Lab 8 Flashcards
The stability of a pharmaceutical product not only refers to the active ingredient(s) in the product, but also…….
the excipients, containers, and storage conditions
Give the USP definition of the stability of a pharmaceutical product
“the extent to which a product retains, within specified limits, and throughout its period of storage and use, (shelf life), the same properties and characteristics that it possessed at the time of its manufacture.”
name the 5 types of stability conditions maintained throughout the shelf life of a product
chemical
physical
microbiological
therapeutic
toxicological
explain what chemical stability is
each active ingredient maintains its chemical integrity and labeled potency, within specified limits
explain what physical stability is
the original physical properties (appearance, palatability, uniformity, dissolution, and suspendability) are retained
explain what microbiological stability is
the stability/resistance to microbial growth is retained according to the specified requirements.
the antimicrobial agents present retain effectiveness within specified limits
explain what therapeutic stability is
the therapeutic effect of the product remains unchanged
explain toxicological stability
no significant increase in toxicity occurs
true or false
all processes (like manufacturing, packaging, storage, distribution, and use) can affect degradation rate and product stability
TRUE
how is QUALITY achieved?
by evaluating and monitoring all processes (manufacturing, packaging, storage, distribution, and use)
after the manufacturing of a product, what happens?
the product is tested under several normal conditions as well as several stress conditions
name the FIVE most common types of degradation reactions
-hydrolysis
-oxidation
-photolysis
-dehydration
-racemization
the RATE of degradation can often be predicted by……….
-the number of reacting species OR
-the order of the reaction
INCOMPATIBILITY describes….
PREVENTABLE physical and chemical reactions that can be minimized or eliminated with the use of corrective measures
WHEN should the physical and chemical properties of a product be evaluated and resolved?
when designing the formulation
give an example of a PHYSICAL incompatability
the soluble, ionized form of a drug precipitates as a result of pH change during preparation or storage
give an example of a CHEMICAL incompatability and the solution for it
-heavy metals present in water can catalyze the oxidation of penicillin, epinephrine, and phenylephrine
-chelating agents (such as EDTA) are used to sequester these heavy metals to reduce this oxidation of the product
a(n)_____ in temperature accelerates oxidation, reduction, and hydrolysis reactions. this leads to drug degradation
INCREASE
the rate of a reaction doubles or triples for each ________ degree rise in temperature
the rate of a reaction doubles or triples for each 10 DEGREE CELSIUS rise in temperature
evaporation causes loss of __ And ____
water and volatile solvents
what does volatile mean
easily evaporated
WHY are volatile solvents commonly used on pharmaceutical products?
to assist in the solubilization of non-polar drugs, dyes, flavors, and aromatic oils
LOSS of volatile solvents results in…..
a supersaturated solution that readily precipitates/crystallizes.
loses its appeal due to changes in color and odor
_______ may increase the temperature of the product and increase the rate of evaporation and instability
temperature
_______ substances DEGRADE in the presence of light
photo labile substances
true or false
the intensity and wavelength of the light, as well as the size, shape, composition, and color of the container may affect the rate of the reaction of the degradation of photolabile substances
true
____________ has a high energy level and is more likely to cause photo instability or photo-oxidation
ULTRAVIOLET RADIATION
____ can bleach color dyes and reduce the appeal of a product
light
______ may catalyze the formation of free-radical intermediates that initiate chain reactions and increase the rate of degradation via oxidation
LIGHT
true or false
light decreases the rate of degradation via oxidation
FALSE – light increases it
___________ are used to reduce degradation via oxidation
antioxidants and chelating agents
what color glass gives considerable protection from ultraviolet radiation, but only a little protection from infrared radiation?
amber
what color glass gives the BEST protection from ultraviolet radiation?
yellow-green glass
give 5 examples of photolabile chemicals and drugs (sensitive to light)
-nitroprusside
-epinephrine
-vitamins
-riboflavin
-p-aminophenol
chemical degradation due to oxidation, hydrolysis, and reduction is related to the ___ content in the pharmaceutical product
WATER
the rate of hydrolysis is dependent on what 3 things?
-water content
-temperature of solution
-pH of solution
___ and ____ are MOST LIKELY to hydrolyze in the presence of water
esters and beta-lactams (penicillins)
_____ are less likely to hydrolyze as compared to esters
amides (acetaminophen)
drugs containing which 5 functional groups are prone to hydrolysis?
