Summary parenteral administration

Parenteral administration

Parenteral drug delivery
Sterile preparations intended for administration by injection, infusion or implantation into
the human or animal body
› Injections
› Infusions
› Concentrates for injections or infusions
› Powder for injections or infusions
› Gels for injections
› Implants

When parenteral administration?
- Patient unable to take drug orally
- No oral or rectal dosage form of the API available
- Poor absorption from the gastrointestinal tract or other routes of administration
 Physicochemical properties API, disease, proteins
- Rapid and sufficiently high concentration in the body is necessary
- High concentration necessary not achieved by tablet or suppository
- Continuous administration necessary for constant blood level
 Steady state
- Most precise way of administering
 Most suitable for narrow therapeutic window drugs

Disadvantages:
- expensive production
- poor stability of API in solution (add excipients)
- API not resistant to sterilization
- Risk of infection
- Risk of tissue damage at site of injection
- Needle fear
- Mistakes at time of administration, side effects or hypersensitivity may cause damage
- Administration demands knowledge and skills
- Injected air may elicit embolism
- Infusion: obstruction and biofilm forming (bacterial growth in line  infection)
- Infusion: limited mobility patient
- Infusion: application labour-intensive

Parenteral routes
1. Subcutaneous (under the skin) 0.1-2 mL (>2 discomfort)
2. Intramuscular (in a muscle) 0.5-10 mL
3. Intravenous (in a vein) 1-5000 mL

Injection or infusion?
Injection
- Limited volume (Max 10 mL)
- Drugs with longer elimination half-life

, Infusion
- Drugs with shorter elimination half-life
- Continuous blood level
- Larger volumes
- Limits patient’s mobility
- Toxic and strongly irritating drugs
- Parenteral nutrition

Plasma-time curves
- oral: drug dissolves in intestinal fluid, absorbed in membrane
- intravenous: immediate effect, API given to the patient is AUC, 100%
- <100%  first pass-effect

Biopharmaceutics parenteral route
- Rapid action
 API in solution
- Prolonged action
 Intramuscular
 API as suspension
 API in implant/gel
 Less water-soluble derivative of API
 API in advanced formulation
 E.g., microspheres

Side effects
Faster and more intense than after enteral or cutaneous administration. Rapid
intervention may be necessary.

Protein drugs
- Immunological reactions (hypersensitivity)
 Aggregates: foreign proteins (immune-system developing  allergic
reaction)
 Non-human components

Phlebitis
- too high/low pH or afwijkende osmotic level  inflammation blood vessel

Pain caused by needle fear

Extravasation
Inject next through a vessel  necrosis / gsngrene

Particles
- glass, rubber (file / rubber stopper of a file)

Requirements