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
what are the surfactants
polysorbate 20 and 80
packaging and storage of parenteral drugs
glass ampoules should be scored for breakage
glass vials with rubber stoppers for powders that require reconstitution
properties of syringes
1) needle
- different sized gauges
- can break skin
2) barrel
- should be graduated
- can be lubricated
3) plunger
- lubricated with silicone
IDEALLY: single use and sterile
biocompatible materials for catheters and reservoirs?
titanium
zwitterions
charges get cancelled out at pH7
problem with silicone lubricant
may have physical or chemical interactions with the drug or solution