-esters
-amides
-imides
-imines
-lactam
explain hydrolysis in a zero order reaction
hydrolysis occurs IRRESPECTIVE of concentration
at a CONSTANT rate
for a zero order reaction, increasing the concentration will ____________ the %-age decomposition
SLOW
for first-order and higher reactions, the rate change is ______ proportional to the concentration of the active ingredient.
explain
DIRECTLY
increasing the concentration has no influence on the percentage decomposition
for a ___ order reaction, a greater portion of dilute solution is destroyed within a given time
zero
Hygroscopic products……
may absorb water and support microbial growth
(hygroscopic substances absorb water readily and liquefy to give a jelly-like appearance
the WATER CONTENT in a pharmaceutical preparation depends on what 2 things?
-the moisture content in the raw material
-use of water as a solvent
in HIGH HUMIDITY, what happens?
the water content of the preparation increases and preservative may not cover all of the free water – microbial growth is imminent
_____ and _____ are the most likely to cause a clinically significant loss of drug due to hydrolysis and oxidation reactions
pH and elevated temperature
true or false
it is not possible for a pH change of only 1 unit (4 to 3 or 8 to 9) to decrease drug stability by a factor of 10 or greater
FALSE – it is possible
Sometimes, _______ that is used to improve solubility may result in chemical degradation
pH adjustment
the _____ in aspirin is hydrolyzed to ____ and _____ in the presence of ______
the ACETYL ESTER in aspirin is hydrolyzed to ACETIC ACID and SALICYLIC ACID in the presence of MOISTURE
in a dry environment, the hydrolysis of aspirin is negligible
how can acetic acid and salicylic acid be detected?
salicylic acid can be detected with the use of ferric chloride and by using HPLC separation techniques
formation of acetic acid can change the odor of the product
weakly acidic and basic drugs show good solubility when ionized, but……
but they also tend to decompose faster
when the pH of the solution favors the UNIONIZED FORM, what happens when the concentration exceeds intrinsic solubility?
precipitation
sometimes, the use of pH adjustment to improve solubility may result in……
antimicrobial or sweetener ineffectiveness
Stability studies test what attributes of the API?
attributes that are susceptible to change during storage and are likely to influence the quality, safety, and/or efficacy
stability tests are conducted when the drug product is located where?
in its storage container and distribution packaging
the stability information obtained from stability tests is useful in assigning ____ and ____ dates
beyond use dates and expiration dates
acetaminophen is a ___ And ____ used in children and adults
analgesic and antipyretic (fever reduction)
in the lab, our acetaminophen products were kept in what conditions?
40 degrees celsius for 3 weeks
what is the hydrolytic product of acetaminophen? how was it detected in the lab?
p-aminophenol
detected using alkaline sodium nitroprusside solution
spectrophotometer used to detect color changes in the presence of p-aminophenol
the USP limit of p-aminophenol is _____% w/w of acetaminophen
0.005%w/w
the ___ reacts with ______ to give a bluish-green color
formed p-aminophenol reacts with alkaline sodium nitroprusside to give a bluish-green color
explain what the “SHELF LIFE” is
the time period in which the API or FPP (finished pharmaceutical product) is expected to remain within the approved shelf-life specification, PROVIDED THAT IT IS STORED UNDER CONDITIONS DEFINED ON THE CONTAINER LABEL
The API cannot be less than ____% of the labaled claim and not more than ____% degradation
API cannot be less than 95% of the labeled claim and not more than 1% degradation
what is a freezer as defined by USP
a place where temperature is maintained thermostatically between -25 degrees celsius and -10 degrees celsisu
what is “cold” as defined by USP
any temp not exceeding 8 degrees
REFRIGERATOR is a cold place (between 2 and 8 degrees celsius)
what is a “controlled cold temperature” as defined by USP
temperature maintained thermostatically between 2 and 8 degrees celsius
“cool” is defined as……
any tmperature between 8 and 15 degrees celsius
what is “the temperature prevailing in a working area”
room temperature
what is “controlled room temperature”
temperature maintained thermostatically between 20 - 25 degrees celsius
what is “warm”
any temp between 30 - 40 degrees celsius
what is “excessive heat”
any heat above 40 degrees celsius
what is the USP standards for a label stating “protect from freezing”
-risk of breaking container
-freezing subjects the product to loss of strength, potency, or to the destrutive alteration of its characteristics
what is a “dry place” according to the USP definition
a place that does not exceed 40% average relative humidity (RH) at controlled room temp, OR the equivalent water vapor pressure at other temperatures
