Why are more and more drugs being administered parenterally?
- Clinical need in particular medical situations for rapid, assured high blood and tissue levels
- Oral administration
> Very inefficient or unreliable absorption from the GIT
> Destruction or inactivation in the GIT
> Extensive mucosal or first-pass metabolism following oral administration
Provide FOUR advantages of Parenteral Route of Drug administration
- Rapid onset
- Predictable effect
- Predictable and nearly complete bioavailability
- Avoidance of the gastrointestinal tract (GIT), hence the problems of variable absorption, drug inactivation, and GI distress
- Reliable drug administration in very ill or comatose patients
Provide THREE disadvantages of Parenteral Route of Drug administration
- Frequent pain and discomfort of injections
- Psychological fears associated with “the needle”
- Incorrect drug or dose is often harder or impossible to counteract when it has been given parenterally rather than orally
How to define parenteral preparations?
Parenteral preparations are sterile preparations intended for administration by injection, infusion or implantation into the human or animal body
What are some quality aspects of parenteral dosage forms?
- Pyrogen free
- Sterile
- Free from visible particulate matter
- Container-closure integrity
- Injection site tolerability
- Physical and chemical stability
- The formulation containing the fewest number and the simplest excipients possible
- Highest level of purity for the active drug substance and excipients
- Detailed dosing and administration instructions including evaluation of compatibility with coadministered drugs
What are the types of injections? How are they prepared?
Solutions, emulsions or suspensions. They are prepared by dissolving, emulsifying or suspending the active substance(s) and any added excipients in Water for injections, in a suitable, sterile non-aqueous liquid or in a mixture of these vehicles
For solutions, emulsions, and suspensions (types of injections)
A) Which one is used for injections and do not show any evidence of phase separation?
B) Which one for injection may show a sediment which is readily dispersed on shaking to give a suspension which remains sufficiently stable to enable the correct dose to be withdrawn?
C) Under suitable conditions of visibility, are clear and practically free from particles
A) emulsions
B) suspension
C) solutions
What are the FIVE official types of injections?
- [Drug] Injection
- [Drug] for Injection
- [Drug] Injectable Emulsion
- [Drug] Injectable Suspension
- [Drug] for Injectable Suspension
What does the physiochemical properties of the drug depend on?
If the dosage form is a SOLUTION, SUSPENSION,EMULSION or POWDER
What are the excipients used in injections?
- Vehicle
- Buffering agent
- Solubilising agent and surfactant
- Preservative
- Antioxidant
- Chelating agent
- Inert gas
- Protectant
- Tonicity adjustment agent
What are the SEVEN factors/criteria to consider when creating a basic formulation of injection?
- Volume
- Vehicle
- Stability
- Tonicity
- Preservative
- Sterility
- Safety
What is volume dependent on? When must volume be made isotonic?
- Usually depends on the solubility of the medicament (active ingredient)
- Route of administration
- The volume also influences other aspects of formula
> LARGE VOLUME must be made isotonic
- IV injections of doses greater than 15mL may not contain a bactericide
What are the routes of parenteral administration?
- Subcutaneous route
- Intramuscular route
- Intravenous route
- Specialised route –> intradermal, intrathecal, intracardiac, intra-articular
For Intravenous route (IV route);
A) What is the volume required
B) Where is it injected
C) Benefit of it?
D) Danger of it?
E) What will a rapid drug administration do?
F) Where is risk of thrombosis increased
A)
- 1mL or less to 500mL or even more
B)
- Injected directly to the vein
- Immediate total access to bloodstream
C)
- Extremely rapid and predictable response, avoid irritation to other tissue
D)
- Antidoting very difficult, if not impossible, in most cases
E)
- May cause drug shock (excessive drug concentration at the target organ)
F)
- Increased at extremity sites (wrist or ankle) or patients with impaired circulation
For intramuscular route (IM);
A) Volume required?
B) Where are the injection sites?
C) Why is the drug slowly absorbed?
D) How can it be controlled to produce long-acting products?
E) What can result from faulty technique?
