Parenterals

Question 1

Advantages of parenteral administration

Answer 1

• Viable in emergency
• Provides accurate dosage
• Localized effect
• Fastest action
• Prolonged action
• alternative to other routes of delivery
• avoid GI enzymatic degradation and instability
• avoid low and variable absorption

Question 2

Disadvantages of parenteral administration

Answer 2

• Painful
• Need trained personnel to administer
• Rapid action -> difficult to reverse drug’s effects
• Needle problems
• High cost of manufacturing
• Strict packaging requirements

Question 3

Routes of parenterals administration

Answer 3

• subcutaneous (SC) - injection beneath the surface of the skin in small amounts 1.3 mL
• intravenous (IV) - rapid action, accurate, lifesaving in emergency
• intramuscular (IM) - drug action is less rapid but of greater duration compared to IV route, injected in skeletal muscles away from major nerves and vessels
• intradermal

Question 4

Official types of injections

Answer 4

• Injection: liquid preparations that are drug solutions/substances (e.g. insulin injections); dry solids/concentrate -> need addition of solvent
• Injectable emulsion (can be injected in muscles but not in veins): drug dissolved/dispersed in an emulsion medium (e.g. Propofol)
• Injectable suspension: Preparation of solids in a liquid medium (e.g. Methyl prednisolone acetate suspension)

Question 5

Characteristics of parenterals

Answer 5

• sterile
• pyrogen-free
• particulate free

Question 6

Requirements for solutions and suspensions to be used for injections

Answer 6

• solvents/vehicles must meet purity and safety standards
• Must be sterile and pyrogen-free
• Must be prepared under aseptic conditions
• Restrictions on buffers, stabilizers, antimicrobial preservative
• Coloring agent strictly prohibited
• Must meet standards for particulate matter
• Packaged in hermetic containers of specific and high quality
• Filled in slight excess for easy withdrawal
• Sterilized powders intended for solutions/suspensions are packed as lyophilized/freeze-dried powders
• Specific labeling regulations apply

Question 7

What is lyophilization (freeze-drying) and its steps?

Answer 7

Process of drying in which water is sublimed from the product after it is frozen

1. Freezing an aqueous product
2. Evacuate the chamber
3. Introducing heat to the product to allow for subliming of ice into a cold condensing surface

Question 8

Ingredients for parenterals

Answer 8

• Vehicle
• buffers
• antioxidants
• antibacterial agents
• tonicity materials: dextrose, glycerin, mannitol, NaCl
• Surfactants: egg and soybean phospholipids and lecithin
• thickeners
• preservatives: multidose containers
• Solubilizers, protectants, wetting agents emulsifiers, local anesthetics

Question 9

Ingredients for parenterals: Types of Vehicles

Answer 9

• Aqueous vehicles: water most frequently used and preferred (E.g. water for injection USP/Purified water USP, sterile water for injection USP, bacteriostatic water for injection USP, sterile water for irrigation)
• Water-miscible vehicles: increase drug solubility and/or reduce hydrolysis -> stability (e.g. ethanol, propylene glycol, polyethylene glycol 300)
• Non-aqueous vehicles: pure sterile, must remain clear on cooling to 10C, use is confined to IM injections, can be irritating and allergic reactions can occur (e.g. peanut oil - dimercaprol, cotton seed oil - estradiol cypionate, castor oil - estradiol valerate)

Question 10

Ingredients for parenterals: Buffers

Answer 10

• Maintains pH, stability and prevent degradation
• Blood pH 7.4
• e.g. monosodium phosphate/disodium phosphate -> pKa 7.21
• e.g. disodium citrate/trisodium citrate -> pKa 6.4

Question 11

Ingredients for parenterals: Antioxidants

Answer 11

• Prevent the oxidization process by blocking the oxidization process or being oxidized faster than the drug
• air is displaced with inert gas (N2) -> prevent chemical reactions
• e.g. (water-soluble): ascorbic acid, sodium sulfite, sodium bisulfite, (oil-soluble): butylated hydroxytoluene and hydroxyanisole

