routes of administration (parentals) Flashcards
what is parental administration
administration in ways other than via the GI tract
so e.g
intravenous
intrathecal, epidural and intraspinal
intradermal
subcutaneous
intramuscular
intra-articular
intraocular
what is the intravenous route 1
- Typically via a surface vein.
- From 1ml ‘injection’ up to several liters 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.
intravenous 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.
– Plasma osmolality measures
the body’s electrolyte–water
balance.
– Blood has an osmolality of
275-295 mmmol/kg.
5
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
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.
intradermal injections
inject into the skin between the epidermis and dermis
limited to volumes of 0.2ml
absorption is low
used for immunological diagnostic tests and vaccinations e.g BCG
intramuscular injections
*inject into the tissue of a relaxed muscle in buttock, thigh and shoulder
*aq or oily solutions or suspensions can be administered
*volume up to 4ml
intraspinal injection
-intrathecal injection
-given into cerebrospinal fluid (CSF) in the subarachnoid space or spinal canal
-allow drugs to bypass the blood-brain barrier
-100% drug absorption into the CSF
- volume up to 10ml
-e.g anticancer drugs, antibiotics for meningitis, analgesic
intrapsinal injections
-epidural injection
-given into the epidural space between the dura mater and the vertebrae
e.g spinal anesthetics, long-acting steroid
All intraspinal injections must be isotonic aqueous solutions and cannot include preservatives
intraarticular injections q
-given into the synovial fluid of joints cavities
-suitable for aq solutions and suspensions
for anti-inflammatory drugs to treat arthritic conditions or sports injuries
-100% drug absorption at this site of action
intraocular injections
-intracameral injections
-intravitreal injections
administration of drug into the eyes
*intracameral injections
-into the anterior chamber (in front of lens)
-from 0.1ml to 1ml volume
for antibiotics, local anesthetics during eye surgery
*intraviteral injections
-into vitreous chamber
- to treat various oscular disease
-maximum volume 0.1ml, to minimize risk of rising intraocular pressure and damaged retina
advantages of parental administration routes
-most routes allow rapid onset action
-avoids first pass hepatic metabolism improving bioavailability
-allows a higher concentration of drug in systematic circulation or local site
- suitable for unconscious patients, or unable to administer orally
-delayed onset action is possible through intramuscular injection
-infusion of drugs for prolonged period is possible to maintain steady-state plasma levels
disadvantages of parental routes of administration
-usually requires healthcare professionals to administer
-needle stick injuries
-needle phobia and poor patient acceptability
- formulation and manufacturing costs are higher requiring a sterile and highly controlled pyrogen-free environment
-shelf life is usually shorter than oral forms
-often requires refrigerated storage at extra costs
reasons for addition of excipients
-adjust isotonicity to match human blood
-adjust pH
-increase drug solubility
-increase drug stability
-increase shelf life
*they shouldnt affect drug actions or cause side effects
injection vehicles
- “Water for injections” is the most common vehicle.
– Highly purified grade of water. - “Saline for injections”
– is available in a variety of strength up to 0.9%w/v (isotonic).
– Commonly used as infusion vehicle. - Solubilising agents may be added to aid drug dissolution.
– Surfactants e.g. polyoxyethylene castor oil derivatives can solubilise hydrophobic drugs like diazepam.
– Oil-in-water emulsions using emulsifying agent like lecithin.
– α- and γ- cyclodextrins. - Co-solvent system may be used.
– E.g. ethanol, glycerol, propylene glycol.
preservatives used in parental routes
antimicrobial agents in multi-use products
benzalkonium (0.01% w/v)
benzoic acid (0.17% w/v)
benzyl alcohol (1-2% w/v)
some co-solvents can aid drug solubility and have antimicrobal effect
-ethanol
-glycerol
-propyl glycerol
antioxidants
-reduce drug degradation by oxidation increasing product shelf life
-nitrogen gas is bubbled through the drug solution to displace oxygen in the formulation (sparging)
-filled the container headspace with nitrogen
pH and buffers
physiological pH is 7.4 but optimum pH for injections is 3-9
-pH can be adjusted using:
-acidifying agents (sulfuric acid)
-alkalizing agents (bicarbonate, NaOH)
buffers are used to maintain the optimum pH
works with weak acids
suspending agents
used in suspensions to ensure drug can be readily re-suspended (by shaking) prior to use
-methylcellulose and polysorbates are commonly used
serility
all parentals must be steralised
drug formulations are directly injected into the blood or body tissue bypassing the body’s natural defense mechanism
what are endotoxins and pyrogens
-endotoxins are lipopolysaccharides found in the outer membrane of gram-negative bacteria
-pyrogens are substances that cause fever, typically produced by bacteria or virus
-all parental preparations must be free from endotoxins and pyrogens
-all products must comply with all the tests for bacterial endotoxins and pyrogens
what are the requirements of the following in injections
solutions
suspensions
emulsions
*solutions
-must be clear
-free from visible particles
*suspensions
-readily re-suspended on shaking
-ensure uniform dose to allow withdrawal
*emulsions
-must not show signs of creaming and cracking
what are the category specific requiremnets for infusions
sterile aq solutions or emulsions
water as the continuous phase
isotonic ‘typical volume 100-1000ml
does not contain preservatives
category-specific requirements- concentrates for injections or infusions
diluted with saline for injection or water for injection
often administered through bags
category-specific requirements- powders for injections of infusions
-dry sterile solid in final container for reconstitution
- they require volume of diluent is added prior to administration
-typically used for drugs with short shelf-life after dissolved in solution
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.
– Benzylpenicillin benzathine IM suspension releases drug over 2-4 weeks.
– Hydrocortisone acetate IM suspension releases over 2-7 days
requirements for containers in parentals
-should be transparent to allow particle inspections
-made from glass or plastic
-must be effectively sealed to prevent contamination before use
-be airtight
-container must be compatible with formulation
containers- glass ampoules
- Typically 1-10ml volume.
- For single-use unpreserved products.
- Traditionally use Type 1 glass:
– Little interaction with formulations.
– But fragile and carry safety risk on opening.
– Deposition of glass particles can occur during opening
containers- plastic ampoules
- Now more commonly use blow-fill seal plastic:
– More robust and safer to use.
– Fewer particles generated on opening.
– But more costly and more prone to drug adsorption/absorption than glass.
container- vials
- Made of Type 1 glass with re-usable synthetic rubber closure.
- Range of sizes 5-100ml.
- Rubber closure is held in place by an aluminum cover seal with a flip-off cap
containers- infusion bags and bottles
for larger volumes 100-1000ml, or even 3000ml
- Packaged in:
– 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.
