Drug Delivery Systems Flashcards
What factors should be considered for drug delivery?
- Drug physico-chemical properties
- Body effects and interactions
- Improvement of drug effect
- Patient comfort and well being
Depends upon concentration achieved at the site
of action which depends on:
- Dosage
- Extent of absorption
- Distribution to the site
- Rate/extent of elimination
List conventional drug delivery systems
enteral
parenteral
other
List controlled drug delivery systems
sustained
extended
site-specific
pulsatile
List some barriers to protein drug delivery
enzymatic
intestinal epithelial
capillary endothelial
blood brain
Explain enzymatic barriers
limits absorption of protein drugs from GI tract
Explain intestinal epithelium barrier
involved in the transport of protein drugs across the intestinal epithelium
Explain blood brain barrier
involved in transport of protein drugs to brain compartment
List some approaches to enhance bioavailability of proteins
increase the permeabiliyt of absorption barrier
decrease pepitdase activity at the site of absorption and along the absorption route
Explain how to increase the permeability of absorption barrier
addition of fatty acids/phospholipids, bile salts and others
through iontophoresis
by using liposomes
Explain how to decrease peptidase activity at the site of absorption
protease inhibitors
enhance resistance against degradation by modification of the molecular structure
prolongation of exposure time
Explain iontophoresis
a transdermal electrical current is induced by positioning two electrodes on different places on the skin
Reasons why drugs fail
active compound never reaches the target
molecules do not enter cells
small fraction of drug reaches the site
What should be balanced when determining targeted drug therapy?
should maximize the therapeutic effect and avoid toxic effects elsewhere (few s/e)
Drug targeting is the concept where attempts are made to increase the therapeutic efficacy of drugs by…
specific delivery of the active compound at its site of action
to keep it there until it has been inactivated and detoxified
Recent progress can be ascribed to the understanding
of :
nature of anatomical and physio barriers
new insights of pathophysiology of diseases
rapidly growing number of technological options for drug delivery
What is the difference between active and passive targeting?
drug goes to target b/c attached to homing device
natural system
When to target drugs?
drugs with high total clearance
increase in the rate of elimination of free drugs
response sites with a relatively small blood flow require carrier-mediated transport
What are factors of particulate carriers dependent on?
size
charge
surface hydrophobicity
presence of homing devices on their surface
Advantages of liposomes over other particulate systems are…
low toxicity, safety record
large aqueous core (more space for the drug)
changing characteristics to control disposition
PEGylation
What is PEGylation?
the process of covalently attching PEG to another molecule
it can prevent an immune response
increase the ability of a drug to be soluble in water
add targeting molecules
What are the limitations of liposomes?
poor access to target sites outside the blood circulation
high resistance to penetrate the endothelial linging
target sites should be sought in the blood circulation
What is the aim for rate controlled delivery?
to optimize the therapeutic benefit of the drug
What are the two types of controlled release systems?
rate control through open loop type approach
rate control though closed loop approach (feedback)
What is pulsatile delivery?
desired mode of input for a number of protein drugs and for these drugs, pumps should provide flexible input rate characteristics
What are mechanical pumps?
are common tools to administer drugs intravenously in hospitals
How does osmotically driven systems work?
- the incoming water empties the drug containing reservoir surrounded by a flexible impermeable membrane
- the release rate depends on the characteristics of this semi-permeable membrane and on osmotic pressure differences over this membrane
- the protein solution must be physically and chemically stable at body temperature over the full term of the experiment
- moreover, the protein solution must be compatible with the pump parts to which it is exposed
What is the limiting of osmotically driven system?
the fixed release rate, which is not always desired
What is an open loop insulin pump- type 2?
combines insulin administration by continuous subcutaneous infusion and monitoring of glucose levels
What is the disadvantages of open insulin pump?
The patient still has to collect data to adjust the pump rate. This implies invasive sampling from body fluids on a regular basis followed by calculation of the required input rate.
2. Pump may fail?
3. Drug stability
What is the goal of closed loop insulin pumps?
to have a system where regulation of insulin injections are directly based on current blood reading
do not require pt to be involved
readings must be in real-time
How does protein delivery by microencapsulated secretory cells work?
prevent cell migration
stops rejection by immune cells
takes the drugs as far as it can before releasing
