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Controlled drugdeliverysystem
1. Osmotically Controlled Systems
• osmotic pressure provides the driving force to generate
controlled release of drug.
• Consider a semipermeable membrane that is permeable to
water, but not to drug. When this device is exposed to water or
any body fluid, water will flow into the tablet owing to the
osmotic pressure difference.
dV/dt= Ak/h(∆Π−∆P)
k=membrane permeability, A=area of the membrane, h=membrane thickness
∆Π = osmotic pressure difference, ∆P =hydrostatic pressure difference
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2. 2
Type A contains a osmotic
core with drug
Type B contains the drug
solution in a flexible bag,
with the osmotic core
surrounding
4. Characteristics of Osmotically Controlled Devices
Advantages
Zero-order release is obtainable
Peformulation is not required for different drugs
release of drug is independent of environment of the system
Disadvantages
systems can be very expensive
quality control is more extensive
4
5. Hydrodynamic Pressure Controlled
Systems
• Hydrodynamic pressure generated by swelling of a hydrophilic
gum
• The device comprises of a rigid, shape retaining housing
enclosing a collapsible, impermeable containing liquid drug
• The gun imbibes water in GIT through an opening at the lower
side of external housing and swells creating an hydrodynamic
pressure
• The pressure thus created squeeze the collapsible drug reservoir
to release the medicament through the delivery orifice
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6. Principle:-
In this system a semipermeable membrane around a core of an
osmotically active drug or a core of an osmotically inactive drug in
combination with an osmotically active salt. The drug either in the from
of solid or as solution. Semipermiable housing having controlled water
permeability,the drug is activated to release in solution form at a constant
rate through a special delivery orifice.
If the drug is solution so the intrinsic rate of drug release
Q/t is given by: Q/t = Pw Am /hm (πs-πe )
If the drug is solid so the intrinsic rate of drug release
Q/t is given by: Q/t = Pw Am /hm (πs-πe)Sd
where, Pw = water permeability, Am = effective surface area,
hm = thickness of the semipermiable housing,
(πs-πe)=deferential osmotic pressure b/w drug delivery system and
external environment,
Sd=aqueous solubility of the drug contained in solid formulation.
7. Materials used
Semipermiable membrane Hydrophilic and hydrophobic polymers
Wicking agents Solubilizing agents Surfactants Coating solvents
Plasticizers Flux regulators Pore forming agents
Classification of osmotic pumps
Oral osmotic pumps ,Elementary osmotic pump,Push-pull osmotic
pump ,Controlled porosity osmotic pumps,Osmotic bursting osmotic
pumps,Combination of effervescent agents with the drug Pump for
insoluble drugs,Sandwiched Osmotic tablet systems
Elementary osmotic pump It consists of an osmotic core containing
drug which is coated with semi permeable membrane usually cellulose
acetate with delivery orifice. The core may or may not contain an
osmotic agent depending upon the osmotic activity of the drug.
8.
9. Mechanism :-The water penetrates inside the dosage form at the rate
determined by the fluid permeability of the membrane and osmotic
pressure of core formulation. This will result in formation of saturated
solution of drug within the core, which is dispensed at a controlled rate
from the delivery orifice in the membrane.
Push-pull osmotic pump:-It is a modified elementary osmotic pump
through which it is possible to deliver both poorly water soluble and
highly water soluble drugs at a constant rate. After coming in contact
with the aqueous environment, polymeric osmotic layer swells and
pushes the drug layer, and thus releasing drug in the form of fine
dispersion via the orifice.
Controlled porosity osmotic pumps:-This type of osmotic pump
consists of 2 layers of membrane.The inner is microporous membrane,
which is made up of cellulosic material containing some pore forming
agents, covered by a semipermeable membrane.When the system is
placed in an aqueous environment the soluble components of first
layer of coating dissolve, resulting in a microporous membrane, which
provides greater flux of water into the system
10. MICROPOROUS MEMBRANE:-
Osmotic bursting pumps:-
When it is placed in an aqueous environment, water is
imbibed and hydraulic pressure is built up inside until the
wall ruptures and the contents are released to the
environment.Varying the thickness as well as the area the
semipermeable membrane can control release of drug. This
system is useful to provide pulsated drug release.1
Sandwiched osmotic tablets:-
It is composed of polymeric push layer sandwiched between
two drug layers with two delivery orifices. When placed in
the aqueous environment the middle push layer containing
the swelling agents swells and the drug is released from the
two orifices situated on opposite sides of the tablet and thus
SOTS can be suitable for drugs prone to cause local
irritation of the gastric mucosa.
