Section 7 - Parenterals 2 Flashcards
What are large volume parenterals packaged in?
Glass or plastic
Are large volume parenterals preserved?
Never
What are large volume parenterals primarily used for?
Volume and electrolyte replacement by IV route
What is the volume of large volume parenterals for IV solutions?
100-1000 mL
What is the normal daily intake of water for adults?
50 mL/kg
What are the most common components in fluid replacement?
Sodium chloride and dextrose
What is an example of a hypotonic, isotonic, and hypertonic fluid replacement?
- Hypotonic = 0.45% sodium chloride
- Isotonic = 0.9% sodium chloride
- Hypertonic = D10W
How are electrolyte solutions available?
In concentrates, which must be diluted and added to large volume parenterals
What are electrolyte solutions used for?
- Electrolyte deficiency
- Restore pH balance
Why is sodium lactate used for acidosis?
Lactic acid is used in the Kreb’s cycle, which produces CO2, which turns into carbonate to help w/ acidosis
What are 2 examples of drugs that require a loading dose?
Heparin and lidocaine
Is sodium chloride or dextrose a better option to hydrate a person and why?
Dextrose b/c will be metabolized through the Kreb’s cycle
What is mannitol 10% or 20% used for?
Osmotic diuretics as an infusion
What is sodium carbonate 5% used for?
Treatment of acidosis
What is alcohol 10% in dextrose used for?
Methanol or ethylene glycol intoxication
What is the function of dextrans?
Plasma expanders
Which blood products are given as LVP?
Albumin, fresh-frozen plasma, whole blood
When can large volume parenterals exceed 1000 mL?
- LVP-like products that are not meant for IV administration
- Peritoneal dialysis solutions, parenteral nutrition solutions, irrigation solutions
What must be determined when preparing a small volume parenteral?
- Route of administration
- Selection of vehicle
- Required added substances
- Appropriate container and closure
What is the volume for IM injections?
Below 10 mL
Which route shouldn’t be used if drug requires prolonged release?
IV
What are the most common vehicles used for SVP?
Aqueous, aqueous w/ co-solvents, or non-aqueous
Which vehicle is most desirable for SVP?
Aqueous, but drug solubility may be an issue
Which co-solvents are used w/ non-polar substances to increase water solubility?
Alcohol, glycerol, propylene glycol, or polyethylene glycol
What are the uses of co-solvents?
- Increase solubility
- Prevent chemical degradation
What are some disadvantages to co-solvents?
- Tissue irritation (if given IM)
- Dilution may cause drug to come out of solution
- Potential toxicities if given in large dose
What is another way to increase solubility besides co-solvents?
Non-ionic surfactants (ex: span, tween, cremophor, labrasol)
What are the common concentrations of surfactants?
0.05-0.5%
Why are ionic surfactants not generally used?
Irritation or damage to membranes
What must be evaluated when using surfactants?
Safety, tissue tolerance, and hemolytic activity
What do surfactants do at low concentrations?
Can adsorb to the surface of the drug molecule and give the drug some polar properties
What do surfactants do at high concentrations?
May orient into concentrated polar and non-polar centres and form micelles
What are cyclodextrins?
Oligomers of glucose
What do cyclodextrins do?
- Can exert solubilizing effect by forming stable inclusion complexes
- Amphipathic w/ exterior being hydrophilic while interior is hydrophobic
Which cyclodextrins can be used for parenterals?
Modified or substituted
What effect does an oil vehicle have on drug solubility?
Metabolizable vegetable oils may increase drug solubility
Oily injections are intended for ____ use
IM
Can oils provide prolonged/sustained release?
Yes
Which substances are often added to parenterals to improve efficacy, elegance, and stability?
- Buffers
- Antioxidants
- Antimicrobial agents
- Tonicity adjusters
What are buffers used for in parenterals?
- Enhance stability and/or solubility
- Resist pH changes on storage
What can pH above 9 cause?
Tissue necrosis
What can pH below 3 cause?
Pain and/or phlebitis
What are common buffers used in parenterals?