A)
- Rarely greater than 2mL, should not exceed 4mL at one site
B)
- Principal injection sites are the gluteal (buttocks), deltoid (upper arm), and vastus lateralis (lateral thigh) muscles
C)
- Forms a depot in the muscle mass
D)
- Dissolution and absorption
E)
- Muscle or neural damage
For the subcutaneous route;
A) What is the volume required?
B) Slower onset of action than the ….. routes?
C) Where are the injection sites?
D) What can irritating drugs and vasoconstrictors lead to?
A)
- 1 mL or less
B)
- IV/IM routes
- Total absorption may be less
C)
- Most portions of the arms and legs plus the abdomen
D)
- Can lead to abscesses, necrosis or inflammation
What is the volume required for the intrathecal route? Where is the injection site? What drugs use this route?
Usually less than 20mL
- Injection into the subarachnoid space that surrounds the spinal cord
- The route is used for spinal anaesthetics and antibiotics
For the intrathecal and epidural route of parenteral delivery
A) What are the similarities between the two?
B) What are the differences between the two?
A)
- Intrathecal and epidural drug delivery comprises the intraspinal routes of drug administration
- Each route delivers drug to the cerebrospinal fluid (CSF)
B)
- Intrathecal delivery involves the direct injection of the drug into the CSF –> intrathecally administered drugs are confined within the CSF
- Drugs injected in the epidural space have to cross the dura membrane in order to reach the CSF –> epidurally administered drugs can also reach the systemic circulation
For the intradermal route;
A) What is the volume required
B) What is the injection site?
C) Why is it used?
D) Why must ID injections be of very small volume
A)
- Usually 0.1-0.2 mL
B)
- Made into the skin between the dermis, and epiderms
C)
- Used mainly for diagnostic purposes in investigations of immunity and allergy
D)
- Do not disperse quickly from their relatively non-vascular site and even a fraction of a milliliter remains as a small blister for some time after injection
What considerations are required when choosing a vehicle for parenteral formulation?
- Drug solubility
- Route of administration
- Dosage form
- Aqueous vehicles –> water for injection
- Non-aqueous vehicles –> oil, alcohol, propylene glycol
For the stability criteria, how can hydrolysis and oxidation of the active ingredient be reduced?
- Vehicle (co-solvent)
- pH control with buffering agents
- Antioxidant
- Inert gas
- Amber glass container –> protect from light
- Powder for injection formulation
A drug is hypertonic when it draws water out from cells
A drug is hypotonic when water moves into cells
A) What tonicity is required for IV injection?
B) What tonicity is required for IM injection?
C) What tonicity is required for subcutaneous injection?
D) What tonicity is required for intradermal injection?
E) What tonicity is required for intrathecal injection?
A)
- Isotonic is always desirable
- If hypotonic –> should be rendered isotonic
B)
- Can be slightly hypertonic to promote absorption
- Aqueous depot formulation should not be made hypertonic (will increase absorption)
C)
- Isotonicity although desirable is not essential (injected into fatty tissue and not into the bloodstream)
D)
- Should be isotonic since a paratonic solution might cause a false reaction
E)
- Must be isotonic
- The volume of CSF only 60-80mL, a small volume of paratonic solution will disturb the osmotic pressure and may cause vomiting and other effects
For the preservation criteria, what are some common causes of contamination during aseptic compounding?
- Failure in the sterilisation of the cap; from using an ineffective antiseptic or not allowing sufficient time for bactericidal action
- Bacteria settling on the cap
- Failure in the sterilisation of the needle or syringe
- Injection of unsterile air
- In rush of unsterile air as the needle is withdrawn
When is a preservative agent required? Provide TWO instances
Injections sterilised by filtration
- Requires a very high degree of manipulative skill to prevent accidental contamination of the solution
- Addition of a suitable bactericide before filtration is allowed but not obligatory
Multiple-dose container
- A multiple-dose container is a hermetic container that permits withdrawal of successive portions of the contents without changing the strength, quality, or purity of the remaining portion
- Antibacterial additive is required
Not required in a single dose container that will be sterilized terminally
