Types of oral controll drug delivery system

1. TYPES OF ORAL CONTROL DRUG
DELIVERY SYSTEMS
Presented by;
K. Sai Lakshmi
B-Pharmacy, final year,
(2016-2020)
Balaji College of Pharmacy.

2.  Orally controlled release drug delivery systems are
employed to obtain controlled and sustained drug
effect.
 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.

3. 1.Diffusion controlled Release system
2.Dissolution controlled Release system
3.Diffusion & Dissolution controlled Release systems
4.Ion exchange resins
5.pH independent systems
6.Osmotically controlled Release systems
7.Altered density formulation / buoyant systems

4. 1)DIFFUSION CONTROLLED SYSTEMS
 Major process for absorption.
 No energy required.
 Drug molecules diffuse from a region of higher concentration to
lower concentration until equilibrium is attained.
 Directly proportional to the concentration gradient across the
membrane.
MONOLITHIC-MATRIX SYSTEMS
The drug is uniformly dispersed in a polymer matrix and release is
controlled by its diffusion from the matrix into the surrounding
environment.

5. Matrix system
 Also called as Monolith dissolution controlled system.
 Controlled dissolution by:
1.Altering porosity of tablet.
2.Decreasing its wettability.
3.Dissolving at slower rate.
 First order drug release.
 Drug release determined by dissolution rate of polymer.
Examples:
Dimetane extencaps, Dimetapp extentabs.

6. Types of matrix systems
 Two types of matrix systems
1.Slowly eroding matrix
2.Inert plastic matrix
1.Slowly eroding matrix
Consists of using materials or polymers which erode over a period
of time such as waxes, glycerides, stearic acid, cellulosic materials
etc.
Principle:
• Portion of drug intended to have sustained action is combined
with lipid or cellulosic material and then granulated.
• Untreated drug granulated
• Both mixed

7. 2.Inert plastic matrix
Principle:
 Drug granulated with an inert, insoluble matrix such as polyethylene,
polyvinyl acetate, polystyrene, polyamide or polymethacrylate.
 Granulation is compressed results in MATRIX
 Drug is slowly released from the inert plastic matrix by leaching of body
fluids
Release of drug is by diffusion.

8. Materials used as retardants in matrix tablet
formulations:
MATRIX
CHARACTERISTICS
MATERIAL
Hydrophobic carriers
(a) Insoluble, inert
matrix
(b) Insoluble,
erodable
Polyethylene
Polyvinyl acetate
Polyvinyl chloride
Ethyl cellulose
Carnauba wax
Polyethylene glycol
Fatty alcohol
Fatty acids
Hydrophilic carriers Methyl cellulose
Hydroxy Ethyl cellulose
HPMC
CMC,
Na CMC
Sodium alginate

9. 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

10. Higuchi Equation
Q = DE/T (2A.E Cs)Cs.t)1/2
Where ,
Q=amount 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.

11. RESERVOIR SYSTEMS
 The drug is contained in a core, which is surrounded by a polymer
membrane & release by diffusion through the rate limiting membrane.
 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 steps : Polymeric content in coating, thickness of
coating, hardness of microcapsule.
 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

12.  The rate of drug release explained by Fick's law of
diffusion.
Dm/dt = DSK(AC)/L
Where,
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.

14. DIFFUSION CONTROLLED SYSTEMS
Matrix system Reservoir system
Achievement of zero order-
difficult
Achievement of zero order is
easy
No danger of dose dumping Rupture can result in
dangerous dose dumping
Not all drugs can be blended
with a given polymeric matrix
Drug inactivation by contact
with the polymeric matrix can
be avoided
Can deliver high molecular
Weight compounds
Difficult to deliver high mol.
wt compounds

15. 2) DISSOLUTION CONTROLLED RELEASE SYSTEMS
Two classes:
1.Matrix dissolution control
2.Encapsulation dissolution control
1.Matrix dissolution control
 The rate of penetration of dissolution fluid in to the matrix
determines the drug dissolution and subsequent release.

16. 2.Encapsulation dissolution control
 Systems involve coating of individual particles of drug with a slow
dissolving material & the coated particles can be compressed directly
into tablets or placed in capsules.
 Called as Coating dissolution controlled system.
 By Microencapsulation OR By altering layers of drug with rate-
controlling coats.
 Dissolution rate of coat depends upon stability & thickness of coating.
 Masks colour, odour, taste,minimising GI irritation.
Examples: Ornade spansules, Chlortrimeton Repetabs

17.  If the dissolution process is diffusion layer
controlled where the rate of diffusion solid surface
through a unstirred liquid film to bulk solution is
rate limiting the flux is ‘j’ is given by,
J=-D(dc/dx)
Where,
D= Diffusion coefficient.
dc/dx = concentration gradient between the
solid surface and bulk of solution.

18. 3) DIFFUSION & DISSOLUTION CONTROLLED
RELEASED SYSTEMS
Release rate is dependent on
-Fraction of soluble ingredient in the coating
-Diffusion coefficient of drug though pore in coating
-Concentration of drug in dissolution media
-Concentration of drug in core.

19.  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.

20. 4) ION-EXCHANGE RESINS
 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 divinyl benzene
sulphonate. In tablet formulations ionexchange resins have
been used as disintegrant.

21. 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.

23. Advantage:
For drug that are highly susceptible to degradation by
enzymatic process.
Limitation:
Variable diet, water intake.. can affect the release rate of
drug.
 Sustained delivery of ionizing acidic & basic drug can be obtained
by complexing them with insoluble non-toxic anion exchanger
and cation exchanger resin respectively.
 Here the drug is released slowly by diffusing through the resin
particle structure.
 The complex can be prepared by incubating the drug-resin
solution or passing the drug solution through a column
containing ion exchange resin.

24. 5) 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.

25. 6) OSMOTICALLY CONTROLLED RELEASE SYSTEMS
 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.
 The drug is activated to release in the solution form at a
constant rate through a special delivery orifice.

26.  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)
Where,
K, A & h= Membrane permeability, effective surface area &
thickness of semi permeable membrane,
Δπ= osmotic pressure difference,
Δp= hydrostatic pressure difference.

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

28. Oral osmotic pumps
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.

29. 7) ALTERED DENSITY SYSTEM
 These are also called floating systems or hydro dynamically
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.

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