivery system is
the one which delivers thr drug at a
predetermined rate, locally or systemically,
specific period of time”

3. Oral
controlled
DDS:
• The controlled release system for the oral use
are mostly solids and based on diffusion,
dissolution or a combination of both
mechanisms in the control of release rate of
drug.
• The goal is to achieve better therapeutic
success compared to conventional dosage
form of same drug.
• This could be achieved by improving
pharmacokinetics profile, patient compliance
and convenience in therapy.

4. Advantages:
• Improved patient compliance: improved
patient compliance is due to, reduced
frequency of administration.
• Reduced side effects due to low dose.
• Less fluctuating plasma drug level
• Better stability of drug.
• Reduction in drug accumulation with chronic
therapy
• Reduction in drug toxicity (local/systemic).
• Improvement in bioavailability of some drugs
because of spatial control.

5. Classification/approaches:
Dissolution controlled release.
Diffusion controlled release.
Ion exchange resins.
pH independent systems.
Osmolarity controlled release.
Altered density formulation / buoyant systems.

6. Dissolution
controlled
release:
• Easiest to design.
• Drug with slow dissolution rate is inherently
sustained
• E.g. griseofulvin, digoxin, and salycilamide act as
natural prolonged release products.
• Others aluminium aspirin, ferrous sulphate and
benzamphetamine produce slow dissolving from
when it comes to contact with GI fluids.
• Basic principle:
• If the dissolution process is diffusion layer
controlled where the rate of diffusion solid
sureface through a unstirred liquid film to
bulk solution is rate limiting the flux is ‘j’ is
given by

7. J=-D(dc/dx)
• Where,
• D= Diffusion coefficient.
• dc/dx = concentration gradient between the solid surface and bulk of
solution.

8. Types of dissolution controlled
release products:
Encapsulation/ coating dissolution controlled
system (reservoir devices)
Individual particles or
granules of drug.
Coated with slowly
dissolving materials like
cellulose, PEGs, waxes etc.
Coated granules are
compressed into tablets or
filled on capsules
The drug release is
controlled by dissolution
rate of polymeric coat.

9. Matrix (or monolith)/ embedded dissolution
controlled system.
• Drug is homogeneously dispersed throughout a
rate controlling medium matrix system.
• Waxes are used beeswax, carnauba wax,
hydrogenated castor oil etc.
Drug dispersed in molten wax
Congealing and granulating
The wax control the dissolution rate by
controlling the rate of dissolution fluid
penetration into matrix by latering the
porosity of tablet, decreasing its wettability.

10. Diffusion
controlled
release
system:
• Rate controlling step is diffusion of dissolved
drug through a polymeric barrier.
• Broadly classified into
• Reservoir type
• Matrix type

11. Reservoir type (or laminated
matrix devices):
• Drug is surrounded by a water insoluble
polymer membrane.
• Coating or microencapsulation are used to
apply polymer.
• Polymers like HPC, EC and polyvinyl acetate
are used commonly.
• Mechanism: drug partitioning into membrane
with subsequent release into the surrounding
fluid by diffusion.

12. • The rate of drug release explained by Ficks law of diffusion.
• Dm/dt = DSK(AC)/L
• S= active surface area.
• D= diffusion coefficient of the drug across the coating membrane.
• L = diffusional path length (thickness of polymer coat).
• AC = concentration difference across L.
• K= partition coefficient of drug between polymer and external medium.

13. Matrix diffusion controlled system:
• Drug is dispersed in insoluble matrix rigid
• non swellable hydrophobic materials
• PVC and fatty materials like stearic acid bees wax
etc
• or swellable hydrophilic substances like (glassy hydrogel)
• gums (Natural) – guar gum, tragacanth,
• Semi synthetic – HPMC, CMC xanthan gum.
• Synthetic – polyacrylamides.
• Mechanism: initial dehydration of hydrogel – swells –
drug diffuses out slowly.

14. Ion
exchange
resin:
• Ion exchange resins are cross-linked water-
insoluble polymers carrying ionizable
functional groups. These resins are used for
taste masking and controlled release system.
• The formulations are developed by
embedding the drug molecules in the ion-
exchange resin matrix and this core is then
coated with a semi permeable coating material
such as Ethyl Cellulose.
• This system reduced the degradation of drug
in GIT. The most widely used and safe ion-
exchange resin is divinylbenzene
sulphonate. In tablet formulations ion-
exchange resins have been used as
disintegrant.

