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1. Introduction of implants. 2. Inserts 3. Ideal properties. 4. Advantages. 5. Disadvantages. 6. Mechanism of drug release. 7. Application.

In 1861, Lafarge INTRODUCED the concept of implantable system for sustained drug administration . Used to produce slolid implants containing steroid hormones inititating the use of implantable system for long term delivery. Implantable drug delivery systems are placed completely under the skin and designed to release drugs into the bloodstream without the repeated insertion of needles. Well suited to the drug delivery requirements of insulin, steroids, antibiotics, analgesics, parentral nutrition and heparin.

These devices are prepared from solid and semisolid consistency which are inserted into the body. Can be shaped according to the need. Examples opthalmic inserts ,intravaginal inserts and intra uterine devices (IUDS).

Ideal requirements of implantable drug delivery systems. 1.Environmentally stable. 2.Biocompatible. 3.Easy to Sterilize. 4. Rate controlled release of drug. 5.Improve patient compliance by reducing the frequency of drug administration over the entire period of treatment. 6.Release the drug in a rate-controlled manner that leads to enhanced effectiveness and reduction in side effects. 7.Readily retrievable by medical personnel to terminate medication. 8.Easy to manufacture and relatively inexpensive. 9.Good mechanical strength. 10. Free from surgical procedure.

1.Convenience:-implantation therapy permits patients to receive hospital with minimal medical surveillance. medication outside the

2. Compliance:-improve patient compliance especially in old age patients. Effective drug concentrations in the bloodstream can be maintained for long periods in patients . No need to take medication at regular interval of time.

3. Potential for controlled release:Implants are available which deliver drugs by zero-order controlled release kinetics. Zero order controlled release offers the advantages (a) Avoiding the peaks (risk of toxicity) and troughs (risk of ineffectiveness) of conventional therapy. (b) Reducing the dosing frequency.

4. Potential for intermittent release :Externally programmable pumps can facilitate intermittent release useful in (a) Fluctuating metabolic needs; (b) The pulsatile release of many peptides and proteins.

5. Improved drug delivery:-Using an implant system the drug is delivered locally or in systemic circulation with minimal interference by biological or metabolic barriers.

6. Flexibility:-Considerable flexibility is possible with these systems, in the choice of materials, methods of manufacture, degree of drug loading, drug release rate etc.

1.Invasive:-Either a minor or a major surgical procedure is required to initiate therapy.

2. Termination:-Non-biodegradable polymeric implants and osmotic pumps also be surgically retrieved at the end of treatment.

3. Danger of device failure:-the device may for some reason fail to operate. which again requires surgical intervention to correct.

4. Possibility of adverse reactions: - local high drug concentration may trigger adverse reactions.

5. Biocompatibility issues:-responses to a foreign material often raise the issues of biocompatibility and safety of an implant.

6. Commercial disadvantages:-Developing an implantable drug delivery system requires an enormous amount of R&D investment in terms of cost, effort and time .


Mechanism of drug release from various implantable drug delivery systems :1. Diffusion controlled. a) Membrane-permeation controlled. b) Matrix-controlled. c) Micro reservoir-dissolution controlled. 2.Chemically controlled. a) Bioerosion-controlled . b) Pendent chain controlled. 3. Swelling controlled. 4. Osmotically controlled. 5. Magnetically controlled


These devices are based on Flicks law of diffusion which states the rate of transfer of a diffusing substance through unit area of a section. In this case the rate of release is controlled by diffusion of drug through a polymeric membrane. Diffusion-controlled drug delivery system work best for drugs with molecular weight of 1000 Daltons or less. Rate of drug release depends on the pore size of the membrane. a) Membrane-permeation controlled : In membrane-permeation controlled devices the drug reservoir is surrounded by a membrane (coating). Because of the presence of the two distinct drug-reservoir and membrane phases these are known as heterogen Mechanism of drug release : When the device containing a highly hydrophilic drug is placed in the aqueous dissolution medium water penetrates the coating and dissolves the drug and the concentrated drug solution diffuses out through the polymeric membrane. The release rate of the drug is controlled by the diffusion rate of drug solution through the polymeric membrane. Examples : 1.Ocusert an ocular insert for controlled pilocarpine release for the treatment of glaucoma. 2. Progestasert, a T-shaped contraceptive intrauterine device the controlled progesterone release. 3. Norplant which is comprised of six small injectable cylinders for controlled release of levonorgestrone for contraception.


b) Matrix-controlled In matrix-controlled devices the drug is uniformly distributed (dissolved of dispersed) throughout the polymer and hence these are known as homogeneous devices. Mechanism of drug release: In the presence of dissolution medium drug at the surface dissolves first and is released in the dissolution medium. In many cases the dissolved drug creates a depletion boundary separating the empty or drug-depleted polymer from the drug-loaded polymer matrix. Water penetrates the channels or pore created by drug depletion and dissolves the drug at the depletion boundary. The drug release rate is controlled by the diffusivity barrier provided by the empty matrix which increases in thickness with time.

c) Micro reservoir-dissolution controlled In these devices the drug reservoir is made of a suspension of solid drug particles in an aqueous solution of a water miscible polymer forming millions of microscopic drug reservoirs in a polymer matrix. the device is coated with a rate-controlling membrane to further modify the drug release rate. Among the other factors the release rate is dependent on the solubility of drug in the liquid compartment and on the polymer matrix. Example:- Syncro-Mate-M implant. It is a cylindrical implant fabricated by dispersing the drug reservoir (a suspension of norgestomer in an aqueous solution of PEG 400) in silicone elastomers. This device is implanted subcutaneously in he earflap of livestock for about 20 days delivery of norgestomet for control and synchronization of estrus and ovulation.

