Parenterals Part 2

Question 1

goal of sterility

Answer 1

complete DESTRUCTION (or removal) of ALL living organisms and their spores

Question 2

5 sterilization methods

Answer 2

steam
dry heat
filtration
gas
ionizing radiation

Question 3

3 different approaches to ensuring sterility

Answer 3

-initial control
-sterilization before use
-add preservatives

Question 4

*****name 4 things that CANNOT be sterilized via steam/moist heat and state why

Answer 4

oils
fats
oleaginous preparations
powders

they may be damaged by condensed moisture - moisture sensitive

Question 5

“D value” meaning*

Answer 5

time (in minutes) required to destroy 90% of microbes under set of conditions

Question 6

true or false

if a drug is sensitive to water, it can be sterilized via Dry Sterilization

Answer 6

true

ie - various petrolatum (oily) products AND glassware

Question 7

how are the microbes destroyed in steam sterilization? what about dry?

Answer 7

steam - denaturation and coagulation of the proteins of the microbes

dry - dehydration and slow burning or oxidation

Question 8

compare the TIME and the TEMPERATURE for moist (steam) vs dry heat sterilization

Answer 8

dry is at a higher temperature and for longer period of time (hours vs minutes)

Question 9

true or false

if a drug is sensitive to heat, the filtration method of sterilization can be used

Answer 9

true

Question 10

**PORE SIZE for the microbes for filtration method of sterilization

Answer 10

0.22 micrometers (the microbes are larger than this and won’t pass)

Question 11

for which drugs is filtration NOT recommended

Answer 11

drugs with small doses (less than 5mg) – until their is enough data to show that there is no significant adsorption

Question 12

name some things that can be sterilized by GAS STERILIZATION

Answer 12

heat-sensitive and moisture-sensitive materials

medical devices (catheters, needles)

some heat-labile enzymes and antibiotics

Question 13

name 2 gasses that can be used for gas sterilization and the mechanism

Answer 13

ethylene oxide or propylene oxide

ethylene oxide is an alkylating agent that interferes with cell metabolism of the microbe

Question 14

*drug is water-sensitive but stable when heated

which sterilization method can be used?

-steam sterilization
-dry heat sterilization

Answer 14

dry

Question 15

*true or false

a 5 micron filter is NOT sufficient to remove microbes and sterilize

Answer 15

TRUE

must be 0.22 microns

5microns can be used to remove large particles, but NOT microbes

Question 16

concern with ionizing radiation

Answer 16

may accelerate drug and polymer degradation

Question 17

name some things that ionizing radiation sterilization can be used for

Answer 17

ointments
drug delivery inserts and implants
packaging materials

Question 18

drug that has incompatibility with benzyl alcohol

Answer 18

amphotericin B

Question 19

**looking at a product label and it says it contains “water for injection”

what is an important consideration?

Answer 19

MUST STERILIZE THE END PRODUCT!!!!!!!

Question 20

1 of the 4 S’s is “safety”

what does this mean

Answer 20

must be pyrogen free (pyrogens cause fever)

have clarity

be isotonic

Question 21

how is a parenteral product tested for safety (NO PYROGENS)

Answer 21

USP test is the rabbit febrile reaction

sample injected into the ear vein of a rabbit – and rectal temp is taken
0.6 degrees celsius over normal is FAILURE

another is the LAL test (limulus amebocyte lysate) – gel will form if pyrogens are there

Question 22

*USP chapter for bacterial endotoxin (pyrogen) testing standards?

*USP chapter for sterility testing?

Answer 22

pyrogen test - USP <85>

sterility test - USP <71>

Question 23

USP limit for particles in parenteral preparations (SAFETY)

Answer 23

50 particles of 10 micrometers or larger/mL (large volume infusions)

Question 24

what size filter to remove PARTICULATES in order to ensure safety (clarity)

Answer 24

5 micrometers

Question 25

**explain what happens between hypertonic and hypotonic solutions

Answer 25

if hypertonic, water will rush out of the RBC and the cell will shrink (because more salt is OUTSIDE)

if hypotonic, water will go into the cell and the cell will swell and burst (because LESS salt is outside)

Question 26

parenteral solutions being isotonic is important for which of the 4 S’s?

Answer 26

safety

because hypo and hypertonic solutions can cause cell damage and pressure – pain, irritation, inflammation

Question 27

what osmolarity is isotonic

Answer 27

280-310 mOsm/L

Question 28

when is an IV bag and active ingredient considered incompatible

Answer 28

if the loss of the potency of active ingredient is greater than 10%

Question 29

non polar and sparingly soluble drugs are generally not compatible with which type of containers and why

give a specific example

Answer 29

plastic containers – the drug tends to partition into the plastic container wall

nitroglycerin is a drug that has low water solubility. therefore, cant be put in a PVC (polyvinylchloride) IV bag! – PUT IN GLASS!!!!!!! with non-adsorbing infusion set. the dose of nitroglycerin is very critical

Question 30

sulfites are used as….

Answer 30

antioxidants

Question 31

what may sulfites be incompatible with

Answer 31

other drugs — they may react chemically and lead to inactive product and less therapeutic effect

Question 32

compatibility of cations

Answer 32

generally, monovalent cations are usually compatible

BUT

divalent cations (calcium and magnesium) can be problematic with certain things like bicarbonate citrate and phosphate – can form an insoluble complex

if bicarbonate - will release CO2 which is dangerous

Question 33

which particular drug has a WIDE range of incompatibilities and it is thus not advised to mix with any other drugs

Answer 33

amphotericin B

Question 34

precipitation can occur if amphotericin B is added to ____ or ____ solutions

Answer 34

sodium chloride 0.9% or to electrolyte solutions

Question 35

how is amphotericin B stored and infused

Answer 35

stored in amber bag bc sensitive to light

infused SLOWLY to avoid toxic effects and precipitation (pretty insoluble in water)

Question 36

what is the most common phthalate plasticizer used in flexibles bags, etc?

what is the concern with it?

Answer 36

DEHP (a plasticizer)

if given with a drug that dissolves a PVC bag, DEHP may leech out and it may get into the patient’s blood vessels

Question 37

alternatives to PVC/DEHP

Answer 37

Braun, Excel bags and PAB (PFV-free and DEHP free partial-additive bags)

Question 38

true or false

to minimize incompatibility issues, you should use freshly prepared solutions

Answer 38

true

Question 39

true or false

to minimize incompatibilities, preparations should always be shaken vigorously

Answer 39

false - only shake unless indicated in the labeling

Question 40

**sterilization technique for o/w emulsions

Answer 40

DRY STERILIZATION

cannot use heat bc oils and cannot filter oils either

Question 41

***API has to lose ____% potency to be considered incompatible

Answer 41

10%

Question 42

• do we want non aqueous vehicles to have a high or low boiling point

Answer 42

HIGH (over 170 degrees C)