Chapter 15 - Parenterals Part 2 Flashcards
name the 3 categories of nonaqueous vehicles for injections
-fixed oils
-water miscible susbtances
-other
name the requirements for fixed oils as nonaqueous vehicles for injection
-must be of VEGETABLE ORIGIN
-must be LIQUID at room temperature (unsaturated)
-not be free acids – causes muscle irritation
give 4 examples of fixed oils
corn oil
cottonseed oil
peanut oil
sesame oil
name 4 water miscible substances that are used as nonaqueous vehicles for injection
glycerin
polyethylene glycols
propylene glycol
alcohols
name the “other” nonaqueous vehicles for injection (not the fixed oils or water miscible substances)
they are used rarely
ethyl oleate
isopropyl myristate
dimthylacetamide
name 5 added substances to parenteral injections
the drug
isotonic agents
buffer agents
antimicrobial agents
antioxidants
the USP requires that 1 or more suitable substances be added to parenteral products that are packaged in ________ containers.
why?
multi-dose
to prevent the growth of microorganisms
name 2 isotonic agents
NaCl, dextrose
name 2 antimicrobial agents (preservatives)
thimerosal, benzyl alcohol
name 2 antioxidants used in parenteral preparations.
are they aqueous or oleaginous
sodium bisulfite
ascorbic acid
both aqueous
why are buffering agents used?
to prevent chemical degradation through hydrolysis,etc.
enhances stability
define sterility
the absence of life
define sterilization
the complete destruction of all viable microorganisms
what is a disinfectant
a substance used on inanimate objects to render them noninfectious
what is an antiseptic
a substance used to prevent sepsis
what is a pyrogen
a fever-producing substance
name 4 important considerations in sterilization
-the application of an adequate sterilization treatment
-verifying that the materials are sterile through the use of this treatment
-protect the sterile material
-delivery, opening, and use of the sterile material without entrance of contamination
name 5 methods of sterilization
-steam sterilization
-dry heat sterilization
-sterilization by filtration
-gas sterilization
-sterilization by ionizing raditiation
steam
dry heat
filtration
gas
ionizing raditation
what is the most RELIABLE method of sterilization to destroy all forms of microorganisms
steam sterilization
explain the method of steam sterilization and how it kills the bacteria.
called autoclaving – moist heat in the form of saturated steam under pressure
in the presence of this moisture, the bacterial proteins coagulate and get destroyed at a considerably lower temp than if moisture was not present
which are harder to destroy in steam sterilization – bacteria or spores?
explain
spores
bacterial cells have more moisture and are killed easier. spores have a relatively low percentage of water so are more difficult to destroy
what is the purpose of applying pressure in steam sterilization? what actually kills the microorganisms?
the purpose of applying pressure is simply to raise the temperature, not for the actual purpose of applying pressure
the temperature destroys the microorganisms, not the pressure
in steam sterilization, the greater the pressure applied, the _______ the temperature
greater pressure applied = higher temperature
in steam sterilization, name the 3 usual pressures applied, and their corresponding temperature and amount of time
115.5 degrees celsius for 30 minutes at 10psi
121.5 degrees C for 20 minutes at 15psi
126.5 degrees celsius for 15 minutes at 20psi
Steam sterilization is applicable to which pharmaceutical products?
those that can withstand the required temperatures and can be PENETRATED by the moisture but are NOT adversely affected
sealed containers such as ampuls are readily sterilized by this method.
sealed empty vials can only be sterilized through autoclaving if they contain a small quantity of water
differentiate between the steam sterilization capabilities of aqueous and oleaginous solutions
aqueous – the moisture is already present. just need to raise the temp for sterilization
oleaginous – cannot be done. no moisture present – may be damaged by the applied moisture
can steam sterilization be used on bulk solutions, glassware, and surgical dressings and instruments?
yes
steam sterilization can NOT be used on/…..
oils, fats, oleaginous preparations, and other preparations not penetrated by moisture
OR for exposed powders – may be damaged by the condensed moisture
dry heat sterilization uses what equipment to complete its task?
sterilizing ovens
how do microorganisms die in dry heat sterilization?
