Part 2 Flashcards
besides reducing particle size and polymorphism, name 5 more ways in which solubility can be improved
-salt/ester formation
-pH
-cosolvent system (solutions)
-surfactants
-complexation
explain how salt/ester formation can improve solubility (give a specific example)
phenobarbital is a weak acid and is not very water soluble.
when it reacts with a base, the salt is formed which is very hydrophilic and thus water soluble
explain how pH can improve solubility
changing pH changes the ratio of ionized: unionized (Hendersen Hasselbalch eqn)
this is not really done a lot because the pH of the body can’t be changed
explain how cosolvent systems can improve solubility
can improve the solubility of poorly soluble drugs by using cosolvents such as–
-propylene glycol
-glycerin
-sorbitol
-polyethylene glycol
can the cosolvent system be used for the solid dosage form?
NO
explain how surfactants can improve solubility
ONLY for liquid and semisolid dosage forms (NOT SOLID)
through the formation of micelles
give a specific example of a natural surfactant
bile salts increase our absorption of lipids
give a specific example of complexation
what is the function
cyclodextrins can form complexes with drug molecules to improve solubility
true or false
a drug does not necessarily need to cross a biological membrane to have a pharmacological response
FALSE
the drug needs to cross
explain the properties of the biological membrane
has protein and lipid material.
serves as a lipophilic barrier to most drugs
what is alpha (a) value represent
the extent/degree of ionization
give the 2 formulas for partition coefficient
P = (conc of drug in octanol)/(conc of drug in water)
P=(conc of drug in octanol)/(1-a)(conc of drug in water)
a=extent/degree of ionization. usually very small
the ratio of ionized:unionized molecules depends on…
the pH and pka (according to the Hendersen Hasselbalch equation)
the salt form of a drug _______ the ionized concentration and therefore ______ permeate and the partition coefficient is _____
the salt form INCREASES the ionized concentration and therefore CANNOT permeate and the partition coefficient is LOW
why is octanol part of the formula for the partition coefficient
it is an organic solvent that represents the biological membrane
hexanol can be used too
what is the ideal partition coefficient between:
P>1
P=1
P<1
explain
P=1 is the most ideal
if P is greater than 1, there will be good permeability but the concentration at the absorption site will be very low
however, if P=1, this means that if there are 200 molecules, 100 will permeate and 100 will not. this is ideal to maintain the balance between dissolution and permeation
if P is low, this means the drug is ____ soluble
water
if P is small, the concentration at the absorption site will be______
high, but it will not permeate
in regards to drug stability, are we concerned with the API or the entire product?
the entire product (obviously including the API)
name 8 stability issues
-hydrolysis
-oxidation
-drug substance-excipient interaction
-photolysis
-polymerization
-isomerization
-deamination
-decarboylation
give the definition of an acidifying agent and give examples
acidifying agent is used in liquid preparations to provide an acidic medium for PRODUCT STABILITY
examples:
acetic acid
citric acid
fumaric acid
hydrochloric acid
nitric acid
they basically adjust the pH of the solution
what is the main concern in LIQUID dosage form?
STABILITY
what is the main concern in the SOLID dosage form?
SOLUBILITY
Define an alkalinizing agent
used in liquid preparations to provide an alkaline medium for product stability
true or false
acidifying agents and alkalinizing agents are used in both liquid and solid preparations
FALSE – only liquid
give 10 examples of alkalinizing agents
ammonia solution
ammonium carbonate
diethanolamine
monoethanolamine
potassium hydroxide
sodium borate
sodium carbonate
sodium hydroxide
triethanolamine
trolamine
give the definition of an adsorbent and give 2 examples
an adsorbent is an agent capable of holding other molecules onto its surface by physical or chemical means
powdered cellulose
activated charcoal
true or false
activated charcoal is an adsorbent. it does not permeate and does not go into circulation
true
define an aerosol propellant
an agent responsible for developing the pressure within an aerosol container and expelling the product when the valve is open
what is a coolant?
a liquid that absorbs heat quickly
what is an air displacement agent? give example(s)
an agent that displaces air in a hermetically sealed (airtight) container to enhance product stability
nitrogen
carbon dioxide. they’re sealed into the container to displace air and prevent oxidation
name the different dosage forms available for tagamet
solution
tablet
large volume IV
small volume IV
solution
viscous liquid
air diaplacement is related to maintaining the ___ of the product
stability
if liquid/semi-solid dosage form contains sugar and free water….