11. SEMI PERMEABLE MEMBRANE WITH PLASTICIZER
Advantages of osmotic drug delivery Delivers drug at
zero order release kinetics. Delivery rate is independent of
pH and outside agitation. Delivery of drug takes place in
solution form which is ready for absorption. Due to its zero
order release profile it is used in very early stages of drug
research, such as drug screening, animal toxicology and
pharmacology.19. Limitations
Disadvantages of osmotic drug delivery Special
equipment is required for making an orifice in the system.
Residence time of the system in body varies with the gastric
motility and food intake. It may cause irritation or ulcer due
to release of saturated solution of drug. Costly process.
12. HYDRODYNAMICALLY BALANCED DRUG DELIVERY
SYSTEM.
Hydrodynamically balanced system are also known as floating
drug delivery system.In this system the reservoir is
homogenously dispersed in a swellable polymer matrix
fabricated from a hydrophilic polymer..
PRINCIPLE
In GIT the laminate absorbs GI fluids & become increasingly
swollen, which generate hydrodynamic pressure in the
system,the hydrodynamic pressure thus created forces the drug
reservior compartment to reduce in volume and causes the liquid
drug formulation to release through the delivery orifice at a rate
defined by :- Q / t=Pf Am/ hm( s - e) Pf = Fluid permeability,ɵ ɵ
Am = Effective surface area , hm= Thickness of wall with
annular openings, ( s - e )= Difference in the hydrodynamicɵ ɵ
pressure between the drug delivery system( s) & theɵ
environment ( e).ɵ
13. HYDRODYNAMICALLY ACTIVATED DRUG DELIVERY SYSTEM
Hydrodynamic pressure activated drug delivery system can be
fabricated by enclosing a collapsible, impermeable container,
which contains a liquid drug formulation to form a drug reservoir
compartment.Inside a rigid shape retaining housing a composite
laminate of an absorbent layer and a swellable hydrophilic
polymer layer is sandwiched between the drug reservoir
compartment and the rigid housing.
Types of Hydro dynamically balanced system
1. Effervescent system
2. Non Effervescent system
EFFERVESCENT SYSTEM
These floating drug delivery system are prepared in such a
manner that when they come in contact with stomach fluid , CO2
is generated, & remain entrapped in hydrocolloid gel. This leads
to an upward flow of the dosage form and maintains it in a
floating condition.
14. 09/08/2010 KLE COP, NIpani 14
Multiple-unit oral floating drug delivery system
.
(A)Multiple-unit oral floating drug delivery system.
(B)Working principle of effervescent floating drug delivery
system.
Multiple-unit oral floating drug delivery system
28Figure . (A) Multiple-unit oral floating drug delivery
system. (B) Working principle of effervescent floating drug
delivery system.
15. 15
NON EFFERVESCENT SYSTEM:
It consists of two major components: Gel forming or swellable cellulose
type of hydrocolloids & polysaccharides. Matrix forming polymers
(polycarbonate, polyacrylate, polymethacrylate & polystyrene).
MECHANISM
Gel forming hydrocolloids swells in contact with gastric fluid after oral
administration and maintains a relative integrity of shape and a bulk
density of less than unity within gastric environment. The air thus
trapped by the swollen polymer imparts buoyancy to the dosage
form.The gel barrier controls the rate of solvent penetration into the
device & the rate of drug release from the device.
It maintains a bulk density of <1 and thus remains buoyant in the gastric
fluid inside the stomach for upto 6 hrs; conventional dosage forms
disintegrate completely within 60 min and are emptied totally from the
stomach shortly afterward.
Advantages of HBS:-Delivery of drugs for local action in stomach.
