ic10 parenteral delivery Flashcards
types of injections, target, and angle of injection
1) intramuscular (90º) (muscle)
2) subQ (45º) (SC)
3) intravenous (25º) (dermis)
4) intradermal (10-15º) (epidermis)
5) intrathecal (into the spinal fluid)
intrathecal vs epidural delivery?
epidural space is not direct to the brain, it slowly diffuses from the epidural space to the CSF;
only the intrathecal has direct access to the brain because it is delivered directly to the cerebrospinal fluid
another method of intrathecal delivery
DELIVERY into the ommaya reservoir, which is a plate (placed at the cranium) where the drug can be loaded into and released overtime.
INVASIVE
properties of the CSF?
vol, properties, composition
1) VOL: 150ml
- high turnover
- 430-530mL produced per day
2) PROPERTIES
- variable viscosity, flow rate, pressure
- pH ~7.3
- fluctuation in flow: direction promoted by source and cilia. ebb & flow
3) COMPOSITION
- clear solution: 99% water, 1% protein, ions, neurotransmitters and glucose
barriers to intrathecal delivery (and potential advantages compared to other parenteral?)
- do need to bypass BBB and less dilution/distribution with peripheral space (ONLY CSF)
- LOSS from: metabolic enzymes, reticuloendothelial system
- invasive
- requires medical professional
- needs to be (strictly) sterile
reduce Vd
can increase half-life and reduce clearance
advantages of parenteral
1) bypass hepatic 1st pass metabolism
2) can control dosage = only require a low drug conc = less toxicity/more predictable side effect profile
3) direct access to brain
4) ideal for non-compliant/ unconscious/ dysphagic patients.
5) sustained release via intramuscular depots/intrathecal reservoirs
movement of transport across BBB?
PARACELLULAR
TRANSCELLULAR
- carrier mediated transporters (CMT) = complementary on both sides, shuttering drug across epithelial cells via endocytosis –> exocytosis
- receptor mediated transporters (RMT)
problems affecting transport across BBB?
presence of active efflux transporters eg P-gp, BCRP (breast cancer resistance protein), MRP (multi-drug resistance proteins) removing drug from brain to lumen (blood)
If paracellular,
- tight junctions = presence of occludin and JAM inhibiting transport
ideal drug property for parenteral non intrathecal?
should follow the lipinski, with some modifications
<450Da
<3 HBA
<7 HBD
logP 1-3
unionised
common excipients for injection
diluent
buffer salts
tonicity adjusters
preservatives (minimal for intrathecal)
- ensure sterility to avoid sepsis
stabiliser/co-solvent
considerations for physiochemical properties of parenteral drugs
ideally 7.4, prioritise stability
- 3-11 for IM
- 3-6 for SC
tonicity
- 280-290mOsm/L for large vol parenteral
- hypertonic > hypotonic preferred
particle size
- no visible particles = could result in embolism?
what are the buffers used
sodium citrate/acetate/phosphate(mixed)/ lactate
what are the preservatives used
alcohol types:
- benzylalcohol, chlorbutanol, phenol
paraben types:
- methylparaben, propylparaben
and
- thiomersal
what are the tonicity agents
mannitol
sodium chloride
glycerin/glycerol/glycine
what are the solvents
ethanol
PEG
propylene glycol
glycin/glycerol/glycerine