2.Chemically controlled
Chemically controlled drug delivery systems regulate the drug release rate by a chemical reaction with the polymer. Principle Advantage:The polymer is dissolved and absorbed by the body and there is no need for surgical removal of the device at the completion of drug delivery. Types:-

a) Bioerosion-controlled . b) Pendent chain controlled.

a) Bioerosion-controlled Bioerosion-controlled devices are matrix controlled with uniform drug distribution inside the polymer. Mechanism of drug release: The bioerosion or biodegradation systems involve breakdown of the polymer into small water-soluble molecules. As the polymer is broken down water comes in contact with the drug leading to its dissolution and release. Advantage:-

An important advantage of this type of system is that the drug-release profile may be controlled by manipulation of the size and shape of the device, amount of drug loading in addition of other excipients and the intrinsic degradation rate and molecular weight of the polymer.


b) Pendent chain controlled The other mechanism for chemically controlled release of drug is known as the pendentchain system where the drug is attached to the polymer backbone by a labile chemical linkage. Mechanism of drug release: In the presence of water or enzymes the labile linkage breaks to release the drug. A water-soluble backbone may serve as a drug carrier to a specific cell or organ where the drug is released by metabolism. Insoluble pendent chains on the other hand serve as a depot from which the drug is slowly released. Advantage:-

Varying the hydrophilicity of the polymer backbone and the device geometry can control the rate of linkage degradation and therefore the drug release.

3. Swelling controlled.
Swelling-controlled systems are similar to matrix-type devices except that the dispersed drug is immobilized inside a glassy polymer and therefore there is no diffusion of drug. Mechanism of drug release: When this device is placed in water the outer polymer region begins to swell, resulting in relaxation of the polymer chains. This allows the otherwise locked drug to diffuse outward. The drug release is determined by the rate of relaxation of the chains that unlock the drug.

4.Osmotically controlled
Osmotically controlled systems provide a predictable, zero-order release rate independent of the physicochemical properties of the drug . Mechanism of drug release: In an osmotically controlled system an osmotically active agent such as water-soluble salt is placed inside a rigid semi permeable polymer housing, which is separated from the drug compartment by a movable partition. The semi permeable housing draws water inside by osmosis, leading to an increase in volume and exertion of pressure on the movable partition.

The partition, in turn pushes the drug out of the compartment through a delivery orifice or cannula. Examples :1.Alzet osmotic pumps. 2. The OROS system is being used for oral delivery of drugs such as phenylpropanolamine.

5.Magnetically controlled
In magnetically controlled drug-delivery systems the drug and magnetic beads are uniformly dispersed inside semi elastic polymer matrix made of a nonbiodegradable polymer such as ethylene-vinyl acetate copolymer. Mechanism of drug release: When the device is placed in a magnetic field, the magnetic beads tend to oscillate compressing and expanding the polymer in the process. This is proposed to result in a pulsatile flow of the dissolution medium through the pores in the elastic polymer and along the concentration gradient of the drug resulting in an increase in the drug-release rate.

Fig :- Magnetically Controlled System

1.Ocular disease:a) Ocusert containing pilocarpine base and alginic acid in a drug reservoir surrounded by a release-rate controlling ethylene-vinyl acetate membrane used in glaucoma. b) Implantable devices evaluated for ocular cancer treatment include silicone rubber balloon containing an antineoplastic agent( BCNU). 2. Contraception:a) Norplant a subdermal implant for long-term delivery of the contraceptive agent levonorgestrel b) The progestasert an ethylenevinyl acetate copolymer intrauterine drug-releasing device. 3. Dental application:a)For sustained-release fluoride delivery stannous fluoride was incorporated into different dental cements. b) Ethycellulose slabs containing polyethylene glycol and chlorhexidine as an antibacterial agent. c) Hollow gibers containing 20% solution of chlorhexidine gluconate and placed in periodontal pockets resulted in significant clinical improvement with relief of discomfort, reduced gingival flow, and less bleeding on probe. 4. Immunization:Polymeric implants are being evaluated for enhanced immune response to antigens. For exWise et al. evaluated immunization efficacy of ethylene-vinyl acetate copolymer pellets containing bovine serum albumin as model antigen.

5. Cancer :-

a) Silicone rod implants similar to those used for delivery of levonorgestrone have been evaluated for delivery of testosterone propionate or ethinyl estradiol in patients with prostate cancer. b) Lupron depot manufactured by Takeda chemical industries is an implantation system providing one month depot release of leuprolide acetate. a synthetic analogue of the gonadotropin-releasing hormone(GhRH) for the treatment of prostate cancer . c) Zoladex manufactured buy ICI Pharma provides one month depot release of goserelin acetate from a biodegradable implantable rod for the treatment of prostate cancer. 6. Narcotic antagonists :Naltrexone has been extensively evaluated in implant from long- term delivery of narcotic antagonists. 7.Diabetes :Numerous insulin - delivery implant systems have been prepared and evaluated