Minimizing the mucosal irritation due to drugs, by drug releasing slowly
at controlled rate Site specific drug delivery.
16. Treatment of gastro intestinal disorders such as gastro-
esophageal reflux.Simple and conventional equipments
required for manufacture.Ease of administration and
better patient compliance.
pH- Activated Drug Delivery :-
This type of activation controlled drug delivery system
permits targeting the delivery of drug only in the region
with the selected pH range. Drugs administered orally
would encounter a spectrum of pH ranging from 7 in
the mouth, 1 - 4 in the stomach and 5 - 7 in the
intestine. Prepared by first blending an acidic or basic
drug with one or more buffering agents (Eg. primary,
secondary, tertiary salt of citric acid) granulating with
appropriate pharmaceutical excipients to form small
granules and then coating the granules with a
gastrointestinal fluid permeable film forming polymer
(Cellulose derivatives).
17. 17
The polymer coating controls the permeation of gastrointestinal fluid.
The gastrointestinal fluid permeating into the device is adjusted by the
buffering agents to an appropriate constant pH, at which the drug
dissolves and is delivered through the membrane at a constant rate
regardless of the location of the device in the alimentary canal. It is also
fabricated by coating the drug containing core with a pH sensitive
polymer combination
For instance, a gastric fluid labile drug is protected by encapsulating it
inside a polymer membrane that resists the degradative action of gastric
pH, such as the combination of ethyl cellulose and hydroxyl methyl
cellulose phthalate. In the stomach, coating membrane resists the action
of gastric fluid (pH<3) & the drug molecule is thus protected from acid
degradation.
After gastric emptying the drug delivery system travels to the small
intestine and the intestinal fluid solubulize the hydroxyl methyl cellulose
phthalate component from the coating membrane. This leaves a
microporous membrane of intestinal fluid insoluble polymer of Ethyl
cellulose, which controls the release of drug from the core tablet.
18. The drug solute is thus delivered at a controlled manner in the
intestine by a combination of drug dissolution and pore channel
diffusion
Cellulose acetate tri-melliate.
Cellulose acetate phthalate
Poly vinyl acetate phthalate
Hydroxy propyl methyl phthalate-50
Eudragt –D 30
Eudragt –L100
Eudragt –S100
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19. Ion-Exchange Systems
• Ion-exchange systems generally use resins composed of water
soluble cross-linked polymers
• These polymers contain salt forming functional groups in
repeating position on the polymer chain
• The drug is bound to the resin and released by exchanging with
appropriately charged ions in contact with the ion exchange
groups
Resin+
- drug-
+ X-
resin+
- X-
+ drug-
WhereX-areionsin theGItract
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20. ION EXCHANGE RESINATES AS CONTROL DRUG
DELIVERY SYSTEM
Principle A Cation exchange resin generally has Sulphonic
and Carboxylic functional groups as an integral part of the
resin and an equivalent amount of cationic drug molecules.
An Anion exchange resin generally has quaternary
ammonium groups and polyalkylamine functional groups as
an integral part of the resin and an equivalent amount of
anionic drug molecules.
Types of ion-exchange resins
Drugs Suitable for Resinate Preparation Drugs should have
acidic and basic groups in their chemical structure.
Biological half life should be between 2-6 hrs, drugs with
t1/2 < 1 hr or > 8 hrs are difficult to formulate. The drug is to
be absorbed from all regions of GI tract. Drugs should be
stable sufficiently in the gastric juice09/08/2010 KLE COP, NIpani 20
21. Some Important Properties of Ion-Exchange Resins Particle
Size and form Porosity Swelling Ion exchange capacity
General preparation of drug resinatesColumn process:
A highly concentrated drug solution is eluted through a bed
or column of the resin until equilibrium is established.
Batch process: The resin particles are stirred with a large
volume of concentrated drug solution.
AdvantagesIon – exchange resonates of drug can help in
reducing the dose.Reduced fluctuations in blood and tissue
concentration level can be achieved.Protection of drug from
gastric enzymes.Controlled release.
LimitationsThe release rate is proportional to the
concentration of the ions present in the area of
administration.The release rate of drug can be affected by
variability in diet, water intake and individual intestinal
content. 21