Pharmaceutical Technology 2 Flashcards
Types of injections
- Intramuscular - into muscle
- Subcutaneous - into subcutaneous layer
- Intravenous - into vein
- Intradermal - into epidermis
- Intrathecal - into spinal cord
(Intrathecal injections) Drug delivered into ______ flows directly to the ____.
CSF
Brain
How can drugs be administered for intrathecal injections?
a. Into reservoir (Ommaya)
b. Via lower back
CSF is a clear solution made up of?
99% water
1% protein, ions, neurotransmitters & glucose
pH of CSF
~7.3
Volume of CSF
150mL, 430-530mL produced per day
CSF has variable ____, ____ and ___.
Viscosity
Flow rate
Pressure
Can intrathecal cross the BBB?
Yes
Advantages of parenteral delivery 1
Bypasses hepatic 1st pass metabolism
Advantages of parenteral delivery 2
Can control dosage
- Relatively low drug concentration and low toxicity
Advantages of parenteral delivery 3
Direct access to brain (intrathecal)
Advantages of parenteral delivery 4
Sustained release (intramuscular depot, intrathecal reservoirs)
Advantages of parenteral delivery 5
Ideal for non-compliant, unconscious or dysphagic patients
From blood to brain, drug solution flows through ______.
Circulatory system
- Reticuloendothelial system (RES)
- Unless there is active targeting, drug will distribute everywhere
Drugs must bypass ____ to access the brain.
BBB
The blood brain barrier blocks uptake of __% of small molecular drug candidates.
98%
Types of transportation across BBB
Paracellular (tight junctions)
Transcellular
Examples of active efflux transporters
P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), multi-drug resistance proteins (MRP)
What are active efflux transporters?
Removes drugs from organ (brain) into the lumen (blood)
Types of transporters in BBB
- Active efflux
- Carrier mediated (CMT)
- Receptor-mediated (RMT)
Modified Lipinski’s for CNS - MW
<450 Da
Modified Lipinski’s for CNS - hydrogen bond donors
<3
Modified Lipinski’s for CNS - hydrogen bond acceptors
<7
Modified Lipinski’s for CNS m- LogP
1-3
Modified Lipinski’s for CNS - ionisation state
Unionised
Delivery system - solutions
a. drug molecules
b. proteins/peptides
Delivery system - suspensions
a. Nano/microemulsions
b. Liposomes and other lipid-based self-assembled structures
c. Nanoparticles
Common excipients of solutions for injection
- Diluents
- Buffer salts
- Tonicity adjusters
- Preservatives (minimal for intrathecal)
- Stabilisers/co-solvent
pH consideration for parenteral delivery
Ideally 7.4 but wide range tolerated
Intramuscular: 3-11
Subcutaneous: 3-6
Tonicity consideration for parenteral delivery
280-290 mOsm/L for large volume parenteral
Hypertonic > hypotonic (can increase with tonicity adjuster)
Particle size consideration for parenteral delivery
No visible particles (more for IV than SC/IM)
Benzyl alcohol
Preservative
Ethanol
Solvent
Glycine
Solvent
PEG (mixed)
Solvent
Propylene glycol
Solvent
Glycerin/glycerol
Solvent/tonicity adjustment
Glycine
Solvent/tonicity adjustment
Thiomersal
Preservative
Mannitol
Tonicity adjusting agent / cryoprotectant
Sodium acetate, citrate, and phosphates (mixed), lactate
Buffer
Function of reservoir in infusions
Refilling
Function of catheter in infusions
Delivery
Function of pump in infusions
Automate dosing
Biocompatible material in infusion
Titanium
Haloperidol formulation
50mg/mL or 100mg/Ml injection
Site of administration of Haloperidol
IM into gluteal region
Interval between doses for Haloperidol
4 weeks
Half-life of Haloperidol
3 weeks
Baclofen route od adminitration
Intrathecal injection
Baclofen concentration in ____ is 100x higher than after _________.
CSF
Oral administration