Pharm Tech Flashcards
What is an ideal drug candidate for CNS delivery (non-Intrathecal)?
MW < 450 Da
H-bond donor < 3
H-bond acceptor < 7
LogP 1-3
Unionised
What are Advantages of Parenteral delivery? (5)
1) Bypasses hepatic first pass metabolism
2) Can control dosage
Relatively low drug concentration (and low toxicity)
3) Direct access to brain (intrathecal)
4) Sustained release (intramuscular depots, intrathecal reservoirs)
5) Ideal for non-compliant, unconscious or dysphagic (difficulty swallowing) patients
What are common types excipients found in solutions for injection? (5)
1) Diluent
2) Buffer salts
3) Tonicity adjusters
4) Preservatives (minimal for intrathecal) -> avoid causing inflammation to the brain
5) Stabilisers/co-solvents
What are considerations for parenteral delivery wrt pH, tonicity and particle size?
1) pH
Ideally 7.4 but a wide range is tolerated
3-11 (intramuscular), or 3-6 (subcutaneous)
Formulation stability is prioritised -> might momentarily feel discomfort when parenteral is first admnistered
2) Tonicity
280-290 mOsm/L for large volume parenterals
* Small volume one doesn’t matter as much
Hypertonic solutions are preferred over hypotonic (but preferably isotonic) -> for hypertonic solutions, water is drawn out from cell, so can flow to other part of body and draw back the water, for hypotonic solution, water flow into blood cells and cause it to burst
* Tonicity can be increased with tonicity adjusters
3) Particle size
No visible particles (more for IV than SC or IM) -> visible particles may block needle or block blood vessel
Intrathecal Administration has what advantage over other parenteral deliveries?
BBB is not a barrier to CNS delivery for IT
What is an ideal drug candidate for transdermal delivery?
Modified Lipinski’s rule of 5
- <500 Da
- 5 or less H-bond donors
- 10 or less H-bond acceptors
- LogP 1-3
- Unionised at physiological pH
What are the advantages of transdermal delivery? (5)
1) Controlled release (through use of reservoirs, duration of contact and/or size of patch). Allows for decreased dosing frequency.
2) No GI degradation/irritation
3) Bypass HFP metabolism
4) Easy termination of input (through removal of patch)
5) Non-invasive; painless
What are the disadvantages/barriers to transdermal delivery? (7)
1) Variability between people and location of administration on body
2) Stratum corneum - barrier leading to slow absorption
3) Skin irritation (interactions and removal)
4) Could be removed by the patient
5) Metabolic enzymes
6) Need to cross BBB (via systemic delivery)
7) Systemic side effects
What are common excipients found in formulations for transdermal delivery? (6)
- Preservatives
- Solvents/co-solvents
- Viscosity modifiers
- Permeation enhancers
- Adhesives
- Matrix polymers
What are the 3 broad types of transdermal patches?
1) Reservoir-type patch (membrane)
- Drug dispersed in a separate depot
- Rate-controlling membrane limits the amt of drug release over time
2) Matrix-type patch
- Drug incorporated in a polymer matrix, separate from the adhesive layer
3) Drug-in-adhesive patch
- Drug combined with adhesive and released from this matrix
What are some factors affecting transdermal delivery? (8)
1) Skin condition (age, disease, injury, site)
2) Skin thickness (of diffusion layer)
3) Hydration of skin (stratum corneum)
4) Stimulation of the skin (phonophoresis/ultrasound, iontophoresis, heat)
5) Physicochemical properties of drug (lipophilicity, diffusion coefficient)
6) Permeation enhancers (reduce barrier resistance of SC without damaging viable cells)
7) Concentration gradient
8) Area of contact between formulation and skin
Describe the structure of the stratum corneum.
- Brick-and-mortar structure
- Ordered, rigid bilayer structure, where access is primarily via intercellular lipidic domains
- Some access via appendages (sweat ducts, hair follicles)
