1. Rate Controlled Drug
Delivery System
Presented By,
Nikam N.R.
M.Pharmacy1stYr,
(Pharmaceutics Dept.)
RCP, Kasegaon.
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2. Introduction
Controlled release drug delivery system can improve the
therapeutic efficacy and safety of a drug by precise
temporal and spatial placement in the body, thereby
reducing both the size and no. of doses required.
Controlled release:
System provides some actual therapeutic control whether
temporal or prolonged.
Sustained release:
System provides medication over an extended period with
the goal of maintaining therapeutic level.
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3. Classification of rate controlled drug delivery system
1.Rate-preprogrammed drug delivery system
2.Activation-modulated drug delivery system
3.Feedback-regulated drug delivery system
4.Site-targeting drug delivery system
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4. 1. Rate-preprogrammed drug delivery
SYSTEM
1. Dissolution controlled DDS
2. Diffusion controlled DDS
3. Erosion controlled DDS
4. Combination of dissolution, diffusion and erosion controlled DDs
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5. 2. ACTIVATION-MODULATED DRUG DELIVERY
System
In this group of controlled-release drug delivery systems
the release of drug molecules from the delivery systems
is activated by some physical, chemical or biochemical
processes and/or facilitated by the energy supplied
externally.
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6. Activation modulated drug delivery systems(DDS) can be
classified into following categories:
1. Physical means
a. osmotic pressure activated DDS
b. hydrodynamic pressure activated DDS
c .vapor activated DDS
d. mechanically activated DDS
e. magnetically activated DDS
f. sonophoresis activated DDS
g. iontophoresis activated DDS
h. hydration-activated DDS
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7. 2. Chemical means
a. pH-activated DDS
b. ion-activated DDS
c. hydrolysis-activated DDS
3. Biochemical means
a enzyme activated DDS
b. biochemical-activated DDS
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8. Mechanically activated drug
delivery systems
In this type of activation-controlled drug delivery system
the drug reservoir is a solution formulation retained in a
container equipped with mechanically activated pumping
system.
• The volume of solution delivered is controllable as small
as 10-100μl.
• The volume of solution delivered is independent of the
force and duration of activation applied as well as the
solution volume in the container.
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9. • Example, is the development of the metered-dose
nebulizer for the intranasal administration of a precision
dose of buserelin, which is a synthetic analog of
luteinizing hormone releasing hormone (LHRH) and
insulin.
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10. Ph Activated drug delivery systems
This type of DDS permits targeting the delivery of a
drug only in the region with a selected pH range.
• Intestinal pH activated DDS
It is fabricated by coating the drug containing core with
a pH sensitive polymer combination.
A gastric fluid labile drug is protected by encapsulating
it inside a polymer membrane that resist the
degradative action of gastric ph. such as the
combination of ethyl cellulose and HMC phthalate.
The drug is release by drug dissolution and pore
channel diffusion mechanism.
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11. In the stomach the coating membrane resists the action
of gastric fluid (ph < 3) and the drug ,molecules are thus
protected from acid degradation.
After gastric emptying the drug delivery system travels
to the small intestine and the intestinal fluid activates
the erosion of the intestinal fluid-soluble HMC
phthalate component from the coating membrane.
By adjusting the ratio of the intestinal fluid soluble
polymer to the intestinal fluid insoluble polymer, the
membrane
permeability of a drug can be regulated as desired.
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12. Osmotic activated drug delivery
system
Osmosis can be defined as “the net movement of water
across a selectively permeable membrane driven by a
difference in osmotic pressure across the membrane.”
It is driven by a difference in solute concentrations
across the membrane that allows passage of water, but
rejects most solute molecules or ions.
Osmotic pressure created by osmogen is used as driving
force for these systems to release the drug in controlled
manner.
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13. Osmotic pump offers many advantages over other
controlled drug delivery systems, that is,
1. They are easy to formulate.
2. Simple in operation.
3. Improved patient compliance with reduced dosing
frequency and more consistence.
4. Prolonged therapeutic effect with uniform blood
concentration.
