Implant drug delivery system

1. IMPLANT DRUG DELIVERY
SYSTEM
Presented by
Dasara Thanmayi

2. ABSTRACT
Implantable drug delivery systems are being
developed to release drugs to the blood stream
continuously as well as free patients from being
hospitalized to receive intravenous infusions or
frequent injections. One technique is implantation of
a pellet in the subcutaneous tissue so the pellet may
be released by erosion. Drugs are also diffused
through silicone rubber capsules but only poly
acrylamide is able to release large molecules .
Contraceptive rings containing progesterone and
placed in the uterus or vagina and implanted silicone
rubber capsules use these principles.

3. INTRODUCTION
 Implants are intended for implantation in the
body(usually subcutaneously) for the purpose of providing
continuous release of the drug over long period of time.
 Implants are administered by means of a suitable special
injection or surgical incision.
 These are developed with a view to transmit drugs and
fluids into the blood stream with out the repeated insertion
of needles.
 These systems are particularly suited to the drug delivery
requirements of insulin, steroids, chemotherapeutics,
antibiotics, analgesics, trial parenteral nutrition and heparin.

4. IDEAL PROPERTIES OF IMPLANTS:
 Bio-stable
 Bio-compatible
 Easily removable
 Non toxic and non-carcinogenic
 Minimum surface area and smooth texture
 Rate controlled release of the drug
 Non-irritant
 Non-antigenic
 Non-thrombogenic
 Should be long reservoir
 Better life
 Easy programmable

5. ENVIRONMENTALLY STABLE :
Should not breakdown under the influence of heat, light, air
and moisture.
BIO-STABLE :
Should not undergo physicochemical degradation when in
contact with bio-fluids.
BIO-COMPATIBLE :
Should neither stimulate immune responses (otherwise the
implant will be rejected) nor thrombosis and fibrosis
formation.
NON-TOXIC AND NON-CARCINOGENIC :
It’s degradation products or leached additives must be
completely safe.

6. ADVANTAGES
 Unattended continuous delivery within the
therapeutic window.
 Avoids the highly variable peak and trough
concentrations.
 Enhanced drug efficacy.
 Minimized side effects.
 Termination of therapy as and when required.
 Patient compliance is also a benefit of continuous
dosing with these implants as they operate for a long
period of time once implanted.

7. DISADVANTAGES
 Mini surgery is needed (painful).
 Uneasy to simple discontinue the therapy.
 Local reactions.
 Inadequate release.
 The reaction between host and implant.
 Implantation procedure is difficult in the case of larger
implants
 Requires small surgery for large implantation and painful.

8. APPLICATIONS:
 CANCER TREATMENT:
 GLIADEL WAFER: Delivers carmustine for the
treatment of brain tumors directly at the site of tumor to
prevent re-occurence of tumors.
 DEPOCYTE: Cytarabine releasing implantable drug
delivery system used to treat acute leukemia.
 DUROS OSMOTIC PUMP: Non bio degardable drug
delivery system used to (treat acute)deliver leoprolide
acetate in the treatment of prostate cancer.

9.  OSTEOPOROSIS:
 MICROCHIPS: This device made by ELI Lilly co
workers used to deliver for drug used to increase
bone density in patients suffering from severe
osteoporosis.
 OCULAR DISEASE:
 LACRIMEDICS: These are collagen implants used
to treat eye syndrome by partially blocking tear
removing canals and they dissolve within 7-10 days.

10. LIMITATIONS OF IMPLANTS
 Possible toxicity.
 Need for microsurgery to implant the system.
 Possible pain.
 Difficulty in shutting off release if necessary.

11. CLASSIFICATION
I. IN-SITU DEPOT FORMING SYSTEM
a) In-situ precipitating implant.
b) In-situ microparticulate implant.
c) In-situ gels.
d) In-situ cross linked gels.
I. SOLID IMPLANTS
II. INFUSION IMPLANTS

12. IN-SITU DEPOT FORMING SYSTEM
 In-situ depot forming system transform into semi-
solids upon injection and provide sustained release
of pharmacological agents.
 Including small molecule drugs, peptides.
EXAMPLE :ATRIGEL(PLGA + water)
SABER(sucrose acetate isobutyrate
ALZAMER(PLGA + solvent)

13. IN-SITU PRECIPITATING IMPLANT
 PREPARATION:
Polymeric solutions of 20%,30% and 40% dissolved in
PLGA,DMSO by shaking in an environment shaker at a
room temperature for up to 72hrs.
A clear polymeric solution was obtained and 300 mg of
MK was added to a calibrated amber glass vial and 3 ml
polymeric solution measured by 3ml syringe and added to
vial.
drug is completely dissolved in polymeric solution
volume was adjusted to 3ml calibration mark and mix well
after 24hrs.

14.  ADVANTAGES :
 Reduces the side effects.
 Improved patient compliance.
 DISADVANTAGES:
 Need for reconstitution before injection.
 Inability to remove the dose once injected.
 Relatively complicated manufacturing procedures to
produce a sterile,stable.

15. IN-SITU MICROPARTICULATE
IMPLANT
 A polymeric solution of 30% PLGA in NMP
was prepared this polymeric phase was emulsified
into an external peanut oil phase at three different
polymer to oil phase ratios of 1:1,1:2 and 1:4.
 The emulsification process was achieved by probe
sonication using branson sonifier 250 at output of
250w

16.  Frequency of 20KHZ for 30s under ice cooling
 Pluronic F6s based on the amount of the total
formulation was dissolved in the polymer phase and
aluminum monosterate in the oil phase to increase
the stability of the emulsion.
 DISADVANTAGES
 High injection force.
 Local irritation at the injection site.

