Implants drug

delivery systems

Presented by:
V.L. Pavan Raju
11T15s0913
Industrial Pharmacy
Avanthi institute of Pharmaceutical sciences

What are Implants?????

What is the main reason to use

Implants????

What are the sites the Implants were

administrated???

Implants are one of the Advances in drug delivery systems.

Implantable drug delivery systems are designed to transmit
drugs and fluids into the bloodstream without the repeated
insertion of needles.
Implantable drug delivery systems are placed completely
under the skin usually in a convenient but inconspicuous
location.
The patient is aware of only a small bump under the skin.
They are meant for selective drug to its site of action and
intended for target drug delivery.
The action of the drug will last for long period of time for
several days to years.

Charactertics:
Non-Inflammatory
Non-irritant
Non- Antigenic
Non- Carcinogenic
Non-Thrombogenic
Should be long reservoir
Better Life
Easy programmable

TYPES OF IMPLANT DRUG DELIVERY SYSTEMS

IDDS can classified into 3 main

categories

Non-Biodegradable
2) Biodegradable
Implantable pump systems and
Atypical class of implants
1)

3)

1.Non-Biodegradable
Either in biodegradable or in nonbiodegradable the implants are available as
matrix system or in reservoir systems.
The release kinetics of the drug from these
implants systems depends upon both
solubility and diffusion coefficient.
A disadvantage of this system is it requires
minor surgery to remove the implants from
the body after diffusion of the drug.

POLYMERIC MATRIX SYSTEM

The drug is dispersed homogenously

inside the matrix.

Slow diffusion of drug through the
polymeric matrix provide the sustain
release.
Polymethylmethacrylate(PMMA) has used commonly for
formation of matrix system.
SEPTOPAL is a Gentamycin implant formulated as
chains and minichains and is mainly used in the
treatment of ostemyelitis and Osteitis.
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SEPTOPAL

THE RESERVOIR SYSTEM

It consists of compact drug core surrounded by a

permeable Non-biodegradable membrane.
Based on the thickness of permeability membrane
the control release of drug diffusion in body depends.
The concentration of drug within the reservoir is in
constant equilibrium with the inner surface of the
enclosed member, the driving force for diffusion
release of the agent is constant.
Then zero order release kinetics is obtained.

Mechanism of Matrix
and reservoir type
system release

NORPLANT

system has a hormone

Levonorgestrel, encapsulated in a silicone
membrane used as implant intradermally.
It is kept inside the of the upper arm to provide
contraception in women by sustain release.
This type of implant last for upto 5 years.
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2.BIODEGRADABLE
IMPLANTS

Biodegradable polymer are highly desirable for drug delivery

application, as the device will be disappear over time. Thus able to
eliminate the second surgical procedure to retrieve the device.
In recent days biodegradable implants are used widely of molecules has
increased considerable.
Mostly used for Musculoskeletal pathological, to carry proteins &
antibiotics treat osteomyelitis.
MAIN CONSIDERATION IN RESERVIOUR TYPE
BIODEGRADABLE

The degradation rate of polymer surrounded the drug should be slower

rather than the drug diffusion rate.
Therefore it remains intact while the drug is released completely.
After drug diffusion completely the polymeric membrane is degraded in
vivo and eliminated.

Degradable polymers currently used

ALIPHATIC POLYESTRS:

Polylactic acid (PLA)

Polyglycolic acid (PGA)
Polydioxanone (PDS)
These polyesters with poly caprolactone (PCL), polyanhydrides
and polyphosphazenes (POPs) substituted with amino acid are mostly
used.
The above mentioned polymers are approved by
FOOD AND DRUG ADMINISTRATION (FDA)
Cross linked protein
Polydihydropyrons

ZOLADEX implant is a sterile

biodegradable product containing
Goserelin acetate equivalent to 10.8mg of
goserelin. It is injected as single use
syringe presented as white-cream colored
1.5mm diameter cylinder.
It is designed as subcutaneous
implantation with continuous
release over a 12 weak period.

3.PUMP SYSTEM IMPLANTS

The implantation is also
processed by the pump system, the various widely
used pump system are listed below.

a) Implantable Pump System

b) Osmotic Pump System
c) Duros Pump System

IMPLANTABLE PUMP SYSTEM

Pump system is provided external control of delivery
rate and volume. Controlled release of drug from
an implantable pump is generally achieved by
utilising the micro-technology of electronic system.

The pump consists of a disc shaped canister made of light

weight biocompatible titanium. Below it is separated into 2
chambers.

1st chamber consists of cfcs propellants and 2 nd chamber

consists of drug formulation.

The gas pushes the drug through a filter and flow regulator
provides a constant rate drug release. The delivery rate
adjusted by changing drug concentration in reservoir.

The advantage of this system is no external energy is

required to drive the pump action.

When the pump reservoir needs to be refilled, an injection

of the drug administrated through Teflon septum.

OSMOTIC PUMP SYSTEM

The Osmotic pump has a drug reservoir surrounded

by a chemically inert and impermeable flexible wall.
Outside the reservoir wall Osmotic sleeve is present,
a cylinder containing a high concentration of Sodium
chloride is placed, this creates the osmotic
difference between the compartment and the
aqueous environment.
When pump is inserted into the body the water
present externally enters into the pump through the
membrane and compresses the reservoir space, thus
resulting in exerting the drug out.

