Module 2C Implantable Systems

Question 0

Define: biocompatibility

Answer 0

How well the body responds to a foreign material. So that it doesn’t injure or cause toxic or immunological responses in living tissue.

Question 1

Define: implant

Answer 1

A single unit drug delivery system that has been designed to deliver a drug at a desired rate over a prolonged period of time.

Rate control forms an intrinsic part of implantable systems
Require specialised administration
Usually subcutaneously
-arm
-thigh
-lower section of the abdomen
-also in the vitreous cavity of the eye

Question 2

Define: monolithic dispersion

Answer 2

The drug is present above the saturation level, additional drug exists as dispersed particles in the polymer matrix.

Question 3

Define: reservoir-type non-degradable polymeric implant

Answer 3

Is a type of non-degradable polymeric implant.
Reservoir devices; the drug is surrounded by a rate-controlling polymer membrane.
-solution diffusion: non-porous barrier water penetrates into the
implant allowing drug release via diffusion.
-pore-diffusion: the rate controlling membrane is porous

Drug release is governed by diffusion- must diffuse through the polymer membrane in order to be released

Question 4

Define: matrix-type non-degradable polymeric implant

Answer 4

A type of non-degradable polymeric implant
Matrix devices; in which the drug is distributed throughout the polymer matrix.

Drug release is governed by diffusion- must diffuse through the polymeric matrix in order to be released

Question 5

Define: bioerosion and biodegradation as they relate to biodegradable polymeric implants

Answer 5

Degradation can take place via one of the following mechanisms;
1. Bio erosion- gradual dissolution of a polymer matrix
2. Biodegradation- degradation of the polymer by chemical or
enzymatic processes -> toxicity

Question 6

Define: bioresponsive implantable system

Answer 6

A feedback regulated system that releases drug in response to stimuli
Eg: glucose-triggered insulin system

Question 7

Advantages of implants as drug delivery systems

Answer 7

1. Convenience
2. Compliance
3. Controlled release
4. Intermittent release
5. Bio-responsive release
6. Improved drug delivery
7. Flexibility
8. Commercial advantages

Question 8

Disadvantages of implants as drug discovery systems (7)

Answer 8

1. Invasive
2. Termination (non-biodegradable: surgically retrieved at end of
   treatment. Biodegradable: difficult to terminate drug
   delivery and difficult to maintain dose at the end of its
   lifetime.)
3. Danger of device failure (surgical intervention to fix)
4. Limited to potent drugs (small implant -> high concentration of drug)
5. Adverse reactions
6. Biocompatibility issues
7. Commercial disadvantages (cost to develop, regulations)

Question 9

Detail the potential sources of short and long term toxicity of implants (4)

Answer 9

1. The intact polymer
2. Residual contaminants: filler products
3. Toxic degradation products: formaldehyde, liver toxins
4. Polymer/tissue interfacial properties: encapsulation of implant by
   fibrous tissue

Question 10

What is the difference between solution diffusion and pore diffusion in reservoir-type non-degradable polymeric implants (4)

Answer 10

Solution diffusion:
Is bound by a nonporous rate controlling polymeric membrane.
The penetration of a solvent (water) initiates drug relies via passive diffusion.
Eg: silicones, polyethylene

Pore diffusion:
Membrane is not compact but it is porous.
Drug molecules are released by diffusion through micropores that are filled with water or oil. Selection of solvent is very important as it affects drug permeability and solubility.

Question 11

What are the limitations of non-biodegradable implants (4)

Answer 11

1. Surgically inserted and removed
2. Poor diffusion through hydrophobic membranes
3. Difficult to achieve specific rates

Question 12

How has implantable gel technology been utilised in natural biodegradable polymeric implants. Refer to specific commercial product to illustrate answer. (4)

Answer 12

The drug is incorporated within the mesh work of rod shaped collagen molecules. The collagen matrix is then converted to an injectable gel by a chemical modifier.
Eg: direct injection of gels into solid tumours. Drug retention at the site is achieved by vasoconstrictors (adrenalin). Injectable gel products:
- Intradose (cysplatin/adrenalin): treatment for solid
tumours
- Advasite (flurouracil/adrenalin): treatment of external warts, basal cell carcinoma, squamous cell carcinoma, psoriasis.

Question 13

Describe the essential device design/technology employed in implantable pumps (4)

Answer 13

Implantable pumps:
Drug release is achieved by a pressure difference that causes the bulk flow of the drug from the pump at a controlled rate.
This is in contrast to the polymeric controlled release systems that use diffusion to distribute the drug.
Pressure differences in implantable pumps can be created by:
1. Osmotic action (osmotic implantable pumps)
2. Mechanical action (mechanical implantable pumps)
1. Osmotic implantable pumps:
Water moves through semi-permeable membrane causes the osmotic chamber to expand. This force compresses the flexible drug reservoir discharging the drug solution.

2. Mechanical implantable pumps:
   Are implanted peritoneally in a pocket created in the abdominal wall. Under fat layers but above muscle. Sutured into muscle fascia.
   Eg: insulin pump