A re-edited and corrected note on types of Implants used in Pharm. Industry. Focussed and to the point.

1. Workedby: Ashani B (Realignedby SurajC)
Development and evaluation of implantable drug delivery system
(ADDS)
 INTRODUCTION:
 In the year 1861, Lafarge introduced the concept of implantable system for sustained
release drug administration.
 In the very beginning it was first introduced to produce the solid implants containing
steroid hormones implantable system for long term delivery.
 Implantable drug delivery systems are placed under the skin and designed to release drugs
into the bloodstream without the repeat insertion of needles.
 Therefore as for the definition,
o “A sterile drug delivery device for subcutaneous implantation having the ability to deliver
the drugs at a controlled rate over a prolonged period of time, comprising a rod shaped
polymeric inner matrix with an elongated body and two ends.”
 Ideal properties of an implantable drug delivery system:
I. Environmentally stable.
II. Biocompatible
III. Easy to sterilize.
IV. Rate controlled release of drug.
V. Improve patient compliance by reducing the frequency of the drug
administration over the entire period of treatment.
VI. Easy to manufacture & relatively inexpensive.
VII. Good mechanical strength.
VIII. Free from surgical procedure.
 ADVANTAGES:
 Convenience: Implantation therapy permits patients to receive medication outside
the hospital with minimal medical surveillance
 Compliance: Compliance is increased greatly by allowing a reduction or complete
elimination of patient involved dosing.
 Improved drug delivery: Using an implantable drug delivery system the drug is
delivered locally or systemic circulation with minimal interference by biological or
metabolic barriers.
 Potential for controlled release: These deliver drugs by zero order controlled
release kinetics, so it can reduce the dosage frequency and increase the patient
compliance.

2. Workedby: Ashani B (Realignedby SurajC)
 Potential for intermittent release: Extremely programmable pumps can facilitate
intermittent release in response to various factors such as cardiac rythm, metabolic
needs etc.
 Flexibility: Various types of flexibilities like materials, method of manufactures
etc. are available in case of implants. Controlled delivery of both hydrophilic and
lypophillic drugs can be obtained from here.
 DISADVANTAGES:
 Invasive: For the insertion of the implants patient has to face either a major or a
minor surgical procedure.
 Termination: non-biodegradable polymeric implants can be terminated from the
body also with the help of a surgical method at the end of the treatment.
 Danger of device failure: If due to some reason the device fails to operate
properly during the treatment then again surgical steps should be taken for removal
of the device from the patient’s body.
 Limited to potent drug: The size of the device is very small to reduce the
patient’s discomfort, therefore only the potent drugs which are very small in
amount can only be used in this system.
 Adverse reaction: As a high concentration of drug is delivered to the implantation
site with the help of the device therefore there is always a chance of adverse
reaction due to this local high concentration.
 MECHANISM of drug release from implantable therapeutic system:
 Over the years a large number of mechanisms have been derived to obtain the controlled
release delivery of drug for a prolonged time with the help of implantable drugs. Now
these approaches are designed as follows;
 Given chart………………….. at the end of paper

3. Workedby: Ashani B (Realignedby SurajC)
A. Polymer membrane permeation controlled drug delivery system:
 In this controlled drug delivery device, drug reservoir is totally encapsulated within a capsule
shaped or spherical compartment.
 This total system is covered with a rate controlling polymeric membrane.
 The drug reservoir can be either solid particles or the dispersion of the solid particles in a liquid
or solid dispersing medium.
 The encapsulation of the drug reservoir system inside the polymeric membrane can be done by
the encapsulation, microencapsulation, molding, extrusion etc.
Example: Norplant subdermal implant.
Pic 1: Implantation of 6 units of norplant subdermal implant in the subcutaneous tissue of a
human subject’s arm
B. Polymer matrix diffusion controlled drug delivery system:
 In this implantable device the reservoir is formed by dispersion of the solid particles throughout
a lipophilic or hydrophilic polymer matrix.
 This dispersion can be obtained by dispersing the solid drug dosage form in the liquid or semi-
solid polymer matrix at the room temperature followed by cross linking of the polymer chains.
 The drug polymer dispersions are then molded or extruded to form drug delivery devices of
various shapes.
 It can also be prepared by dissolving the drug solid or the polymer in an organic solvent followed
by conservation or solid evaporation at an elevated temperature under a vacuum to form
microsphere.
Example: Compudose implant.

