Lecture 21.5 - Polymeric Drug Delivery Devices Flashcards
Enteral
- Intestinal (process through)
- All other routes considered parenteral
Intravenous/Inraarterial
Parenteral
Intramuscular/Subcutaneous
Parenteral
Oral
Enteral
Buccal/Sublinqual
- On cheek/under tongue
- Enteral
Rectal
Enteral
Nasal
Enteral
Pulmonary
Parenteral
Vaginal
Enteral
Intrauterine
Enteral
Transdermal
Enteral
Oscular
Parenteral
Half Life
- Many drugs have very short half lives
- Ampicillin (100 min)
- Penicillin (45 min)
How to Maintain Drug Action?
- Requires significant concentration to remain effective
- Take repeated doses —> maintain activity by adding different doses of drug at different times
Controlled Drug Delivery
- Better targeting (spatial targeting, temporal targeting)
- Reduce discomfort to patient (constant injections)
- Ability to reposition drug on the market (using different delivery system)
- Long lasting therapeutics
- Direct cell function in healing or forming tissues
Spatial Targeting
Delivered to certain locations
Temporal Targeting
Delivered in certain concentration at certain times
Ideal Drug Delivery Systems
- Deliver drug at rate which matches need of body
- Deliver drug only to active site (cell, tissue, or organ)
- No drug delivery systems do both
Common Systems/Release Rates
- Systems which provide “some” control of drug release in body (temporal, spatial, partial control of both)
- Prolonged or sustained release in systems are not controlled release systems by this definition (not spatially targeting, burst release where released over time)
Sustain Drug Action
- Maintain constant effective drug level in body
- Avoid undesirable side effects of sawtooth kinetic profile
Localize Drug Action
- Place drug delivery system in or next to diseased tissue or organ
- Ex: chemotherapeutic wafer (kill anything left behind)
Target Drug Action to Specific Cell
- Carriers or chemical derivatization to target specific cells
- Only specific cells uptake drug and have action on it
Factors that Influence Drug Delivery Rate: Drug
- Solubility (in polymer)
- Partition coefficient (how segregated within polymer)
- MW
- Chemical/physical stability
- Protein binding (probability/propensity)
Factors that Influence Drug Delivery Rate: System
- Material solubility
- Swelling
- MW
- Crystallinity
- Physical stability (degradation)
- Protein binding
Polymeric Drug Delivery Systems
- Matrix —> matrix of polymer with drug inside (more uniform distribution of drug within polymer)
- Reservoir
How are drugs eluted?
- Diffusion
- Erosion
Degradable
- Diffusion and erosion
- Aqueous solutions of body start to interact with polymer, polymer starts to swell
Non-degradable
Diffusion
Swollen Matrix
- More diffusion leads to swollen matrix
- Smaller density of polymer chains
Non-swollen Matrix
Greater density of polymer chains
Factors Influencing Drug Release
- MW
- Crystallinity
- Swelling ratio
- Glass transition temperature
- Crosslink density
Factors Influencing Drug Release: Molecular Weight
- Amorphous polymer —> decrease in MW, increase drug release
- Give chains motion, ends have more motion and more space in between
- More ends, greater diffusivity of drug through polymer chains
- More ends, greater release of drug into system
Factors Influencing Drug Release: Crystallinity
- Increase crystallinity, decrease release rate
- Crystallinity decreases ability to diffuse (greatest diffusivity, fastest release rate)
Swelling Ratio
- How easily water is absorbed into polymer, affinity of polymer for water
- If polymer likes water (extremely hydrophilic) and structure flexible to accommodate water molecules, high swelling ratio
- If swelling, less dense (more free space), greater diffusivity of drug
- Increased swelling ratio, increased release rate
Glass Transition Temperature
- If T_g farther below body T, increased release rate
- Change in density at T_g (above T_g chains moving, below T_g very little motion)
- Decrease T_g, increased release rate
Crosslink Density
- Increase crosslinking, slow down degradation (if erosion slower release rate, if diffusion reduce chain motion/free space)
- Increase crosslink, decrease release rate
