Routes of Administration - parenterals Flashcards
Describe intravenous (IV) route (1)
- Typically via a surface vein.
- From 1ml ‘injection’ up to several litres for ‘infusion’.
- IV injection rapidly increases plasma drug concentration.
- Provide 100% drug absorption.
- Infusion (drug is diluted in an infusion bag) provides a slow and controlled drug release.
What does parenteral administration mean?
- Drug administration other than via the GI tract e.g. skin
Describe intravenous (IV) route (2)
- Water-in-oil emulsions or suspensions cannot be
administered via IV as oil phrase or suspended drugs
can block blood vessels. - Hypertonic or extreme pH drug solutions can cause
inflammation and pain at injection site.
Describe subcutaneous injections.
- Also called hypodermic injections.
- Inject into the loose connective and adipose
tissues immediately below the dermal skin layer. - Typically in the abdomen, upper arms/legs.
- Highly vascular site, so absorption is rapid and
predictable. - Aqueous solutions or suspensions can be administered.
- Volumes up to 1 ml.
- E.g. insulin.
Describe intra-arterial and intracardiac injections.
- Intra-arterial is like IV administration except it is via
artery.
– More invasive and less accessible than via the veins.
– Only used when IV access cannot be established e.g.
pre-mature babies. - Intracardiac route is used only in life-threatening
emergencies to produce a rapid, local effect in the
heart.
Describe intradermal injections
- Inject into the skin between the epidermis and dermis.
- Limited to volumes of up to 0.2ml.
- Absorption is slow.
– Little interstitial fluid to facilitate drug diffusion at injection
site.
– Not well-perfused by blood. - Used for immunological diagnostic
tests and vaccinations. E.g. BCG.
Describe intramuscular injections.
- Inject into the tissue of a relaxed muscle in buttock,
thigh and shoulder. - Aqueous or oily solutions or suspensions can be
administered. - Absorption is slower than SC.
- Volume up to 4 ml.
Describe intraspinal injections - intrathecal
– This is given directly into the cerebrospinal fluid (CSF) in
the subarachnoid space or spinal canal.
– Allow drugs to bypass the blood brain barrier.
– 100% drug absorption into the CSF.
– E.g. anticancer drugs (methotrexate), antibiotics for
meningitis, analgesic.
– Volumes up to 10ml
Describe intraspinal injections - epidural
This is giiven into the epidural space between the dura mater and the vertebrae.
– E.g. spinal anaesthesia, long acting steroid.
* All intraspinal injections must be isotonic aqueous solutions
and cannot include preservatives
Describe intra-articular injections.
- Given into the synovial fluid of joints cavities.
- Suitable for aqueous solutions and suspensions.
- For anti-inflammatory drugs to treat arthritic conditions
or sports injuries. - 100% drug absorption at site of action.
Describe intraocular injections.
- Administration of drug into the eyes and sub-classified
into:
– Intracameral injections - Into the anterior chamber (in front of the lens).
- From 0.1ml to 1ml volumes.
- For antibiotics, local anaesthetics during eye surgery.
– Intravitreal - Into the vitreous chamber.
- To treat various ocular diseases (e.g. endophthalmitis).
- Max. vol. 0.1ml – minimise risk of rising intraocular
pressure and damage retina.
What are the advantages of parental routes?
- Most routes allow rapid onset of action.
- Avoids first pass hepatic metabolism thus improves
bioavailability. - Allows higher concentration of drug in the systemic
circulations or local site. - Suitable for unconscious patients, or unable to administer orally.
- Delayed onset of action is possible through intramuscular injection.
- Infusion of drugs for prolonged period is possible to maintain steady-state plasma level.
What are the disadvantages of parenteral routes?
- Usually requires healthcare professional to administer.
- Potential risks during administration e.g. air embolism, haemolysis.
- Needle-stick injuries.
- Needle phobia and poor patient acceptability.
- Formulation and manufacturing costs are higher requiring sterile and highly controlled pyrogen-free
environment. - Shelf-life is usually shorter than oral forms.
- Often requires refrigerated storage (extra cost).
Why are excipients added?
– Adjust isotonicity to match human blood.
– Adjust the pH.
– Increase drug solubility.
– Increase drug stability.
– Increase shelf life.
What vehicles are used for injections?
- Highly purified grade of water
- Saline - commonly used as an infusion vehicle
- Solubilising agents
- Co-solvent systems e.g. ethanol, glycerol
Why are solubilising agents added?
- To aid drug dissolution
For example: - Surfactants can solubilise hydrophobic drugs like diazepam
- Oil-in-water emulsions
- alpha and gamma cyclodextrins
What are preservatives?