DUROS TYPE PUMP

DELIVERY
Duros implant is a miniature cylinder made from a

titanium alloy, which protects and stabilizes the drug

inside using ALZA proprietary formulation technology.
Water enter into one end of the cylinder through a
semipermeable membrane, the drug is delivered from
port of the other end.
This non-biodegradable, osmotically driven system used
to small drugs proteins, bioactive macromolecules for
systemic or tissue specific therapy.

ATYP IC A L SYSTEM

a)

This type is recently developed which

differs from typical implants.
Ceramic composite system:
CDDS are used to
deliver proteins, steroids, amino acids, phenolics, vaccines
and antibiotics.

i.

Inorganic bone meal: These contains of fragments pieces of

bones from various parts of the body and used for bone
autograft. As they are collected from patient own bone
system, they are biocompatible and readily accessible.

ii.

Hydroxyapatite Ceramics: They are delivered to the skeletal

tissue at therapeutic concentration. The hydroxyapatite

loaded with antibiotics like Cephalexin, Norfloxacin are placed

b) Intrauterine Implants:
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Progestasert an intrauterine device by ALZA

corporation delivers a constant progesterone

through this implant.
Physically the device consists of a T-shaped
polyethylene support whose vertical arm is fitted
with a sleeve containing the steroid.
The sleeve consists of inner reservoir of steroid and
a silicon polymer and an outer rate regulating layer
of polyethylene-vinyl acetate.

c) Insitu gel forming formulations:

Liquid formulations that generate as solid

depot after subcutaneous injection also

designated as implants.
Features:
The application is less invasive and painful than
general implants.
Localised systemic delivery, can achieve for prolonged
period of time from one to several months.
Various therapeutic agents can be incorporated by
simple mixing.
The 2 methods of this system are:
I. Solvent Exchange method
II. Thermally induced gelling

i. Solvent Exchange method

It consists of, dissolving a water insoluble polymer, in a water

miscible biocompatible solvent.

When injected on contact to the body fluid, the solvent diffuses
out of the polymer matrix.
Due to its insolubility in water, the polymer precipitates and form
as solid.
ATRIGELR a biodegradable polymer given by subcutaneous by
using cannula, the drug encapsulated within the implant and
controlled release manner exhibits.
Atrigel is currently used for delivery of Leuprolide acetate to
treat the prostate cancer.

ii) Thermally induced gelling

type
They

exhibits thermo-rheological properties,

the polymer is solution at room temperature
and converts to gel at body temperature.
ReGel is a thermosentitive, biodegradable
triblock copolymer (PLGA-PEG-PLGA) in
phosphate buffer saline (pH7.4) comprises
biocompatible component poly lactide-coglycolide and Polyethylene glycol(PEG)
Paclitaxel is administrated by the OncoGel
acts as anti-neoplastic agent.
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IMPLANTABLE DRUG DELIVERY ON THE

IMPLANT
TRIALS/FDA
DELIVERY
DRUG/DOSE
DURATION
MARKETAPPROVAL
Reservoir type:
Vitrasert
(pSivida, licensed to
Bausch & Lomb)

1996 FDA approval for

CMV retinitis

Surgical implantation
Ganciclovir 0.45 mg
into posterior segment
through 5.5-mm pars plana
incision.

5 to 8 months

Retisert
(pSivida,licensed to
Bausch &Lomb)

2005 FDA approval for

chronic noninfectious
uveitis

Surgical implantation into Fluocinolone acetonide 0.59 30 months

posterior segment through mg
3.5-mm pars plana incision.

I-Vation (SurModics)

Phase 1 trial
for treatment of DME

Surgical implantation
Triamcinolone acetonide 1
through a 25-gauge needle g/day or 3 g/day
with conjunctival cut-down.

Biodegradable Implants:
Ozurdex, previously
Posurdex (Allergan)

2009 FDA approval for

macular edema due to vein
occlusion

Surgical implantation
Dexamethasone 350 or 700 6 months
through 20-gauge incision or g
22-gauge injection.

New Approach:
Lucentis in microparticles
(SurModics,licensed to
Genentech)

In development

Biodegradable
microparticles.

Not yet determined

NT-501 (Neurotech
Pharmaceuticals)

Phase 2 study
of dry AMD

Genetically engineered
human retinal pigment
epithelium cells with
transfected plasmids
encoding a therapeutic
protein cells are loaded into
a polymer membrane cap.

Ciliary neurotrophic factor. Up to 18 months

High dose: 203,000 cells
released at 800 ng per 1 x
106 cells/day

Up to 2 years

Not yet determined

References:
Controlled Drug Delivery- concepts and
advances by S.P. Vyas and R.K. Khar.
Controlled and Novel Drug delivery by N.K. Jain,
Novel Drug Delivery system by Y.M. Chien,
Marcel Dekker
Journal of Neurosciences Method, A fully
implanted drug delivery system, Volume 182,
Issue2, 15 September 2009, Pages 165171
Journal of Pharmacy & Pharmaceutical Sciences,
Design and evaluation of a novel floating
osmotic pump system, Pg no: 129-137,