IC13 Pharm Tech (Parenteral, Intrathecal) Flashcards
What are the different types of parenteral ROA?
Explain intrathecal.
Types of injections:
- Intramuscular, Subcutaneous, Intradermal, Intravenous, Intrathecal (delivered to CSF, flows directly to the brain; administered into reservoir [ommaya] / via lower back)
What are the CSF characteristics?
CSF characteristics:
- pH ~7.3
- 150mL volume
- Ebb and flow circulation –> direction promoted by 1) source & 2) cilia
- Large molecules are cleared more slowly, while small molecules are cleared more quickly within this space
What are the barriers and disadvantages of using non-intrathecal parenteral ROA?
- BBB
- Distribution/dilution (major, since travel everywhere, cause unwanted SE)
- Reticuloendothelial system (phagocytic cells)
- Metabolic enzymes
- Invasive
- Medical professional
- Sterility (strict)
Look at pg 25 of the notes
What is one barrier of non-intrathecal parenteral that intrathecal does not face?
BBB
What are the advantages of parenteral delivery?
Advantage of parenteral delivery
- Bypasses hepatic first pass metabolism (for all parenteral)
- Can control dosage (customizable)
a. Relatively low drug conc. (and low toxicity) - Direct access to brain (intrathecal)
- Sustained release (IM depot, intrathecal reservoirs)
- Ideal for non-compliant, unconscious, dysphagic patients
What are the pathways drugs can use to pass through the BBB?
What are the transporters present on the BBB?
Blood Brain barrier:
- Block 98% of small molecule drugs
- Pathways
o Paracellular (tight junctions)
o Transcellular - Transporters (can be drug targets)
o Active efflux transporter e.g. Pgp, BCRP, MRP –> remove drugs from brain into lumen
o Carrier mediated transporter –> drugs binds and shuttles across the carriers
o Receptor mediated transporter –> drugs binds, transcytosis and exocytosis
What are the characteristics of ideal drug for CNS drug delivery? Including pH, tonicity, particle size.
Modified for CNS
- MW <450 Da
- H bond donors <3
- H bond acceptors <7
- LogP 1-3
- Unionizable
- pH
- Ideally 7.4, 3-11 (IM), 3-6 (SubQ)
- Ensure formulation stability / components do not degrade - Tonicity
- 280-290mOsm/L for large volume
- Hypertonic preferred –> since crenated cells are reversible vs burst cells which are irreversible)
- Tonicity can be increased with tonicity adjusters - Particle size
- No visible particles (esp. for IV)
What are the possible formulations for CNS delivery? Like the type of drug form.
Formulations:
-
Solutions
o Drug molecules
o proteins/peptides -
Suspensions
o Nano/microemulsions
o Liposomes and other lipid-based self-assembled structures
o Nanoparticles
What are the excipients usually found in parenteral formulations?
Excipients:
- Diluent
- Buffer salts
- Tonicity adjusters
- Preservatives (minimal for intrathecal –> since can cause issues with brain)
- Stabilisers / co-solvents –> improve solubility
What are some examples of buffer?
Sodium acetate, citrate, phosphates, lactate
What are some examples of preservatives?
Benzyl alcohol, chlorbutanol, methylparaben, propylparaben, phenol, thiomersal
What are some examples of tonicity adjuster?
Mannitol, NaCL, glycerin/glycerol, glycine
What example is a Cryoprotectant (prevent freezing damage to components in lyophilized formulations)?
Mannitol
What are some examples of a solvent?
Ethanol, glycerin/glycerol, glycine, PEG (mixed), propylene glycol
What are some examples of a surfactant?
Polysorbate 20 & 80
