Advanced drug formation: Implants

Question 1

What are the types of advanced drug technologies

Answer 1

• Rate controlled

- Targeted

Question 2

Advantages of controlled release vs conventional

Answer 2

-Less doses

>Less risk of overdose

Question 3

Factors to consider when making sustained drugs

Answer 3

1. Convenience and compliance
2. Efficacy and safety
3. Protection of franchises
4. Adding value to generics
5. Market expansion
6. Creating new market

Question 4

Convenience and compliance

Answer 4

• Slower release = less administration = better compliance

- Patient will prefer it in asymptomatic conditions such as hypertension

Question 5

Efficacy and safety

Answer 5

Short half-life so sustained release is preferred

Question 6

Protection of franchise

Answer 6

Patent on drugs expires in 20 years, after that any manufacture can produce that drug

Question 7

Adding value to Generics

Answer 7

When original patent is expired and can be sold at low prices.

Advanced technologies applied to generic to differentiate from other companies.

Question 8

Market expansion

Answer 8

Advanced tech can make it possible to administer drug via different routes.

Self-administration increases population that can benefit from the drug and so increases the market

Question 9

Creating new market

Answer 9

Gene therapy

Question 10

List the different types of drug release and their definitions

Answer 10

• Delayed release: Release doesn’t start immediately
• Repeat action: More that one dose released
• Prolonged release: slow onset and slow release
• Sustained release: Initial release plus gradual release
• Rate-controlled release: drug release at controlled rate
• Target drug delivery: drug released in specific location

Question 11

Types of implants and depots available

Answer 11

Non-degradable: Reservoir/matrix and solution and pore diffusion

Biodegradable: PLGA, Polyanhydrides and natural polymers

Pumps: osmotic and mechanical

Question 12

Advantages of rate controlling implants/depots

Answer 12

Convenience and compliance

Flexibility in dosage rate

No first pass or enzymatic metabolism

Commercially convenient

Question 13

Disadvantages of implants/depot

Answer 13

Invasive

Termination

Question 14

Disadvantages of implants/depot

Answer 14

Invasive

Termination

Failure

Limited loading

Biocompatibility issue

commercially expensive

Question 15

Types of Non-degradable implants

Answer 15

Reservoir device: Drugs is surrounded by rate controlled polymer membrane

Matrix device: Drug is distributed throughout continuous phase composed if polymer or liquid

Question 16

What is Fick’s first law and what is the equation

Answer 16

It is the rate that a substance diffuses across a unit area.

dm/dt = Dk/h x A x Conc. gradient

Question 16

What is Fick’s first law and what is the equation.

Answer 16

It is the rate that a substance diffuses across a unit area. Used in a reservoir system

dm/dt = Dk/h x A x Conc. gradient

• D= diffusion coefficient
• k= partition coefficient
• h= thickness of membrane
• A= surface area

Question 17

what is the limiting factor of a reservoir device

Answer 17

The memebrance

Question 18

What is the release rate of a matrix system

Answer 18

Amount of drug is proportion to per unit area = partition coefficient x half life
( M=kt1/2)

Question 19

What factors control the release of drugs in a matrix system

Answer 19

Initial conc.
Porosity
Tortuosity
Polymer employed 
Solubility of drug

Question 20

Limiting factor of the matrix device

Answer 20

The diffusion pathway

Question 21

Examples of an implants includes

Answer 21

Norplant: Subdermal implant contraceptive (levonorgestrel 30micrograms/day)
-silicone rubber membrane
Implanon: Subdermal implant of etonogestrel 40 micrograms/day
-Hybrid system: Matrix Core: EVA (28% vinyl acetate) more polar less affinity
Membrane: EVA (14% vinyl acetate) rate limiting diffusion step

Question 22

Limitations of non-degradable implants

Answer 22

• Surgically removed
• Application limited to neutral and hydrophobic molecules
• Limited control over release
  
  • depends on characteristics of the polymer

Question 23

what is the degradation mechanism of biodegradable implants

Answer 23

Bio-erosion

Biodegradation

Question 24

What are the degradation patterns for the polymers

Answer 24

• Bulk erosion: whole polymer subject to degradation

- Surface erosion: limited to the surface

Question 25

polymers use for biodegradable implants

Answer 25

Poly-lactide and poly-lactide-co-glycolide polymers (PLGA)

Lactid acid rich polymers are more stable against degradation

Question 26

what are the stages of polymer degradations

Answer 26

• Polymer hydration
• Rupture of ester linkages
• Loss of mass, small parts become soluble and are absorbed
• Phagocytosis of polymeric segments

Question 27

examples of biodegradable implants

Answer 27

-Zoladex: treat sex-hormones responsive tumours and endometriosis

Question 28

What matrix is used for Zoladex

Answer 28

Goserelon acetate dispersed in a bulk-eroding PLGA matrix

Question 29

What are the 2 combinations systems for dissolution-diffusion available

Answer 29

Swelling system: polymer absorbs water which dissolves the drugs
Biodegradable system: `dissolution of the polymer occurs in 2 different patterns
-Bulk erosion
-Surface erosion

Question 30

Examples of pumps

Answer 30

Duros (Alza)

Alzet minipumps

Synchromed pumps

MidiMed pumps