Topic 12 - Parenterals Flashcards
4 methods of administration by injection
- IV
- Intramuscular (IM)
- Subcutaneous (SC)
- Intradermal (ID)
Advantages of injection admin
- Rapid onset
- Predictable/complete bioavail in some cases
- Avoid problems in GI tract
- Reliable administration
Disadvantages of injection admin
- Costs (administration)
- Components need to be sterile
- Low pt compliance
List all admin injections in order of lowest-highest volume that can be injected
- id (0.2mL)
- sc (2mL)
- im (5mL)
- iv
What are the 3 forms admin injection can take?
- Solutions
- Suspensions
- Emulsions
*Also: coil dispersions
Pyrogen
Remnants from leftover bacteria. Most common example = lipopolysaccharaide from gram -ve bacterial cell walls
Why colouring agents not allowed in injection solutions?
Always a risk of -ve interaction w/ colouring agent and drug formulation
T/F: Salts can never be added to parenterals
F: Salts are added for tonicity so drug is injected into blood (restrictions)
Components of parenterals
- Water (injection)
- Active agent (solubility)
- Anti-oxidants (sacrificial, oxidize quicker than drug consumes O2 first)
- Buffers (maintains pH, drug stability, solubility, absorption. Goal: minimize pain, irritation and tissue necrosis)
- Chelating agents (remove residual metals from glass)
- Co-solvents
- Tonicity agents (semi-perm nature of cells and osmotic P solution)
- Preservatives
How can preservatives be made effective?
Make sure they break cell membranes, denature proteins, affect bacterial metabolisms
4 important criteria of preservatives:
- Effective
- Soluble
- Nonirritating, nonsensitizing, nontoxic
- Chemically stable
T/F: Most aqueous media are vulnerable to microorganisms
T
2 types of preservatives
- Antifungals
- Antimicrobials
what determines osmotic pressure?
Electrolytes
Osmotic activity is a _______ property (depends on # molecules present)
Colligative
Osmosis
Spontaneous net movement of solvent molecules through a semi-perm membrane from area of low solute concentration to high
Osmotic pressure
Minimum pressure to prevent the flow across semi-perm membrane
Tonicity
Extent of swelling or contraction of bioogical membrane
Describe hyper, hypo, and isotonic
Hyper = higher OP than cells, causes cells to shrink
Hypo = lower OP than cells, causes cells to rupture
Isotonic = same OP (want)
What happens to bpt and fpt when solute is added to water?
- Solute reduces escaping tendency of water - fewer solvent molecules at liq/gas interface, so less opportunity for solvent to vaporize (so bpt increases)
- Salt disrupts freezing point because it prevents water from making appropriate H-bonds to freeze (so fpt decreases)
Why do all solutions have the same Kb in water at ideally dilute sol’ns?
Ideally dilute = only water remaining essentially, so Kb sol’n = Kb water. The more concentrated the sol’n gets with the solutes, the further their properties deviate.
Van’t Hoff Factor (i)
Accounts for non-ideality, increased # of moles produced.
ie. if HCl is dissolved, there are i = 2 moles of solute, H+ and Cl-
NaCl Equivalent Method result
Calculates w/v % of NaCl to add to the solution so it becomes isotonic
White-Vincent/USP Method result
Calculates the volume in mL of isotonic sol’n that can be prepared by mixing drug with water/isotonic buffered solution. (w = wt, in g)
Freezing point depression method
Gives weight (w/v %) of reference salt (ie. NaCl) to add to the solution so it becomes isotonic
Buffers
Solutions that resist changes in pH on adding acid or alkali.
Buffer capacity
Measure of the resistance of a buffer sol’n to pH change
T/F: We want a solution with a strong buffering capacity so we have drastic pH changes
F: Formulation with a strong buffering capacity for pH will cause tissue damage. We want a weak buffering capacity
Criteria for good parenteral containers
- See-through
- Robust
- Sustainable (reduced waste)
- Does not affect contents
- Sterilized
- Provide light protection
- Cheap
3 compatibility issues with parenteral containers
- Leaching (something in container entering solution)
- Permeation
- Adsorption
As/Ds of plastic parenteral containers
A:
- Not breakable
- Light weight
- Flexible
D:
- Permeation (O2)
- Leachable plasticizers
- Drugs adsorption to plastic
- Difficult to sterilize
- Not very transparent
As/Ds of glass parenteral containers
A:
- Clear/transparent
- Impermeable
- Often reusable
- Easily sterilized
D:
- Breakable
- Leaching of metals
- May be rubber stoppers
What is freeze drying used for?
Dry heat-sensitive materials
Steps to freeze-drying
- Solution poured into vials, stopped, placed in trays
- Frozen by circulating fluid (ie. PEG, silicone oil) at -35ºC to -40ºC
- Pressure decreased below Pvap of water at that T
- Heat is applied by increasing temp of circulating fluid
Main issue with freeze drying
Proteins: if they aggregate, they are no longer active. Need to add sugars to prevent
As/Ds of freeze-drying
A:
- Degradation of product minimized
- Light, porous product
- No concentration of product during drying
D:
- Product is very hydroscopic
- Slow and expensive process