Question 12

Ingredients for parenterals: Antibacterial agents

Answer 12

• prevent microbial growth and multiplication
• use limited concentration
• effectiveness varies with formulation
• refrigeration slow the growth but does not prevent it

Question 13

How to determine the effectiveness of an antimicrobial system for a parenteral

Answer 13

1. Inoculums containing a known number of organisms (Candida albecans, Aspergillus niger,..) is added
2. incubate at 32C for few days
   - > Result: adequate if no significant rise in microorganisms

Question 14

Ingredients for parenterals: Tonicity agents

Answer 14

• routes that require isotonicity: intrathecal, intraarticular, intradermal
• decrease pain of injection and tissue irritation
• decrease hemolysis of blood cells
• prevent electrolyte imbalance
• can include buffers: sodium chloride (0.9%), potassium chloride, dextrose (5.5%), mannitol, sorbitol, lactose

Question 15

Ingredients for parenterals: Protectants

Answer 15

• Sugars that form glasses at low temp
• Used to maintain the chemical and physical stability of drugs that are frozen and freeze-dried: protein drugs and some peptide antibiotics

Question 16

Other parenteral adjuncts

Answer 16

• suspending/viscosity increasing agents: sodium carboxymethyl cellulose, gelatin, methylcellulose
• Chelating agents: ethylenediamine tetraacetic acid
• Inert gases: N2, CO2
• Adjuncts influencing solubility: sodium benzoate to solubilize caffeine, ethylene diamine to solubilize theophylline

Question 17

Aseptic procedures use

Answer 17

• UV lights
• Filtered air supply
• Sterile equipment

Question 18

Packaging of injections

Answer 18

• Packaged to maintain product sterility until time of use
• containers must not interact with the preparation
• types of containers: glass and plastic polymers
• plastic bags
• dual chamber vials
• cartridges and delivery pens

Question 19

Parenteral Incompabilities

Answer 19

• Physical - visible change in solution appearance e.g. precipitation, color, gas formation
• Chemical - chemical change -> toxicity/therapeutic inactivity (not always visible) - hydrolysis, complexation, oxidation, photolysis
• Therapeutic - change in activity e.g. cortisone antagonizing heparin

Question 20

Available injections

Answer 20

1. Small volume parenterals (SVP) - 25-50 ml
   - Can be in solution/suspensions, emulsions, solids
   - premixed, ready to use -> require little/no manipulation
   - Little wastage
   - do not offer flexibility in quantity/concentration
   - some products require thawing -> microwave
2. Large volume parenterals (LVP) - 100 ml - 1L or more per day
   - Flexible but requires manipulation
   - Usually administered by IV infusion to replenish body fluids, electrolytes, or to provide nutrition
   - Should not contain bacteriostatic/pharmaceutical additives
   - Contain electrolytes, carbohydrates, proteins, fatty emulsions

Question 21

LVPs is employed for

Answer 21

• Maintenance therapy: For patients entering/recovering from surgery and for those who are unconscious and unable to take nutrients;
  Total parenteral nutrition (TPN) provided if oral feeding must be differed for period of weekls/longer to provide all essential nutrients to minimise tissue breakdown and maintain normacy;
  Total nutrient admixtures (TNA) include all substrates necessary for nutritional support (carbohydrates, proteins, fats, electrolytes and trace elements)
• Replacement therapy: heavy loss of water and electrolytes need to be replaced; for patients with vomiting, diarrhea…

Question 22

What are irrigation solutions

Answer 22

• intended to bath/wash wounds, surgical incisions or body tissues (during operations)
• subjected to same stringent standard as for parenteral preparations
  e. g. sodium chloride irrigation, USP 0.9% NaCl used to wash wounds and employed as enema

Question 23

What is dialysis

Answer 23

Separation of substances from one another in solution by taking advantage of their differing diffusibility through membranes

Question 24

What does dialysis solutions usually contain

Answer 24

• Dextrose
• Vitamins
• Electrolytes
• Amino acids