15. Ion activated drug delivery system:
• An ionic drug can be delivered by ion activated drug delivery system.
• In electrolyte medium, such as gastric fluid, ions diffuse into system, react with drug resin
complex and triggers the release of ionic drug.
• Drugs suitable for resinate preparations:
• Should have acidic or basic groups.
• Half-life – 2 to 6 hrs.
• Should be absorbed from all regions of GIT
• Drug should be sufficiently in the gastric juice.

17. Osmotic
controlled
drug
delivery
system:
• Osmosis is defined as the movement of
solvent from lower to higher concentration
through semi permeable membrane.
• Osmotic pressure is the hydrostatic pressure
produced by a solution in a space divided by a
semi permeable membrane due to difference
in concentration of solutes.
• Principle:
• Osmotic pressure is the driving force that
generates constant drug release. In this system the
drug reservoir can be solution or solid formulation
and is placed in within the semi permeable
membrane housing with controlled water
permeability.

18. • The drug is activated to release in the solution form at a constant rate through a special delivery
orifice.
• Release of drug is activated by osmotic pressure and controlled at a rate determined by water
permeability, effective surface area of semi permeable housing and osmotic pressure gradient.
• The volume flow of water into core reservoir dv/dt is expressed as:
dv/dt = K A/ h (Δπ-Δp)
• K, A & h= Membrane permeability, effective surface, area & thickness of semi
permeable membrane, Δπ= osmotic pressure difference, Δp= hydrostatic pressure
difference.

19. Basic
components
of osmotic
pumps:
• Short half life
• Highly potent
• required for prolonged treatment.
Drug
• Inroganic water soluble agents:
• Magnesium sulfate, NaCl, KCl, NaHCO3 etc
• Organic polymer osmogents:
• Sod CMC, HPMC,HEMC, MC, PVP.
Osmotic agent: (osmogents)
• Must posses sufficient wet strength and wet modulus to
retain dimensional integrity.
• Sufficient water permeability so as ot retain water flux rate in
the desired range.
• Biocompatible.
Semi permeable membrane:

20. Oral osmotic pumps:
• Types:
• Single chamber:
• Elementary osmotic pump
• Multiple chamber:
• Push pull osmotic pump
• Osmotic pump with non expanding second chamber
• Specific osmotic pumps:
• Controlled porosity osmotic pumps.
• Monolithic osmotic pumps.
• Osmotic bursting osmotic pumps.

21. pH
independent
systems:
• Most drugs are either weak acids or weak bases.
• The release from controlled release formulation is pH
dependent.
• However buffers such as salts of amino acids, citric
acid, phthalic acid phosphoric acid or tartaric acid can
be added to formulation to maintain a constant pH
thereby rendering pH independent drug release.
• A buffered formulation is prepared by mixing a basic
or acidic drug with appropriate pharmaceutical
excipient and coating with GI fluid permeable film
forming polymer.
• When GI fluid permeates through the membrane, the
buffering agents adjust the fluid inside to suitable
constant pH thereby rendering a constant rate of drug
release.

22. Altered
density
system:
• These are also called floating systems or hydrodynamically
controlled systems.
• These are low density systems that have sufficient buoyancy to
float over the gastric contents and remain buoyant in the
stomach without affecting the gastric emptying rate for
prolonged period of time.
• While the system is floating the drug is released slowly at desired
rate.
• Selection of drug candidate:
• Drug must be absorbed from the upper part of GIT.
• Drugs that are acting locally in stomach.
• Drugs that are poorly soluble at alkaline pH.
• Drugs that degrade in the colon.

23. • Types:
• Effervescent system
• Non effervescent system

24. High density approach:
• in this density of pellets must exceed that of normal stomach content and
should therefore be at least 1.4g/cm3 .
• In preparing such formulations, drugs can be coated on heavy core or mixed
with heavy inert materials such as barium sulphate, titanium dioxide, iron
powder and zinc oxide. The weighted pellets can be covered with a
diffusional controlled membrane.