Citrate, acetate, phosphate, and tromethamine
What effect does citrate on thiamine (vitamin B1)?
Increases degradation rate of thiamine
What effect do phosphates have on phenethicillin?
Increases degradation of phenethicillin
What effect do phosphates have on citrate?
Calcium will precipitate
What is buffer capacity?
Number of moles of strong acid/base which has to be added to 1000 mL of buffer to cause a change of 1 pH unit
How can you make a drug less vulnerable to oxidation?
- Lowering pH by addition of H ions
- Chelating agents
- Protection from light
- Replacement of air w/ inert gas
- Slightly acidic pH
- Addition of antioxidants
What do antioxidants do?
Have higher oxidation potential than the drug, so are preferentially oxidized
What are common antioxidants used in parenterals?
Bisulfites and ascorbic acid
When can antioxidants not be used?
- LVPs, intrathecal, or intraocular injectables
- Avoided or used w/ caution in young children
What do bisulfites react w/?
- Formation of insoluble salts when bisulfites oxidize to sulfate
- Bisulfate reacts w/ aldehyde functional groups
Antimicrobial agents must be added to parenterals in _____
Multi-dose containers
When are antimicrobial agents not to be used?
- LVPs, intrathecal, or intraocular injectables
- Avoided or used w/ caution in young children
What must be done to ensure an effective concentration of antimicrobial agents is maintained?
- Must ensure packaging doesn’t adsorb to the point where the [ ] is ineffective
- Ensure no other component may inactivate the antimicrobial
What are some common antimicrobial preservatives used in parenterals?
Benzalkonium chloride, benzyl alcohol, parabens, phenol, and chlorocresol
What is the easiest way to determine quantity of tonicity adjuster needed?
Sodium chloride equivalent method
What is the easiest way to determine quantity of tonicity adjuster needed if the product is buffered?
White-Vincent method
What are examples of tonicity adjusters?
Sodium chloride, dextrose, mannitol, glycerol
What can be added if a product is hypertonic and is to be administered by IM route?
Local anesthetic (ex: benzyl alcohol)
What are the 4 categories for the antimicrobial effectiveness test?
1) Parenterals, ophthalmics, otics, sterile nasal products made w/ aqueous bases or vehicles
2) Topically used products w/ aqueous bases or vehicles; non-sterile nasal products; emulsions and products applied to mucous membranes
3) Oral products other than antacids made w/ aqueous bases or vehicles
4) Antacids made w/ aqueous base
What is done to the product during the antimicrobial effectiveness test?
Product in original container inoculated to provide 10^5 - 10^6 colony forming units per mL of product
When should the effectiveness of a preservative system be retested?
Any time the formulation is changed
What are the functions of containers for parenterals?
- Facilitate manufacture
- Maintain product integrity
- Allow inspection of product
- Permit shipping and storage
- Provide for convenient clinical use
What are the 3 types of glass recognized by the USP?
1) Borosilicate, least reactive (best but most expensive)
2) Soda lime glass treated w/ sulfate, sulfite, or sulfide to make it less reactive (used for products that remain below pH 7 during shelf life)
3) Soda lime glass untreated (used for dry powders which require reconstitution)
What container is usually used for products which are light-sensitive?
Amber glass
What is a disadvantage to amber glass containers?
Ions of iron or manganese can be extracted from the glass and function as catalysts for oxidation of the drug
What are rubber closures used for?
Parenteral products
What are some problems w/ closures?
- Leaching of materials into products
- Adsorption of product
- Particulate contamination from container/closure combination
Which physical properties are important in selection of closure?
- Compression set (good plastic/elastic properties to ensure leaf-proof fit)
- Flexibility
- Hardness (soft enough to allow easy passage of needle
- Resistance to passage of water vapor
- Resealability
- Tackiness (don’t want closures to stick together or clump)
Which plastics are used for packaging parenterals?
PVC and polyethylene
What are advantages to plastics?
Light weight, break resistant
What are disadvantages to plastics?
- Moisture and gas permeability
- Leaching
- Adsorption of drug material
