Parenteral Drug Delivery Flashcards
Routes of injection
INTRAVENOUS = drug injected into the vein (>5ml)
INTRAMUSCULAR = drug injected into the muscle mass (2ml)
SUBCUTANEOUS = drug injected into the loose connective tissue (1.3ml)
INTRADERMAL = drug injected into the superficial layer of the skin (0.1ml)
Minor routes = intrathecal, intra-arterial, intra-articular, intra-cardiac, intraosseous
What are the specialised formulation needs of parenterals?
Sterility essential
Isotonic + pH 7
Most routes only allow small volumes
Why use parenterals?
Speed of action
- IV drug enters plasma immediately
- Rapidly disperse to tissues
Local/targeted drug effect
- e.g. local anesthetics, cytotoxics
100% bioavailability
- drug does NOT have to cross absorption barriers in gut
- can administer drugs that are unabsorbed/degraded
kmProblems + precautions of parenterals
TOPICABSF
- Air embolism – injection of air bubbles
- Bleeding (e.g. in haemophilia)
- Cost (training & specialised formulation)
- Fever (from pyrogens)
- Infiltration / extravasation (local tissue damage)
- Overdosage (serious due to rapid onset)
- Particulates (pulmonary embolism)
- Sepsis (sterile practice)
- Thrombosis (blood clot)
IV Advantages + Disadvantages
Rapidity - immediate effect
More predictable response than other routes (no issue on poor/incomplete absorption)
Preferred for orally inactive drug
Suitable for unconscious, uncooperative + nauseous pts
However,
Requires extensive training
Sterility must be maintained
Dosage error can lead to serious injury/death
Complications e.g. extravasation, thrombosis, air embolism, phlebitis, haemolysis etc
Site availability
Biopharmaceutics of IV route
- Drug injected into vein – passed to heart
- Passes through pulmonary circulation
- Heart then pumps it around tissues
- Blood flow in tissues is slow, so absorption is efficient (approx. 1 mm s -1)
- Drug returns to heart through liver – metabolism begins
- Round trip takes 10 – 30 secs
IV Bolus injection
Rapid increase in drug conc in blood plasma
Distribution causes conc to fall
Drug conc remaining in blood plasma affected by dose given + amount of drug transferred into body tissues
Slower decrease in drug conc due to irreversible excretion + metabolism
IV Infusion
Administers large volume of fluid @ slow rate
- ensures drug enters general circulation @ constant rate
Drug conc. in blood plasma rises soon after start of infusion + achieves steady state when rate of drug addition = rate of drug loss
Stopping infusion causes elimination of drug from body by metabolism + excretion follows 1st order kinetics
IV administration
Small volumes can be injected directly
Small volumes often mixed into other LVPs - can cause extensive compatibility problems
Larger volumes via central venous catheter emptying into subclavian vein
Continuous infuson via drip feed or by metering pump
Ambulatory + implantable pumps offer continuous treatment out of hospital environment/patient-controlled analgesia
Formulation requirements of small volume parenterals (<100ml)
Sterile + particle free
pH from 3 to 9 as long as injection is slowly/rapidly diluted
- pH > 9 causes tissue necrosis
- pH < 3 pain + phlebitis in tissue
- Use acetate, citrate + phosphate buffers
Co-solvents + preservatives = allowed
Surfactants can be used to aid solubility
Formulation requirements for large volume parenterals (>100ml)
Used as electrolyte balance, parenteral nutrition, plasma replacement, acid-base balance, contrast agents
pH 6-8
Made isotonic with glucose/NaCl
- hypotonic sol - fluid pass into blood cells by osmosis, blood cells swell + burst
- hypertonic sol - red blood cells lose fluid + shrink
Preservatives NOT permitted
IM delivery
Injection of a dose form into muscle tissue, from where it is absorbed due to perfusion of the muscle by blood
Muscle is well supplied with blood so absorption = rapid
Provides effect slowly but more lasting than IV
Inject solutions, suspensions, depot implants
Don’t need to be water miscible
Small volume route
Pharmacokinetics of IM delivery
IM Delivery involves:
- release of drug from dose form into intracellular fluid
- Absorption from ICF into blood + lymphatics
- Transport from local blood volume to general circulation
- Metabolism
IM Advantages + Disadvantages
Rapid absorption
Formulate sustained depot
Implanted devices removable
However,
Local muscle damage
Can;t use in cardiac failure (no muscle perfusion)
Avoid blood vessels
Common injection sites on adults, young children + infants
Point of injection - AFAP from major nerves or blood vessel, otherwise there is risk of injuries
Adult - upper outer quadrant of gluteus maximus
- deltoid can be used, but more painful
Infants - gluteal area = small** & composed primarily of **fat
- muscle poorly developed
- injection in this area too close to sciatic nerve, esp. child is resisting injection
Infants & young children - deltoid muscles of upper arm or midlateral muscles of thigh
- injection at upper or lower portion of deltoid, well away from radial nerve
Factors affecting IM absorption rate
Hydrophobic drugs do not dissolve in ICF
Ionised + water-soluble drugs will NOT be able to cross capillary membrane
Protein-bound drugs are slowly absorbed since their activity in solution = low
Some drugs in solution is absorbed slowly if composition of formulation changes after injection
Muscle movement + blood flow
Intradermal delivery
Epidermal tissue have little available fluid + poorly perfused by blood
Usual site = anterior forearm
Epidermal injection persists @ site for long periods + available volume for injection = small
e.g. tuberculin + allergy testing
Subcutaneous delivery
Injection into fatty + connective tissue beneath skin
Injection prepared as aq. solution/suspensions
Injected in small volumes of 1.3 to 2 ml
Common injection site = anterior abdomen (belly), upper arm, thigh + bum.
Absorption of insulin in thigh site faster than abdominal
Less well perfused than IM route so slower absorption
Cannot give irritating solutions
How is insulin administered\
How does insulin’s formulation affect its action?
Insulin is given subcutaneously
Inactivated by liver + kidney
10% excreted in the urine
Different formulations vary in timing of peak effect + duration of action:
- Soluble insulin = rapid + short-lived effect
- Longer-acting preps = produced by precipitating insulin w/ Zn or protamine to form amorphous solid/insoluble crystals, injected into suspension from which insulin is slowly absorbed
What are the 4 principal types of insulin?
