IC10 Pharm Tech II (Parenteral)

Question 1

Types of injections (5)

Answer 1

• IM: into muscles (90 degree)
• SC: into subcutaneous layer (45 degree), hydrophobic
• IV: into vein (25 degree)
• Intradermal: into skin (epidermis)
• Intrathecal: into spinal fluid

Question 2

Where are drugs delivered to for intrathecal injection?

Answer 2

drugs delivered to CSF → flows directly to brain

Question 3

How can drugs for intrathecal injection be administered?

Answer 3

drugs can be administered into reservoir (Ommaya) or via lower back

Question 4

Difference between intrathecal and epidural

Answer 4

• Intrathecal: drugs enter CSF → to brain (need lower concentration of drug for therapeutic effect); high potential for complications than epidural
• Epidural: effect is slower (drug slowly diffuse to CSF); less SE than intrathecal

Question 5

CSF (pH, volume, viscosity, flow rate and pressure)

Answer 5

• pH ~7.3
• 150mL volume (fast turnover of CSF)
• Variable viscosity, flow rate and pressure at different sites → may affect how the drug works

Question 6

What affects the flow of CSF

Answer 6

Ebb and flow ‘circulation’ - direction promoted by source and cilia

Question 7

Barriers/ disadvantages of parenteral delivery (7)

Answer 7

• Non-intrathecal (IV, SC, IM) need to cross BBB (only intrathecal bypass BBB)
• Drug is diluted/distributed to other parts of the body (more for non-intrathecal than intrathecal)
• Reticuloendothelial system (phagocytosis of foreign substances eg drugs)
• Metabolic enzymes
• Invasive
• Need trained medical professional to administer
• Strict sterility (intrathecal need stricter sterility)

Question 8

What can be done to overcome dilution/distribution (more for other parenteral, less for intrathecal)

Answer 8

active targeting molecule added to drug -> less off target SE

Question 9

Advantages of parenteral delivery (5)

Answer 9

• Bypass hepatic first pass metabolism
• Can control dosage → know how much of drug administered entered the blood (no need account for absorption/ bioavailability)
• Direct access to brain (intrathecal)
• Sustained release of drug (IM depots and intrathecal reservoirs)
• Ideal for non-compliant, unconscious, dysphagic (unable to swallow) patients

Question 10

Why does BBB prevent entry of most drugs?

Answer 10

Epithelial cells in BBB have tighter connective tissues btw cells → harder for drugs to pass through

Question 11

How does drug enter the brain?

Answer 11

1. Paracellular transport (btw cells)
2. Transcellular transport (across cells)

Question 12

2 modes of transcellular transport

Answer 12

1. Carrier mediated transport (CMT)
2. Receptor mediated transport (RMT)

Question 13

How does drug exit the brain?

Answer 13

ACTIVE efflux pump transporters (eg P-gp, BCRP, MRP)

Question 14

Ideal drug candidate (Lipinski’s rule of 5)

Answer 14

MW: <500 Da
H bond donor: ≤5
H bond acceptor: ≤10
LogP: <5
Ionisation state: Unionised

Question 15

Ideal drug candidate for CNS delivery (stricter criteria)

Answer 15

MW: <450 Da
H bond donor: <3
H bond acceptor: <7
LogP: 1-3 (not too hydrophobic)
Ionisation state: Unionised

Question 16

Considerations for parenteral delivery (pH, tonicity, particle size)

Answer 16

• pH: ideally 7.4 but wide range tolerated (IM: 3-11, SC: 3-6)
• Tonicity (very important): 280-290 mOsm/L for large volume parenteral. preference: isotonic > hypertonic > hypotonic
• Particle size: no visible particles (more for IV than SC or IM)

Question 17

Why is hypertonic preferred over hypotonic?

Answer 17

• Hypertonic formulation: water exit RBC, but RBC can get back shape in areas of the body with high water volume
• Hypotonic formulation: water enter RBC, RBC burst (irreversible)

Question 18

What is the concern with large particle size for parenteral administration?

Answer 18

Large visible particles can cause embolism during administration

Question 19

Diluent/solvent eg

Answer 19

water, ethanol, glycerin, glycerol, PEG, propylene glycol

Question 20

Buffer eg

Answer 20

(weak acid/salt) acetate, citrate, phosphate, lactate

Question 21

pH adjusters eg

Answer 21

(strong acid/base) HCl, NaOH

Question 22

Preservatives eg

Answer 22

benzyl alcohol, chlorobutanol, parabens, phenol, thiomersal

Question 23

Cryoprotectant eg

Answer 23

mannitol

Question 24

Tonicity adjusting agents

Answer 24

mannitol, sorbitol, NaCl, glycerin, glycerol, glycine

Question 25

Surfactant eg

Answer 25

polysorbate 20 & 80

Question 26

How are parenteral drugs stored?

Answer 26

• Glass ampules — scored for breakage
• Glass vials with rubber stoppers — for powders that require constitution, sterile water can be included with product
• Pre-filled syringes — graduated

Question 27

Consideration for formulation and material of container

Answer 27

must be able to withstand sterilisation processes (eg heat, UV, gamma radiation sterilisation)

Question 28

Parts of a syringe, which parts requires lubrication?

Answer 28

• needle, barrel, plunger
• barrel and plunger may be lubricated with silicon
• Single-use and sterile
• Intrathecal spinal needle are more flexible than normal syringes

Question 29

Concerns with use of silicon with formulation/drug

Answer 29

lubricants may interact with formulation/ drugs → need to do testing for regulatory approval

Question 30

Function of catheters and reservoirs for sustained released infusion of drugs

Answer 30

• Reservoir for refilling of drug
• Catheter to deliver drug
• Pump to automat dosing → must be reliable for duration of use

Question 31

What must the equipments be made of?

Answer 31

Biocompatible material (eg titanium) of the equipments due to extended duration that implants have to exist in the body

Question 32

Zwitterion

Answer 32

zwitterion (+ & -) if both COOH and NH2 are charged — overall 0 net charge

Question 33

Intrathecal vs IV (CL and half life)

Answer 33

• Intrathecal: lower CL, longer half life than IV
• IV need to give higher dose and increase frequency — may decrease patient compliance