LEC4 parental route of administration

• Parenteral


  Located outside the alimentary canal, taken into the body or administered in a manner other than through the digestive tract, as by intravenous or intramuscular injection
• Types of parenteral formulations

  • Injections
  • Solutions
  • Emulsions
  • Suspensions
  • Liposomes
  • Microspheres
  • Nanosystems
  • Powders to be reconstituted as solutions
• Parenteral formulations


  • Sterile - free of microorganisms
  • Pyrogen-free
  • Isotonic
  • Free from visible particulate matter
  • Stable - chemically, physically and microbiologically
  • Compatible with other sterile diluents and co-administered drug(s)
• Parenteral formulations are usually solutions or aqueous emulsions (in which the size of the disperse phase is small)</b>
• Water in oil emulsions or suspensions should not be administered by the IV route
• The rate of administration must not be too quick to avoid an excessive concentration of drug at the target organ
• Intravenous (IV) administration


  • 100% bioavailability compared with other routes
  • Fastest and most certain parenteral route
  • Rate of administration can be controlled (rapid onset or controlled over time)
  • Suitable for medicines that degrade orally
• Disadvantages of IV administration

  • Any side effects will occur rapidly
  • Some medicines must be administered very slowly with constant monitoring
  • Aseptic technique is essential
  • Increased risk of infections/complications
• Intramuscular (IM) administration


  • Small volumes only (1.5ml - 5ml)
  • Relatively rapid absorption
  • Systemic effects within 15 to 30 minutes
  • Often used for controlled release formulations
• Factors affecting IM drug absorption

  • Vascularity of muscle site
  • Drug's lipid solubility
  • Vehicle in which drug is contained
  • Injection technique and depth of needle
• Disadvantages of IM administration

  • May be painful
  • Expensive
  • Hard to retrieve once administered
  • Difficult to self-administer
  • Atrophy if given repeatedly
• Subcutaneous (SC) administration


  • Usually small volumes (up to 1ml)
  • Hypodermoclysis (large-volume electrolyte or dextrose solutions, up to 1000 ml)
  • Syringe drivers
  • For non-irritating drugs only
  • Well vascularised, fairly rapidly absorbed
  • Slower onset of action and sometimes less total absorption compared to IV or IM
• Factors affecting SC drug absorption

  • Vascularity of site
  • Drug's lipid solubility
  • Vehicle in which drug is contained
• SC formulation examples


  • Insulin
  • Low Molecular Weight Heparins (e.g. enoxaparin)
  • Zoladex (goserelin)
• Intradermal administration


  • Between the epidermal and dermal skin layers
  • Very small volumes only (up to 0.2ml)
  • Absorption rate is very slow
  • Used for immunological tests

  
• Intrathecal administration


  • Injection of a drug into the cerebrospinal fluid (CSF)
  • Volumes up to 10ml
  • Used for substances that do not cross the BBB, cerebral infections/tumours, anaesthesia

  
• Intra-osseous administration


  • Administration into the bone marrow
  • Emergency or short-term treatment when access by the vascular route cannot be achieved and the patient's condition is considered life threatening (infants and children)
• Intra-articular administration


  • Administration into the synovial fluid of joint cavities
  • E.g. knee for arthritis/sports injuries

  
• Intracavernosal administration of alprostadil

  • Along the dorsolateral aspect of the proximal third of the penis (visible veins should be avoided)
• Direct urethral application of alprostadil

  • Administered to the urethra
• Oral route is the most common and widely accepted route of administration
• Advantages of oral route

  • Safest, more convenient and economical than parenteral route
  • Self-administration is possible
  • Drugs with range of physiological properties can be delivered
• Disadvantages of oral route

  • Destruction of the drug due to pH, bile, enzymes in GI tract
  • Variable absorption across the GI tract
  • Patient co-operation and compliance required
  • Emesis
  • First pass metabolism for some drugs limits bioavailability
• Advantages of parenteral (injection) route

  • Avoidance of pre-systemic and first pass metabolism - increased bioavailability
  • More rapid and predictable absorption - more accurate selection of the effective dose
  • Local effects may be achieved
  • Important in emergency therapy, uncooperative patients, swallowing difficulties, emesis
• Disadvantages of parenteral (injection) route

  • Painful - poor patient compliance, needle phobia
  • Expensive, strict control of environment during manufacturing, storage and handling required - aseptic controlled environment is essential
  • Difficult to self-medicate, need skilled people to administer
  • Difficult to reverse the effects of drugs
• Needles and administration technique are important considerations for parenteral routes
• The correct parenteral administration site matters and can impact the effectiveness and safety of the drug
• Pharmaceutical queries for IV drug administration

  1. Dose check

  2. Reconstitution and displacement values

  3. Incompatibilities

  4. Appropriate diluent

  5. Dilution factor

  6. Flushing the line

  7. Infusion rate

  8. Duration of infusion

  9. Mixing with other diluents
• Calculating displacement values


  Determine the volume occupied by the powder when reconstituted
• Isotonic solution


  Has the same osmotic pressure as a body fluid
• Hypotonic solution


  Has lower osmotic pressure than a body fluid, leading to swelling and bursting of red blood cells
• Hypertonic solution


  Has higher osmotic pressure than a body fluid, leading to shrinkage of red blood cells
• Freezing point depression method for calculating isotonicity


  Determine the freezing point depression of the solution and adjust with an appropriate substance (e.g. sodium chloride, glucose) to match the freezing point depression of body fluids (0.52°C)