4. Workedby: Ashani B (Realignedby SurajC)
C. Membrane-matrix hybrid type drug delivery system
 This type drug delivery system is actually a hybrid form of polymer membrane permeation
controlled drug delivery system and the polymer matrix permeation controlled drug delivery
system.
 It follows the constant drug release kinetics just like the polymer membrane permeation
controlled drug delivery system.
 Therefore it will reduce the chances of dose dumping from the reservoir compartment.
 Just like the matrix diffusion system the drug reservoir is also prepared by the homogenious
dispersion of the drug solid particles throughout a polymer matrix.
 But in case of this implantable drug delivery, the total reservoir is encapsulated within a rate
controlling polymeric membrane.
 This is actually a sandwich type implantable device.
Example: Norplant II subdermal implant.
D. Microreservoir partition controlled drug delivery system
 In this controlled release drug delivery device the drug reservoir is a suspension of drug crystals
in an aqueous solution of water miscible polymer & it also forms a homogeneous dispersion.
 Microdispersion is obtained by the high energy dispersion technique.
 Different size and shapes of drug delivery devices can be obtained with the help of extrusion and
molding.
 According to the physicochemical properties of the drug, the device can be further coated with a
layer of biocompatible polymer to modify the mechanism & the rate of drug release.
Example: Syncromate implant.
Pic 2: The compudose implant
Pic 3: The norplant II subdermal
implant

5. Workedby: Ashani B (Realignedby SurajC)
Pic 4: photomicrograph of a microreservoir type drug delivery system that shows the
microscopic structure of various components
E. Osmotic pressure activated drug delivery system
 From the abovementioned definition it can be easily assumed that the osmotic pressure is the
main source of energy in this case to activate and modulate the delivery of drug.
 In here, the drug reservoir is either a solution or a semisolid state which is contained within a
semipermeable compartment with controlled water permeability.
 The volume of the drug solution released is determined by the equation;
Example: Alzet osmotic pump.
Pic 5: Alzet osmotic pump
Polymermatrix
Drug reservoir
Coating
membrane
Polymer/
surface interface

6. Workedby: Ashani B (Realignedby SurajC)
F. Vapour pressure activated drug delivery system
 In this drug delivery device the vapour pressure is mainly used as the power source to activate
the controlled delivery of drugs.
 The drug reservoir contains a solution.
 The reservoir stays inside an infusate chamber.
 Infusate chamber is physically separated from the vapour pressure chamber by freely movable
bellows.
 Vapour pressure chamber contains a vaporizable fluid viz. Fluorocarbon. Fluorocarbon vaporizes
at body temperature and & creates the vapour pressure which will forcefully move the bellow in
upwards direction.
 Therefore the drug solution enters into the cannuals at a constant flow rate and we can calculate
the flow rate with the help of the equation;
G. Magnetically activated drug delivery system
 Electromagnetic energy is used as the power source to activate the drug delivery system and to
control the rate of drug delivery.
 A magnetic wave triggering mechanism is incorporated into the drug delivery device.
 A subdermally implantable, magnetically modulated hemispherical drug delivery device was
fabricated by positioning a tiny donut shaped magnet at the center of a polymer matrix.
 It contains a homogeneous dispersion of a drug with low polymer permeability at a rather high
drug-polymer ratio to form hemispherical pellet.
 The external surface of the hemispherical pellet is totally covered with a pure polymer, viz.
Ethylene vinyl acetate copolymer.
 By applying an external magnetic field the drugs are activated by the electromagnetic energy to
release from the pellet at a much higher rate of delivery.
Example: Bovin serum albumin (BSA) is generally given by the help of this device.
Pic 6: Magnetically activated drug
delivery system