5. Inexpensive and their production scale up is easy.
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14. Osmotic drug-delivery systems suitable for oral
administration
typically consist of a compressed tablet core that is
coated with a semi permeable membrane coating. This
coating has one or more delivery ports through which a
solution or suspension of the drug is released over time.
The core consists of a drug formulation that contains an
osmotic agent and a water swellable polymer.
The rate at which the core absorbs water depends on
the osmotic pressure generated by the core
components and the permeability of the membrane
coating.
As the core absorbs water, it expands in volume, which
pushes the drug solution or suspension out of the tablet
through one or more delivery ports.
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15. Enzyme activated drug delivery
system
This type of activation modulated DDS depends on the
enzymatic process to activate the release of the drug.
In this system the drug reservoir is either physically
entrapped in microspheres or chemically bound to the
polymer chains from biopolymers, such as albumins or
polypeptides.
The release of drug is activated by the enzymatic
hydrolysis of biopolymers by a specific enzyme in the
target tissue.
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16. Typical example of this enzyme activated DDS is,
The development of albumin microspheres that release 5-
fluorouracil in a controlled manner by protease activated
biodegradation.
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17. 3.Feedback regulated drug delivery
system
In this group of controlled-release DDS the release of
drug molecules from the delivery systems is activated
by triggering agent, such as a biochemical substance, in
the body.
The rate of drug release is then controlled by the
concentration of triggering agent detected by a sensor
in the feedback-regulated mechanisms.
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18. It is classified into the following:
1) Bioerosion-regulated drug delivery systems
2)Bioresponsive drug delivery systems
3)Self regulating drug delivery systems
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19. 1.Bioerosion-regulated drug delivery
system
The feedback-regulated DDS was applied to the
development of a bioerosion-regulated DDS by heller
and trescony.
The system consist of drug dispersed bioerodible
matrix,
fabricated from poly(vinyl methyl ether) half-ester ,
which was coated with a half layer of immobilized
urease.
In a solution of neutral pH, the polymer only erodes
slowly.
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20. In the presence of urea, urease at the surface of DDS
metabolizes urea to form ammonia.
This causes the pH to increase and a rapid degradation
of polymer matrix as well as the release of drug
molecules.
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21. 2.Bioresponsive drug delivery
system
Bioresponsive DDS was developed by Horbett et
al.
Drug reservoir is contained in a device enclosed by a
bioresponsive polymeric membrane whose drug
permeability is controlled by the concentration of a
biochemical agent in the tissue where the system is
located.
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22. • Typical example of this bioresponsive DDS is ,
The development of a glucose-triggered insulin delivery system
in which the insulin reservoir is encapsulated within a hydrogel
membrane having pendent NR2 groups.
In alkaline solution the –NR2 groups are neutral and the
membrane is unswollen and impermeable to insulin.
Glucose is a triggering agent, penetrates in to the
membrane , it is oxidized enzymatically by the glucose
oxidase entrapped in the membrane to form gluconic
acid.
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23. The –NR2 groups are protonated to form –NR2H and the
hydrogel membrane then becomes swollen and permeable
to insulin molecules.
glucose oxidase
Glucose + O2 Gluconic acid + H2O2
The –NR2 groups are protonated to form –NR2H and the
hydrogel membrane then becomes swollen and
permeable to insulin molecules.
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24. 3. Self-regulating drug delivery
systems
This type of feedback-regulated drug delivery system
depends on a reversible and competitive binding
mechanism to activate and regulate the release of
the drug.
In this system the drug reservoir is drug complex
encapsulated within a semipermeable polymeric
membrane.
The release of drug is activated by the polymeric
membrane of a biochemical agent from the tissue in
which the system is located.
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25. Example:
Sugar molecules by lectin into the design of self-regulating
DDS.
It first involves the preparation of biologically active insulin
derivatives in which insulin is coupled with a sugar(maltose)
and this into an insulin-sugar-lectin complex.
Complex is then encapsulated within a semipermeable
membrane.
As blood glucose diffuses into the device and competitively
binds at the sugar binding sites in lectin molecules.
This activates the release of bound insulin-sugar derivatives.
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