17. IN-SITU GELS
 A proprietary parenteral in-situ gel delivery system
is ATRIGEL system.
 Used for both parenteral and site specific drug
delivery.
 Liquid formulations generating a semisolid depot
after adminstration into the body are attractive
delivery system.
 When the liquid polymer system is placed in the
body using standard needles and syringes.

18.  In-situ gels are drugs delivery systems that are in
solution form before administration in the body but
once administered undergo gelation in situ to form a
gel.
 In-situ routes for in situ gels :
oral, ocular, rectal, vaginal, injectable and intra-
peritoneal routes.

19. IN-SITU CROSS LINKED GELS
 Gel site polymer is a natural acidic polysaccharide.
 Extracted and purified from the aloe plant.
 The polymer in an aqueous solution forms a gel in
the presence of calcium.
 When injected subcutaneously or intramuscularly
thus entrapping a water soluble drug in the solution
and providing sustained release.

20. SOLID IMPLANTS
 Implants are cylindrical , monolithic devices of mm
or cm dimensions .
 Implanted by a minor surgical incision or injected
through a large bone needle into the subcutaneously.
 Subcutaneous tissue is an ideal location because of
its poor perfusion.
 Slow drug absorption.

21.  The drug in implants may be dissolved or dispersed
in a matrix of polymer or waxes that control release
by dissolution, bioerosin or biodegradation.
 Polymers used are silicone elastomers ,
polymethacrylates, polycaprolactone.
 While waxes include glycerol monostearate.

22. INFUSION DEVICES
These are implantable devices but are
versatile in the sense that they are intrinsically
powered to release the medicament at a zero order
rate and the drug reservoir can be replenished from
time to time . Depending upon the mechanism by
which these implantable pumps are powered to
release the contents,they are classified into
following types:

23. I. OSMOTIC PRESSURE ACTIVATED DRUG
DELIVERY SYSTEM.
II. VAPOUR PRESSURE ACTIVATED DRUG
DELIVERY SYSTEM.
III. BATTERY POWERED DRUG DELIVERY
SYSTEM.
 OSMOTIC PRESSURE POWERED SYSTEM
a) ALZET osmotic pump.
b) DUROS infusion pump.

24. ALZET OSMOTIC PUMP
 It is a miniaturized system that provides zero order
delivery of biologically active molecules and has
been extensively used in animal studies by
researchers throughout the world.

25.  The ALZET pumps are capsular in shape and made
in a variety of sizes. the pump is made of three
concentric layers.
1. The innermost drug reservoir contained in a
collapsible impermeable polyester bag(which is
open to the exterior via a single portal).
2. An intermediate sleeve of dry osmotic energy
source(sodium chloride).
3. The outer most rigid , rate controlling semi
permeable membrane fabricated from substituted
cellulosic polymers.
EXAMPLE : Ionized drugs , macromolecules ,
steroids and peptides.

26.  A rigid polymeric plug is used to form a leak proof
seal between the drug reservoir and the semi
permeable housing.
 An additional component , the flow modulator
,comprising of a cap and a tube made of stainless
steel is inserted into the body of osmotic pump after
filling.
 After implantation water from the surrounding tissue
fluids is imbibed through the semi permeable
membrane at a controlled rate that dissolves the
osmogent creating an osmotic pressure differential
across the membrane.
 The osmotic sleeve thus expands and since the outer
wall is rigid it squeezes the inner flexible drug
reservoir and the drug solution is expelled in a
constant volume per unit time.

27. DUROS INFUSION IMPLANT
 The duros osmotic implant is a non-biodegradable ,
miniature titanium cylinder intended to enable
systemic or tissue specific therapy for small
molecule drugs , peptides, proteins, DNA and other
bioactive molecules.
 The implant which is inserted subcutaneously and
retrieved at the end of the treatment duration is
designed to precisely and the continuously deliver
drugs for periods ranging from one month to more
than a year.
EXAMPLE :Leuprolide acetate implant.

28.  In a DUROS system , a protein or peptide is
formulated into a stable solution or suspension
which is protected by the water resistant , non
erodible , ,sterilized drug reservoir .

29.  The outer titanium alloy cylinder is capped by a
semi-permeable membrane at one end and by an exit
port at the other end.
 Within the DUROS system is implanted in the
human body , water from surrounding tissue enters
one end of the cylinder through the semi permeable
membrane causing the osmotic engine to swell.
 This osmotic engine displaces a piston which in turn
causes the drug formulation to be released from a
port at the other end of the system.

30. VAPOUR PRESSURE POWRERED
PUMP
 This device is based on the principle that at a given
temperature a liquid in equilibrium with its vapour
phase exerts a constant pressure that is independent
of enclosing pump.

31.  The disc shaped devices consists of two chambers.
 An infusate chamber containing the drug solution
which is separated by a freely movable flexible
bellow from the vapor chamber containing
inexhaustible vaporizable fluid such as flurocarbons.
 After implantation the volatile liquid vaporizes at
the body temperature and creates a vapor pressure
that compresses the bellows and expels the infusate
through a series of flow regulators at a constant rate.
EXAMPLE: Insulin for diabetics
Morphine.

32. BATTERY POWERED PUMPS
 Two types of battery powered implantable
programmable pumps used to deliver insulin are
PERISTALTIC PUMP AND SOLENOID DRIVEN
RECIPROCATING PUMP.
 Both with electronic controls.
 The systems can be programmed to deliver the drug
at desired rates.
 Their design is such that the drug moves towards the
exit and there is no backflow of infusate.

33. REFERENCES
 WWW.SYSREVPHARM .ORG
 NOVEL DRUG DELIVERY EDITED BY
W.CHEIN.