Implants are cylindrical, monolithic devices of millimeter or centimeter dimensions, implanted into the subcutaneous or intramuscular tissue by an minor surgical incision or injected through a large bore needle; and release the incorporated drug in a controlled manner, allowing the adjustment of release rates over extended periods of time, ranging from several days up to one year.
2. Introduction
Implants are cylindrical, monolithic devices of millimeter or centimeter
dimensions, implanted into the subcutaneous or intramuscular tissue by
an minor surgical incision or injected through a large bore needle; and
release the incorporated drug in a controlled manner, allowing the
adjustment of release rates over extended periods of time, ranging from
several days up to one year.
Implantable drug delivery systems are placed completely under the skin.
The patient is aware of only a small bump under the skin.
Designed to transmit drugs and fluids into the bloodstream without the
repeated insertion of needles.
Well suited to the drug delivery requirements of insulin, steroids,
chemotherapeutics, antibiotics, analgesics, total parenteral nutrition,
and heparin.
There is little chance of infection or interference with daily activities
Because the device is completely subcutaneous, with no opening in the
skin.
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3. Anatomy & Physiology of Skin
Features:•Subcutaneous tissue is essentially a sheet of areolar tissue lying directly
underneath the skin.
•It is rich in fat, but poor in nerve network & hemoperfusion.
Therefore, the subcutaneous tissue is an ideal location for implantation,
slow drug absorption & low reactivity to the insertion of foreign materials. 3
7. Design & Fabrication
Approaches For The Development of Implantable Products:
(a) Controlled drug delivery by diffusion process:
Polymer membrane permeation- controlled drug delivery:a) Nonporous membranes
b) Micro porous membranes
c) Semi permeable membranes
Matrix diffusion-controlled drug delivery:a) Lipophilic Polymers
b) Hydrophilic(swellable) polymers
c) Porous polymers
Micro reservior partition- controlled drug delivery system:a) Hydrophilic reservoir/Lipophilic matrix
b) Lipophilic reservoir/Hydrophilic matrix
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8. (b) Controlled drug delivery by activation process:
Osmotic pressure
Vapor pressure
Hydration
Hydrolysis
Magnetism
(c) Controlled drug delivery by feed back regulated
mechanism:
Bioerosion
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9. Controlled drug delivery by
diffusion process
A)
Membrane permeation- controlled drug delivery:-
Here the drug formulation is totally or partially encapsulated within a
drug reservoir compartment and
the drug release surface is covered by a rate limiting polymeric
membrane having a specific permeability for drug.
drug reservoir
polymeric membrane
Drug contained in
a formulation
•
1.
2.
Encapsulation of drug formulation in to the reservoir compartment can be
done by:
Spray coating
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microencapsulation
10. Different shapes of the systems like sphere , cylinder or sheet can be
fabricated
Example:- A NORPLANT SUBDERMAL IMPLANT ,
PROGESTASERT IUD, and
OCUSERT SYSTEM.
b) Matrix diffusion-controlled drug delivery:
The drug reservoir is prepared by homogenous dispersion of drug particles
in a rate controlling polymer matrix fabricated from either a lipophillic or
a hydrophilic polymer.
The drug dispersion in a polymer matrix is done by
a) Blending finely divided drug particles with a liquid polymer or a viscous
base followed by cross linking of the polymer chain
b) Mixing the drug with a polymer at an elevated temperature
c) Dissolving drug and polymer in a common solvent followed by solvent
evaporation at elevated temperature or under vacuum
The resultant drug polymer dispersion is then molded or extruded to form a
drug delivery devices of various shapes
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11.
Example:- Contraceptive Vaginal Ring
Syncro-Mate B Implants
Compudose Implant
c) Micro reservoir Partition- Controlled drug delivery:
Drug Reservoir- fabricated by aqueous suspension of a drug using high
energy dispersion technique into a biocompatible polymer such as silicon
elastomer to form a homogenous dispersion of microscopic drug
reservoir.
Depending on the physiochemical properties of the drug and the desired
rate of drug release, the device can be further coated with polymer to
modify mechanism & rate of release.
Example:- Syncro-Mate C Implants
Dual-Release Vaginal Contraceptive Ring
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13. Controlled drug delivery by
activation process
Osmotic pressure activated drug delivery system:
In this type of controlled drug delivery system the release of the drug takes
place due to osmotic pressure.
Osmosis is the movement of
a solvent through a semi-permeable
membrane from a region of low- solute
concentration to a region of highsolute concentration.
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14.
Drug reservoir which can be either a solid or a suspension is contained in a
semi permeable housing .
The release is activated through a specially formed orifice and rate of
release is modulated by controlling the osmotic gradient.
The release rate is dependent of:
water permeability of membrane,
solubility of osmogen,
effective surface area of semipermeable housing
Representatative example of this type of implantable controlled release drug
delivery system is: ALZET Osmotic Pump
DUROS Osmotic Pump
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17.
Vapor pressure-activated implantable drug delivery system:
The drug reservoir which is a solution formulation is contained in to an
infusate chamber.
By freely movable bellow the chamber is a pumping system physically
separated from the vapors pressure chamber which contains vaporizable
fluids such as a fluorocarbon.
The fluorocarbon vaporizes at body temperature creating a vapor pressure
that pushes bellow to move upward and forces the drug solution to get
delivered .
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19.
Bioerosion regulated drug delivery system:
This system consist of a drug dispersed in to a biodegradable polymer
matrix like poly vinyl methyl ether and is coated with immobilized urease in
a neutral pH.
In the presence of urea, urease at the surface of drug delivery system
metabolize urea to form ammonia causing increase in pH at which polymer
degrades leading to drug release.
Hydrocortisone release
Urease
U
U
U
U
U
Erosion
U
U
Hydrocortisone
U
Urea
Ammonia
Alkaline pH
U
U
U
U
U
U
U
Polymer
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20. Targeted Drug Delivery With
Catheterized Osmotic Pumps:
Catheters of different designs can be attached to the exit port
of an osmotic pump for targeted drug delivery
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21. Electrical Regulated Release:
Device features:
Target: 1+ year implant life.
100 to 400 doses.
Reservoir volume ≥100 nL.
Accommodates solutions, solids.
Individual reservoirs activated
electronically
– Each reservoir can contain a different drug or formulation
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22.
E.g. Silicon Microchip
contained an array of reservoirs attached in silicon. The reservoirs were
capped with gold membranes that could be electrochemically dissolved in
saline with an applied voltage (through a wireless signal from outside the
body). At approximately 1 V, gold chloride is formed, causing the
membrane to dissolve.
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23. Micrographs of gold membranes
(a) before and (b) after electrochemical
dissolution
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24. Advantages:
◦ Controlled drug delivery for over a long time
(months/years)
◦ Improve patient compliance
◦ Targeted drug delivery
◦ Bypass first pass metabolism
◦ Decrease side effects
◦ Improved stability of drug
◦ Improve availability of drugs
Disadvantages:
- mini-surgery is needed
- uneasy to simply discontinue the therapy
- local reactions
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