Implants

Implants:Definition: A sterile drug delivery device for subcutaneous

implantation having the ability to deliver drug at a controlled rate over a prolonged period of time, comprising a rod shaped polymeric inner matrix with an elongated body and two ends.

Implants :Advantages: Controlled drug delivery for over a long time

(months/years) Improve patient compliance Targeted drug delivery Decrease side effects Improve availability of drugs

Disadvantages:- Mini-surgery is needed- Uneasy to simply discontinue the therapy- Local reactions

Drug Release Mechanisms: Diffusion controlled devices Solvent controlled devices

Erodible devices

Regulated release They are devices with externally-applied trigger to turn release

on/off

i. electrical

ii. mechanical

Diffusion Controlled Devices:

There are two types of diffusion controlled systems: A- Matrix devices- The drug is either dissolved or dispersed in the polymer. The

drug is released from the matrix by diffusion (no membrane).

Diffusion Controlled Devices:

Advantages:

Simple and convenient to prepare.

Drug dumping is not a problem.

Disadvantages:

i. Release rate decreases with time.

ii. If implanted and matrix is nondegradable (silicon, rubber), may need to retrieve after delivery is finished.

Diffusion Controlled Devices:

B- Reservoir devices - Consist of a drug core which can be in powdered or liquid form.

The drug core is surrounded by a non-biodegradable polymeric material which the drug slowly diffuses through.

Disadvantages

i. Non degradable implants

ii. Diffusion of large molecules such as proteins through the polymer is too slow to be effective

iii. Danger of ‘dose dumping’ in barrier systems if membrane is ruptured

Advantages

Constant release rate with time

Diffusion Controlled Devices:

Solvent Controlled Devices:

Solvent controlled release devices are a result of solvent penetration.

There are two types of solvent controlled systems: A- Osmotic Osmotic controlled systems involve an external fluid moving

across a semi-permeable membrane into a region within the device containing a high concentration of drug. The increased volume in the osmotic compartment forces the drug out through a small orifice.

Non-bioerodible dosage form

Solvent Controlled Devices:

Osmosis is the movement of a solvent through a semi-permeable membrane from a region of low-solute concentration to a region of high-solute concentration.

Solvent Controlled Devices:

When implanted, a large, constant osmotic gradient is established between the tissue water and the osmotic engine which provides a region of high NaCl concentration.

In response to the osmotic gradient, water is drawn across the membrane into the osmotic engine.

The water imbibed into the osmotic engine expands its

volume, thereby displacing the piston at a controlled, steady rate.

This displacement pumps drug formulation from the drug reservoir through the exit port and into the patient.

Solvent Controlled Devices: The system consists of an outer cylindrical titanium alloy

reservoir which protects the drug molecules from enzymes, body moisture, and cellular components.

At one end of the reservoir is positioned the membrane, from a polyurethane polymer. The membrane is permeable to water but impermeable to ions.

Positioned next to the membrane is the osmotic engine. Next to the engine is the piston. The piston is made from

elastomeric materials and serves to separate the osmotic engine from the drug formulation (may be either a solution or suspension).

At the distal end of the titanium cylinder is the exit port. Radiation sterilization (gamma) may be utilized to sterilize

the final drug product.

Solvent Controlled Devices:

Viadur implant delivers leuprolide for the treatment of prostate cancer

Solvent Controlled Devices: 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.

Solvent Controlled Devices:B- Swelling In swelling controlled systems, a polymer which can hold a

large volume of water is employed. When the device is placed in an aqueous environment water penetrates the matrix and the polymer consequently swells and the drug is able to diffuse through.

It is nondegradable.

Erodible devices: Combination of polymer breakdown and drug diffusion

through matrix.

Advantage: Being injectable and resorbable(no retrieval surgery)

Disadvantage: Therapy difficult to stop once injected due to difficult recovery of particles

Example: Lupron depot

One month injectable implant containing leuprolide acetate for treatment of endometriosis and prostatic cancer.

Erodible devices: NALTREXONE PELLETS Naltrexone pellets block the effects of heroin and other

opiates when inserted under the skin. They gradually release their medication over time.

500 mg naltrexone pellets that are replaced every two months, and 800 mg naltrexone pellets that are replaced every three months

DISULFIRAM PELLETS Treat alcoholism

Electrical regulated release:

Concept

Store drugs in micro-fabricated implants and release them on command Advantages

•Protects drugs until release

•Controls the following parameters using

microprocessors:

–Time

–Rate

–Drug combinations

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

Electrical regulated release: E.g. Silicon Microchip Contained an array of

reservoirs etched in silicon. The reservoirs were capped with gold membranes (anode) that could be electrochemically dissolved in tissue 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.

Electrical regulated release:

Micrographs of gold membranes (a) before and (b) after electrochemical dissolution

Electrical regulated release:

The electrothermal mechanism soon supplanted the electrochemical mechanism at MicroCHIPS for several reasons:

1- Faster operation

2- Independence of the membrane material and surrounding environment

Here we replace gold with another

metal that can be melted by heat