Advanced drug formation: Implants Flashcards
What are the types of advanced drug technologies
- Rate controlled
- Targeted
Advantages of controlled release vs conventional
-Less doses
>Less risk of overdose
Factors to consider when making sustained drugs
- Convenience and compliance
- Efficacy and safety
- Protection of franchises
- Adding value to generics
- Market expansion
- Creating new market
Convenience and compliance
- Slower release = less administration = better compliance
- Patient will prefer it in asymptomatic conditions such as hypertension
Efficacy and safety
Short half-life so sustained release is preferred
Protection of franchise
Patent on drugs expires in 20 years, after that any manufacture can produce that drug
Adding value to Generics
When original patent is expired and can be sold at low prices.
Advanced technologies applied to generic to differentiate from other companies.
Market expansion
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
Creating new market
Gene therapy
List the different types of drug release and their definitions
- 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
Types of implants and depots available
Non-degradable: Reservoir/matrix and solution and pore diffusion
Biodegradable: PLGA, Polyanhydrides and natural polymers
Pumps: osmotic and mechanical
Advantages of rate controlling implants/depots
Convenience and compliance
Flexibility in dosage rate
No first pass or enzymatic metabolism
Commercially convenient
Disadvantages of implants/depot
Invasive
Termination
Disadvantages of implants/depot
Invasive
Termination
Failure
Limited loading
Biocompatibility issue
commercially expensive
Types of Non-degradable implants
Reservoir device: Drugs is surrounded by rate controlled polymer membrane
Matrix device: Drug is distributed throughout continuous phase composed if polymer or liquid
What is Fick’s first law and what is the equation
It is the rate that a substance diffuses across a unit area.
dm/dt = Dk/h x A x Conc. gradient
What is Fick’s first law and what is the equation.
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
what is the limiting factor of a reservoir device
The memebrance
What is the release rate of a matrix system
Amount of drug is proportion to per unit area = partition coefficient x half life
( M=kt1/2)
What factors control the release of drugs in a matrix system
Initial conc. Porosity Tortuosity Polymer employed Solubility of drug
Limiting factor of the matrix device
The diffusion pathway
Examples of an implants includes
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
Limitations of non-degradable implants
- Surgically removed
- Application limited to neutral and hydrophobic molecules
- Limited control over release
- depends on characteristics of the polymer
what is the degradation mechanism of biodegradable implants
Bio-erosion
Biodegradation
What are the degradation patterns for the polymers
- Bulk erosion: whole polymer subject to degradation
- Surface erosion: limited to the surface
polymers use for biodegradable implants
Poly-lactide and poly-lactide-co-glycolide polymers (PLGA)
Lactid acid rich polymers are more stable against degradation
what are the stages of polymer degradations
- Polymer hydration
- Rupture of ester linkages
- Loss of mass, small parts become soluble and are absorbed
- Phagocytosis of polymeric segments
examples of biodegradable implants
-Zoladex: treat sex-hormones responsive tumours and endometriosis
What matrix is used for Zoladex
Goserelon acetate dispersed in a bulk-eroding PLGA matrix
What are the 2 combinations systems for dissolution-diffusion available
Swelling system: polymer absorbs water which dissolves the drugs
Biodegradable system: `dissolution of the polymer occurs in 2 different patterns
-Bulk erosion
-Surface erosion
Examples of pumps
Duros (Alza)
Alzet minipumps
Synchromed pumps
MidiMed pumps