through oxidation
which is more effective in killing microorgansims – dry heat or moist heat?
moist heat
name the products that dry heat sterilization is good for
dry glassware, petroleum jelly, mineral oils, talcum powder, and some dry powders
explain the temperature and time period for dry heat sterilization
150 - 170 degrees celsius for at least 2 hours
which is the method of choice for when dry apparatus and containers are required, as in the handling of packages of dry chemicals and nonaqueous solutions —- steam sterilization or dry heat sterilization?
dry heat
which has higher temps and longer periods of exposure and WHY:
steam sterilization or dry heat sterilization
dry heat — less effective in killing microorganisms so needs higher temp and longer duration
what is a major disadvantage of dry heat sterilization
not all drugs remain stable at such a high temperature
sterilization by filtration is used for what?
solutions that can’t be heated
sterilization by filtration is accomplished how?
by using one of the several bacterial filters.
they work by interlacing pores and bacteria/particles become trapped in these pores and are removed
name 5 advantages of sterilization by filtration
-speed in filtering small quantities of solution
-ability to sterilize thermolabile materials
-inexpensive
-development and proliferation of membrane filter technology
–complete removal of both living and dead microorganisms and other particulate matter from solution
_____micron (micrometer) filters reduce the in vitro antimicrobial activity of…….
while filtration through ____ did not
0.22 micron, amphotericin B (a colloidial susoension)
while filtration of amphotericin B through 0.85 and 0.45 micron filters did not
give a specific example of a filter unit
MILLEX
Explain how gas sterilization works
destroys all living microorganisms with a chemical in the GASEOUS or VAPOR state
some chemicals used” ethylene oxide, propylene oxide
some ____ sensitive and ___ sensitive materials can be sterilized much better through gas sterilization
heat sensitive and moisture sensitive – big advanateg
besides the fact that it can sterilize heat and moisture sensitive materials, give another major advantage of gas sterilization
ethylene oxide gas has great PENETRATING abilities. thus, it is a useful agent to sterilize medical and surgical supplies such as catheters, plastic disposable syringes, etc
explain how sterilization by ionizing radiation works
uses either UV light or gamma radiation – still subject to investigation on how it actually works
name a disadvantage of sterilization by ionizing radiation
application of these techniques is limited because of the highly specialized equipment required and the effects of irradiation on the products and their containers
in the biological indicator for the validation/verification of sterility, what does A represent and what does B represent?
A = initial microbial population
B = number of microorganisms that survive after a defined heating time
what do pyrogens cause?
febrile reactions
what are endotoxins?
a subset of pyrogens that come from gram NEGATIVE bacteria
differentiate between endotoxins and lipopolysaccharide
endotoxins are the NATURAL complex of LPS whereas LPS is the purified form, used as a standard for quality control and research purposes
do gram positive bacteria have endotoxins, exotoxins, or both
just exotoxins
name 2 ways in which pyrogens are destroyed
-heating at high temp (250 degrees celsius for 4 hours)
-a potassium permanganate/barium hydroxide filter (oxidize them – they’re organic)
explain and name the USP pyrogen test
called the USP rabbit test.
uses healthy rabbits that have been properly maintained, and whose base temperatures differ no more than 1 degree celsius
heat the syringes, needles, and glassware at 250 degrees celsius for at least 30 mins to make them “pyrogen free”
warm the product to be tested as well
inject into each rabbit and record temps ever 30 mins hours 1-3
if no rabbit shows rise in temp above 0.5 degrees celsius, product meets pyrogen requirements
explain the endotoxin test
uses the blood cells of a horseshoe crab. (limulus polyphemus)
contains an enzyme that clots in the low presence of LPS
preparing the formulation of a parenteral product includes selecting what?
proper solvents/vehicles and additives
when preparing parenteral products, what important factors should be practiced
must be sterile and pyrogen free
why are some injections packaged as dry solids rather than in conjunction with a solvent?
how should these dry solids be sterilized?
because the therapeutic agent is unstable in the presence of the liquid component
should be sterilized through DRY HEAT or another appropriate method
explain the packaging of Mix-O-Vial
has dry ingredients in the bottom compartment and a liquid diluent at the top, separated by a seal.
