parenteral routes for administations
-intravenous IV: least forgiving, rug must be dissolved
-intramuscular IM
-subcutaneous SC
-intradermal
-intraperitoneal IP
-intraspinal: very delicate
IV
-intravenous
– Very rapid
– Straight to the blood
– Good for irritant drugs
– Suitable for large volumes
common aqueous isotonic vehicles
-0.9% (w/v) NaCl Solution
AKA Normal Saline (NS) or Saline
-5% (w/v) Dextrose Solution
AKA D5W
-Bacteriostatic Sodium Chloride Injection
Normal Saline with antimicrobial preservative(s)
-Ringer’s Solution
Normal Saline with K+ and Ca2+ in approx.
physiological concentrations
water miscible solvents
- PEG can be used IV at concentrations as
high of 40% (v/v) - Ethyl alcohol can be used up to ~10% (v/v)
components of parenteral products vehicles
- Water miscible solvents (cosolvents)
– Ethyl alcohol
– Polyethylene glycol (PEG)
– Propylene glycol (PG) - Used to solubilize drugs
- Can also slow down hydrolysis reactions
- Often for intramuscular injection
- But also used in IV preparations
what about oils?
- Straight liquid oil injected into veins (IV) is a BIG
NO-NO
– It is effectively an embolus - Oil emulsion is OK for IV injection
– Oil is distributed into small droplets that are even smaller than red blood cells
– No risk of embolism
– Solution Emulsion - Oil-based solutions for IM injection are acceptable and do exist
do not get confused
- Oil solution does not equal Oil emulsion
- Oil solutions (oil as the solvent) must not
be injected directly into veins - An emulsion contains oil, but it is not oil
- Some emulsions (e.g., PN, parenteral nutrition)
are administered by the IV route
components of parenteral products antimicrobial preservatives
- Used for multiple dose preparations
- Benzyl alcohol 0.9% is the most common preservative
- Parabens: combination of methyl and propyl-parabens, 0.18% and 0.02%, respectively*
- Cresol
- Antimicrobials are not very effective in non-aqueous (oil based) formulations
- Compatibility Issues
– Some excipients inactivate (“sequester”) antimicrobial preservatives. Examples: Polysorbate (through micelles) and PVP (complex-like formation)
only preparations intended for multiple use are allowed to contains _________
antimicrobial preservatives
preparations intended for multiple use must ____-
contain an antimicrobial preservative
moral of the story about antimicrobial preservatives
- If you are going to be punching holes in a
sterile container to administer the drug
contained in it more than once, you better
have some antibacterial preservative in it - Any sterile product intended for multiple
dose use must contain antibacterial
preservative - Single dose = single use. Preparations are
single use containers. Period
preservatives- remember
- Benzyl alcohol 0.9% is the most commonly used
antimicrobial preservative - It is generally safe to use, but
- Some people are allergic
- DO NOT use Benzyl alcohol in neonates. It can
produce gasping syndrome - Do no use preparations containing antimicrobial
preservatives in neonates - Preparations intended for the intra-spinal route of administration must be free of antimicrobial
preservatives
pH buffers
– Why have them in a parenteral product?
– To address solubility and/or stability issues with the drug
– Use them at as low concentration as necessary
– Commonly used buffers:
– Citrates – some caution. Safe by IV, very irritating by IM or SC routes
– Acetates
– Phosphates – considerable caution. Potentially fatal danger
compounding sterile preparations pH buffers
- Buffered vs. unbuffered formulations
- Buffers are used to “force” the pH to
remain at a fixed value - Unbuffered solutions are quickly diluted
into physiological pH - That is why you want buffers as dilute as
possible*, so the physiological pH takes
over asap
antioxidants components of parenteral products
– Metabisulfite salts – low pH
– Bisulfite – intermediate pH
– Sulfite – high pH
– Ascorbic acid
_____ injected by the IM or SC routes can be very irritating but can be injected intravenously without problems
citrate
______ and _______ need to be given together in PN preparations. when they are combined they have a strong tendency to precipitate and the result can be fatal
phosphate and calcium
chelating agents: components of parenteral products
– Most common Sodium EDTA
– Enhance antioxidant’s effect
– Sequester trace metals
components of parenteral products tonicity agents
-normal saline
-D5W
-glycerol
-is isotonic
-has physiological pH