- Antimicrobial agents are added in multi-dose products
(e.g. vials with a rubber septum). - Some co-solvents can aid drug solubility and have
antimicrobial effect:
– Ethanol
– Glycerol
– Propylene glycol
What are the common preservatives used in parenteral products?
– Benzalkonium chloride
– Benzoic acid
– Benzyl alcohol
What are antioxidants?
- Reduce drug degradation by oxidation thus extend
product shelf-life.
Give an example of an antioxidant and how it is used.
- Nitrogen gas is bubbled through the drug solutions to
displace oxygen in the formulation.
– Called ‘sparging’. - Fill the container headspace with nitrogen.
What is the physiological pH?
7.4
What is the acceptable pH for injectable products?
What happens outside this pH range?
- 3-9
- pH outside this range is too corrosive and can cause tissue damage.
How can pH be adjusted?
– Acidifying agents e.g. hydrochloric, citric, sulphuric acids.
– Alkalizing agents e.g. Na bicarbonate, Na citrate, NaOH.
Why are buffers used?
- Buffers are used to maintain the optimal pH:
– Work best when the pH is close to the pKa of the weak
acid/base.
State the osmolality of blood.
275-295 mOsm/kg
What do hypotonic solutions cause?
Cells to swell and burst
What do hypertonic solutions cause?
Cells to lose water and shrink
What should IV infusions be?
isotonic
What can be added to hypotonic solutions?
NaCl, dextrose or mannitol
How can hypertonic solutions be made isotonic?
- Dilution prior to administration.
State the use of suspending agents.
- Used in suspensions to ensure drug can be readily re-suspended (by shaking) prior to use
What are commonly used suspending agents?
- Methylcellulose
- Polysorbates
Why must all parenteral preparations be sterile?
- Drug formulations are directly injected into the blood or body tissue bypassing the body’s natural defence
mechanisms.
What are endotoxins?
- They are lipopolysaccharides found in the outer membrane of gram-negative bacteria
What are pyrogens?
- Substances that cause fever, typically produced by bacteria or viruses
Why must products be free of visible particles and have low numbers of sub - visible particles?
- Any suspended particles will travel through the venous system to the lung, preventing blood flow, and could result in pulmonary embolism
What are the category-specific requirements when injections are solutions?
- Must be clear
- Free from visible particles
What are the category-specific requirements when injections are suspensions?
- Readily re-suspended on shaking
- Ensure uniform dose to allow withdrawal
What are the category-specific requirements for emulsions?
- Must not show signs of creaming or cracking
What are the category-specific requirements for aqueous injections?
- Must contain an antimicrobial preservative
- Preservative cannot be used if dose volume is greater than 15 ml or injecting into the eye or the spin
What are the category-specific requirements for infusions?
- Sterile aqueous solutions or emulsions.
- Water as the continuous phase.
- Isotonic.
- Typical volume 100ml-1000ml.
- Do not contain preservatives.
What are the category-specific requirements for concentrates for injections or infusions?
- For injection or infusion after dilution.
- Typically diluted with saline for injection or water for
injection. - Often administered through infusion bags.
What are the category specific requirements for powders for injections or infusions?
- Dry sterile solid in final container for reconstitution.
- The required volume of diluent is added prior to
administration. - Typically used for drugs with short shelf-life after dissolved in solution.
Describe suspensions for injections.
- For SC, IM and intra-articular administration.
- Suspended drug must first dissolve before absorption
take place. - Allow slow and prolonged release thus can reduce
dosing frequency. - Drugs with low aqueous solubility may use IM route to
provide a prolonged effect.
Why should the material used for containers be transparent?
Allows inspection for particles before use
What must containers be made from?
Glass or plastic
Why must containers be sealed?
- To prevent contamination before use
When are glass ampoules used as containers?
- Typically with 1-10ml volume
- For single-use unpreserved products
Why is Type 1 glass used?
- Little interaction with formulations
- But fragile and carry safety risk on opening
- Disposition of glass particles can occur during opening
Why are plastic ampules more commonly used as containers?
– More robust and safer to use.
– Fewer particles generated on opening.
– But more costly and more prone to drug
adsorption/absorption than glass.
What are vials made of?
Type 1 glass with re-usable synthetic rubber closure
What does the aluminium cover seal with a flip-off cap act as in vials?
- Acts as dust protection and as a security measure
- Often coated in Teflon to minimise interaction with drug
When are infusion bags and bottles used as containers?
- For large volume from 100ml-1000ml or even 3000mL
What are infusion bags and bottles packaged in and describe them.
– Collapsible infusion bags
* Made from PVC or poly-olefin plastic.
* Have an additive port to allow other
injectable drugs to be added.
* Air inlet is not needed.
– Semi-rigid plastic bottles
* Made of polyethylene.
* Air equilibration may be required.
– Glass bottles
* less commonly used now.