antifungal preservative is required
give the definition of an antifungal preservative
used in LIQUID and SEMISOLID preparations to prevent the growth of fungi
effectiveness of the parabens is usually enhanced if used in combination
name 7 examples of antifungal preservatives
methylparaben
ethylparaben
propylparaben
butylparaben
benzoic acid
sodium benzoate
sodium propionate
between sodium benzoate and benzoic acid, which would you select to have HIGH ACTIVITY
low activity but long duration = sodium benzoate
benzoic acid = high activity but low duration
thus, benzoic acid would be the choice
define an antimicrobial preservative
used in liquid and semisolid preparations to PREVENT THE GROWTH OF MICROORGANISMS
true or false
antimicrobial preservative and antifungal preservative are interchangeable terms
FALSE
antifungal prevents the growth of fungi and antimicrobial prevents the growth of microorganisms.
they are NOT the same
are preservatives used in single dose containers?
NO
name 9 antimicrobial preservatives
benzalkonium chloride
benzethomium chloride
benzyl alcohol
cetylpyridinium chloride
chlorobutanol
phenol
phenylethyl alcohol
phenylmercuric nitrate
thimerosol
of the 9 antimicrobial preservatives mentioned, which is very corrosive to the skin?
phenol. also used in lysol
of the 9 antimicrobial preservatives listed, which is popular in eye solutions as a preservative?
thimerosol
true or false
benzalkonium chloride and benzethonium chloride are both antimicrobial preservatives and surfactants
true
no more than _______ mL of preservatives can be injected via IV
no more than 5mL
true or false
infusions are multi dose and do not need antimicrobial preservatices
FALSE
they are single dose and therefore don’t need preservatives
true or false
if there is no preservative, the liquid/semisolid dosage forms cannot be used more than once
true
true or false
according to the USP, at times a small amount of microorganisms is okay
true, but if the limit is exceeded it poses a stability issue
antioxidants are used to ensure _____
stability
define an antioxidant
an agent which inhibits oxidation and is thus used to prevent the deterioration of preparations through oxidation
how to antioxidants accomplish their function?
they undergo a reaction with oxygen and “sacrifice themselves” in the process. they have very high activity
true or false
antioxidants aren’t bad for our body
false. too much antioxidants can cause cancer
name 4 examples of antioxidants
ascorbic acid
BHA (butylated hydroxyanisole)
BHT (butylated hydroxytoluene)
Sodium ascorbate
what is the composition of vitamin C supplement
ascorbic acid and sodium ascorbate and sugar
ascorbic acid is very bitter. sodium ascorbate and sugar are added to reduce the bitter taste
which antioxidants are used in food?
BHT and BHA
why are buffering agents used?
to resist changes in pH upon dilution or addition of acid or alkali (base)
inhibit pH change
explain the components of a buffering agent
contains a weak acid and its salt (weak base) or a weak base and its salt (weak acid)
reversible reaction to maintain equivalence
give an example of a buffering agent
monobasic sodium acetate
define a chelating agent
a substance that forms stable, water soluble complexes (chelates) with metals
what is a chelate
a stable, water soluble complex with a central metal atom
when is a chelating agent used in pharmaceuticals?
used in some liquid preparations as STABILIZERS to complex heavy metals that might cause instability
(SEQUESTERING AGENT)
True or false
a chelating agent forms a complex with organic molecules
FALSE – with metals
give example(s) of a chelating agent
Edetate disodium (Na2 EDTA)
Edetic acid (EDTA)
both ____ and _____ are not allowed for infants, as it causes organ damage
both coloring and preservatives
define a colorant
used to impart color to liquid and solid pharmaceutical preparations
colorants are mainly used for which dosage form
tablet dosage form. tablet is the most popular
name 2 NATURAL colorants
caramel (used in coke)
ferric oxide
true or false
it is preferred to use natural colorants over artificial
true
there are ____ types of colorant:
2: natural and artificial
ferric oxide imparts what color?
orange-pink (natural colorant)
