Injections I

• Enteral administration

  Drug administration via the alimentary canal, either oral or rectal
• Parenteral administration

  Drug administration that doesn't use the alimentary canal, it takes the drug directly into body fluids, bypassing the GI membranes
• Parenteral routes

  • Intravenous
  • Intramuscular
  • Intradermal (subcutaneous)
  • Intra-arterial
  • Intracardiac
  • CNS injections (intraspinal, intra-ventricular, etc.)
  • Intra-articular
  • Ophthalmic injections (subconjunctival, intra-vitreal, etc.)
• Parenteral administration

  • Provides more predictable blood levels than oral dosage forms
• IV injection (bolus dose)

  Rapidly increases the concentration of the drug in the plasma and produces a very rapid effect
• IV infusion

  Allows the drug to enter the circulation at a much slower and controlled rate
• IV injection (bolus dose)

  Rapid onset of action, but peak blood levels may not be achieved for 12 hours after oral administration
• IV administration

  • Allows precise dosing at a controllable rate
  • Sterility required
• IM injection

  Delivers the drug into the tissue of a relaxed muscle, allowing delayed and prolonged release into the circulation
• IM injections

  • Deliver exact amounts of drug whilst allowing site control over the rate of absorption
  • Aqueous or oily solutions or suspensions can be administered in volumes up to 4 mL
• Factors affecting rate of IM absorption include blood supply of the muscle, massage, ionization of drug and type of formulation
• Subcutaneous injection

  Administered into the loose connective tissue and adipose tissues immediately beneath the dermal skin layer

  
• Subcutaneous injections

  • Volumes of up to 1 mL can be administered
  • Aqueous solutions or suspensions of drugs are administered by this route
  • Absorption is slower than IM due to less vascularity
• Drugs administered by subcutaneous route

  • Epinephrine
  • Insulin
  • Heparin
• Subcutaneous injections are more painful than IM due to greater number of nerves
• Subcutaneous tissue

  • Has less blood vessels than muscle tissue
  • Drugs are absorbed more slowly
  • Effects are prolonged
• Drugs administered by subcutaneous route

  • Epinephrine
  • Insulin
  • Heparin
• Subcutaneous route

  Drug injected into alveolar connective tissue just below skin surface

  
• Subcutaneous route

  Absorption slower than intramuscular route generally (but may be prompt with certain drugs)
• Subcutaneous route has a slower rate of absorption compared to intramuscular route
• Vehicles

  Substances used to dissolve or dilute parenteral products before administration
• Water for injections

  • High level of chemical purity
  • Well-tolerated by the body
  • Solvent for a wide range of drug substances
  • Pyrogens-free
• Preparation of sterile water for injections

  1. Distillation of potable water

  2. Chemical softening and filtration

  3. Deionization and pH adjustment

  4. Reverse osmosis and distillation
• Non-aqueous solvents

  Used to improve solubility of drugs that are poorly soluble in water
• Non-aqueous solvents

  • Ethanol
  • Glycerol
  • Propylene glycol
• Solubilising agents

  Added to injection formulations to aid dissolution of drugs with poor aqueous solubility
• Solubilising agents

  • Polyoxyethylene castor oil derivatives
  • Cyclodextrins

  
• Oil-in-water emulsions

  Used to administer water-insoluble drugs parenterally
• Oils used in oil-in-water emulsions

  • Arachis oil
  • Sesame oil
• Oil-in-water emulsions

  • Droplet size must be controlled (usually less than 3 μm in diameter) to prevent oil embolisms
• Antimicrobial agents

  Added to multi-dose vials to inhibit growth of microorganisms introduced during repeated use
• Antimicrobial agents

  • Benzyl alcohol
  • Cresol
  • Phenol

  
• Antimicrobial effect of excipients

  • Ethanol (above 10% v/v)
  • Glycerol (10-20% v/v)
  • Propylene glycol (15-30% v/v)

  
• Antimicrobial agents should not be added to large volume parenteral products (infusions) or products intended for intraspinal or intraocular injection
• Antioxidants

  Chemicals with lower oxidation potential than the drug substance, react with oxygen to prevent drug degradation
• Chelating agents

  Enhance the activity of antioxidants by removing trace metal ions that catalyse oxidation
• Chelating agents

  • EDTA
  • Citric acid
• Buffers

  Maintain the pH of parenteral products at the desired optimum value
• Ideal pH of parenteral products is 7.4 to match physiological pH
• pH adjustment

  • Acidifying agents (e.g. hydrochloric, citric, sulfuric acids)
  • Alkalising agents (e.g. sodium bicarbonate, sodium citrate, sodium hydroxide)