7. Workedby: Ashani B (Realignedby SurajC)
H. Hydration activated drug delivery system
 This type of drug delivery device releases the drug molecules upon activation by hydration of the
drug delivery device by tissue fluid at the implantation site.
 This device is generally prepared from the hydrophilic polymer.
 Drug molecules are released by the diffusion through the water saturated pore channels in the
swollen polymer matrix.
Example: Norgestomet releasing hydron implant for estrus synchronization
in heifers.
 This subdermal implant is extremely small in size.
 It can be easily implanted into the animal’s ear flap (dorsal side).
 A specially designed implanter is generally used in this case.
Pic 7: Implanter with a unit of implant in position, designed specifically for the subcutaneous
implantation
I. Hydrolysis activated drug delivery device
 In here the drug delivery device is activated by the hydrolysis.
 This hydrolysis is generally happened on the polymer base by the application of the tissue fluid
at the implantation site.
 In here, the drug delivery device is fabricated by dispersing a loading dose of drugs in
micronized form.
 For this reason a biodegradable polymer is used and then it is molded into a pellet or bead
shaped implant.
 In this device the rate of drug release is determined by the rate of biodegradation, polymer
composition and molecular weight, drug loading and drug-polymer interaction.
 The rate of drug release is not constant and highly dependent upon the erosion process of the
polymer matrix.
Example: biodegradable naltrexone pellets fabricated from poly copolymer for the
antinarcotic treatment of opoid-dependent-addicts.
NOTE: Beside this several biodegradable or bioerodible polymers like polyglycolide,
polyanhydride etc. can also be used.

8. Workedby: Ashani B (Realignedby SurajC)
 APPLICATIONS
1. Biomedical application
i. An implantable drug delivery system offers a great advantage injectable controlled
release formulations.
ii. Parenteral controlled administration of drugs via subcutaneous or intramuscular drug
delivery device can gain easy access to the systemic circulation to achieve a total
bioavailability of drugs as well as a continuous delivery of drugs unlike transdermal, oral
etc. routes of administration.
2. Human application
i. For the past few years several types of implantable drug delivery systems have been
discovered with the aim to achieve continuous administration of systemically-active
drugs for the long term regulation of a physiological process.
ii. An example of human application is norplant subcutaneous contraceptive drug delivery
system.
iii. Due to the excellent results from the WHO sponsored clinical studies with the norplant,
another second generation of subcutaneous contraception which is also known as
the Norplant-II has been produced. According to the investigators, due to the easy
insertion and the removal procedure of the Norplant-II, it is much more preferable to the
patients rather than the Norplant-I system.
iv. A new generation of subcutaneous contraceptive implant, “Implanon” is recently
developed and it is also a sandwitch type implant device.
v. Continuous heparinization in anticoagulation treatment with the help of a infusaid pump
is also available today.
vi. Infusid pumps are also applied for the intravenous controlled infusion of insulin for the
continuous treatment of diabetis. A soluble insulin preparation is used as the drug
reservoir in this case.
vii. Nowadays several biodegradable subdermal implants has been made with the help of
biodegradable polymers.
viii. With the help of subcutaneous injections of goserelin in solution followed by
subcutaneous administration of the goserelin-releasing subdermal implalnt at three dose
levels clinical evaluation of the antitumor effect is also possible.
3. Veterinary application
i. Several implantable drug delivery devices have been prepared from biocompatible
polymers for veterinary application.

9. Workedby: Ashani B (Realignedby SurajC)
ii. A typical example is, Norgestomet releasing subdermal implants for estrus
synchronization.
iii. Also for the purpose of clinical evaluation.
4. Medical Aspects
i. Animal tissue contains approximately 70% of body fluid. There are many enzymes in our
body fluid. As there are many reactions which are dependent upon various trace metals,
therefore through investigation is needed to search for the long term effect of chemicals
or degradation of the implanted polymeric materials.
ii. Reactions of host to implant and vice-versa are also one of the important aspect in this
case.

10. Workedby: Ashani B (Realignedby SurajC)
Implantable drug
delivery system
Controlled drug
delivery by diffusion
process
A. Polymer membrane
permeation controlled
drug delivery system
microporous
membranes
Non porous
membrane
Semipermeable
membrane
Matrix diffusion
controlled drug
delivery system
Lipophillic polymers
hydrophilic polymers
porous polymers
Microreservoir
partition controlled
drug delivery system
Hydrophili reservoir in
lipophilic matrix
Lypophilic reservoir in
hydrophilic matrix
Membrane-matrix
hybrid type drug
delivery system
lipophilic membrane
with hydrophilic
matrix
hydrophilic
membrane with
lipophilic matrix
controlled drug
delivery by activation
process
osmotic pressure
activated
vapour pressure
activated
magnetically
activated
Hydrolisis activated
hydration activated
phonophoresis
activated
Controlled drug
delivery by feed-back
process
Bioerosion regulated
drug delivery
Bioresponsive drug
delivery