Lecture 14 - Drug Delivery Flashcards
1
Q
Classic Drug Delivery
A
Oral or injection delivery
Problems:
- Reduced potencies because of partial degradation
- Toxic levels of administration
- Increase costs associated with excess dosing
- Compliance issue due to administration pain
2
Q
Controlled Drug Delivery
A
- Maintain therapeutic drug level for prolonged periods of time
- Predictable controllable release rates
- Reduce dosing frequent and increase patient compliance
3
Q
Encapsulation
A
Involves surrounding drug molecules with a solid polymer shell (reservoir system)
4
Q
Entrapment
A
Involves the suspension of drug molecules within a polymer matrix (matrix system)
5
Q
Fabrication of Drug Release System by Entrapment or Encapsulation
A
- Wurster
- Coacervation
- Spray drying (or precipitation)
- Coextrusion
- Self-assembly methods
6
Q
Wurster
A
- Coating applied after a drug core is formed
- Polymer shell applied via spraying while the drug cores (liquid or solid) are suspended and recirculated in a gas stream
7
Q
Coacervation
A
- Polymer dissolved in solvent (water-insoluble)
- Drug dissolved in water
- 2 liquids rapidly mixed
- Water droplets form within the solvent to form emulsion
- Emulsion mixed rapidly with fresh water
- Oil droplets within fresh water phase
- Oil droplets contain original dispersed water/drug phase
- Oil diffuses into fresh water phase precipitating the polymer and entrapping the drug
8
Q
Coextrusion
A
- Polymer shell is flowed concentrically around a pipe containing the drug formulation
- These concentric cylinders then breakup into individual packets either driven by air flow, electrostatic or mechanical vibration
9
Q
Self-Assembling
A
- Polymers self assemble with drugs to create drug delivery vehicles
Two approaches: - Using a molecule that has a hydrophilic head and hydrophobic tail to form a shell
- Electrostatic interaction to entrap drug molecules
10
Q
Self-Assembling: Approach #1
A
- Using surfactants or block copolymers and drug to form liposome
- Typically formed by homogenization or extrusion through polycarbonate membranes
- Small liposomes (10-50nm) prepared by taking suspensions and passing them through fine matrix polycarbonate membrane
- Medium liposomes (50nm-1um) prepared by hydration of a dry surfactant or block copolymer film by an aqueous solution
- Large liposomes (100nm-20mm) prepared by vigorous agitation (homogenization) during the hydration process
11
Q
Self-Assembling: Approach #2
A
- Ionic attraction between dissimilar charged molecules can be used to attach a molecule to the drug
- The resulting complex may provide protection by containing the drug molecule on the interior
- Complexes are prepared by vigorously mixing aqueous solutions of the surfactant and drug
- The complex either precipitates as a solid or can be separated by partitioning to an organic solvent
12
Q
Targeting Drug Delivery
A
- Controlled drug delivery in a target site (cells or tissue)
- The coating or matrix surrounding the drug molecule can be used to direct the particle to a targeted site
- Such systems include: liposomes, microparticles, antibodies, enzymes and other proteins
13
Q
Microparticles Enhanced Targeting
A
- Particle sizes ranging from 10nm to 1mm and effect biodistribution
- Particles less than 10nm are 400 times more likely to cross intestinal wall than 1um particles
- Particles between 1 and 10um deposit in the deep lung via impaction while other escape during breath or deposit in the mouth
- Particles below 500nm can escape filtering effects of the liver and kidney for several cycles
- Nanoparticles with high surface to volume ratio - effects cellular interaction
14
Q
Antibody Enhanced Delivery
A
- The attachment of antibodies to delivery vehicles can be used to increase tissue specificity and sensitivity
- Attachment occurs by physical adsorption or covalent bonding
- Monoclonal antibodies can be directed against a single determinant - similar to a lock and key
15
Q
Drug Release by Diffusion
A
- When polymer absorbs water it swells in size
- Swelling creates voids throughout the interior polymer
- Smaller molecule drugs can escape via the voids at a known rate controlled by molecular diffusion (function of temperature and drug size)