explain how ADD-vantage works
2 components – flexible plastic container with diluent, and a glass vial with the medication and “piggybacks”
drug is release by removing the stopper between the 2 , allowing them to mix.
this preserves the closed, sterile system
name the 2 types of dosing containers for parenteral solutions
single-dose containers
multi-dose containers
name 3 types of packaging for parenteral solutions
ampuls
vials
pre-filled syringes
what is the oldest type of parenteral product container? what is it made of?
ampuls – made entirely of glass
are ampuls intended for single or multi dose use? how are they opened?
single use ONLY
opened by breaking the glass at a line on the neck
how are ampuls sealed?
by the fusion of the glass container under aseptic condition
for which dosing container does the product have to be FILTERED before administration? why?
ampuls
this is because in order to open it you have to break the glass at a line on the neck, so glass particles may be in there
give the definition of a parenteral vial
a glass/plastic container that is closed with a rubber stopper and sealed with an aluminum crimp
name 3 advantages of VIALS over ampuls
-is a multi-dose container with a bacteriostatic agent
-easier to remove the product
-this easy open eliminates the risk of glass particle contamination during opening
name 2 disadvantages of vials
-multiple withdrawals can result in microbial contamination
-rubber stopper can become “cored” by the needle
classify the glass containers used for parenteral vials
Type I - borosilicate
Type II - soda-lime treated glass
Type III - soda lime glass
explain Type I glass container
made of borosilicate
it is chemical resistant and has low thermal coefficient of expansion (doesnt expand a lot when exposed to heat)
Explain Type II glass container
soda-lime treated glass
has a lower concentration of migratory oxides than type III
is treated with sulfur ocide to dealkalize the internal surface (make more acidic)
used for solutions with pH less than 7
explain what Type III glass containers are good for
soda-lime glass
good for anhydrous (no water) liquids or for dry substances
name 2 types of plastic polymers that are potentially used for plastic containers
differentiate them
PVC (polyvinylchloride) and polyolefin
PVC = flexible and non rigid
polyolefin = semi-rigid, but can be stored upright
name 4 advantages of plastic containers over glass
unbreakable
easier to store
weighs less
improved safety
pre-filled syringes and cartridges are designed for _____ and are administered when?
designed for maximum convenience and administered in an EMERGENCY
Give 2 examples of drugs that are pre-filled and available for immediate injection
atropine and epinephrine
explain how pre-filled syringes/cartridges have improved accuracy
the medication is premixed and premeasured. has the needle already attached to the prefilled medication cartridge
____ are ready-to-use parenteral packages
tubex
tubex consists of a ___or ___ cartridge holder
metal or plastci
infusion solutions are used for….
the intermittent or continuous infusion of fluids or drugs
differentiate between small volume parenterals (SVP) and large volume parenterals (LVP)
small volume = less than 100mL
large volume = 100 mL or greater
true or false
parenteral products are overfilled somewhat
true
which are overfilled more – mobile liquids or viscous liquids?
viscous
Laminar flow hoods have what kind of filters?
HEPA filters
(high-efficiency particulate air filters)
what does federal class 100 mean
related to air quality (in this case in laminar flow hood)
no more than 100 particles sized 0.5 micrometers or larger per cubic foot of air
name the 2 types of laminar flow hoods
vertical and horizontal
explain the purpose of vertical laminar flow hoods vs horizontal
vertical – prevents the materials from being blown at you. like toxic things and chemoreactants
horizontal – air flows to you
name the 7 requirements for the labeling of injections
-name of the preparation
-for a LIQUID, % content of the drug or the amount of drug in a specified volume
-for DRY preparation, the amount of active ingredient present and the volume of liquid to be added to prepare the solution/suspension
-the ROUTE of administration
-statement of STORAGE CONDITIONS and EXPIRY DATE
-name of manufacturer and distributor
-identifying lot number that can yield complete manufacturing history of the specific package, including all manufacturing, sterilizing, and labeling operations
when is the expiry date of a drug?
when the API is at less than 90% potency
