Chapter 1 - Basic Concepts Flashcards
if there is 100mg of drug administered and 80mg in circulation, what is the bioavailability
0.8
symbol for bioavailability
f
3 examples of how an API/drug can be simply chemically modified
forming esters
forming salts
forming complexes
true or false
it is not possible for different dosage forms of the same drug to have different bioavailability in systemic circulation
FALSE - it is very possible
ie - bioavailability of IV is always 100%. oral is usually much lower
briefly explain what biopharmaceutics is
the study of the relationship between the intensity of biological effects observed in living things and the characteristics of the drug and dosage form (ie - how does adjuvant affect bioavailbility and the subsequent clinical result?)
true or false
intravenous injections have a rapid absorption mechanism
FALSE - NO ABSORPTION AT ALL
always 100% bioavailable. goes directly into circulation
define absorption
process of the drug going from the GI tract (or other site - like through the skin) and into the blood
the “plasma profile” we aim to control describes the amount of drug located where?
in CIRCULATION
true or false
for every route of administration besides IV, absorption occurs
TRUE
even if it’s only a little bit - still absorbed somehwat
true or false
IV infusion is an example of zero order kinetics
true
can drug go from the circulation and into the GI tract?
YES, but very small amount
what is the term for drug going from the circulation and into the tissues
distribution
fick’s law
as concentration decreases, the rate decreases as well
true or false
if 2 manufacturers make the same product (same drug, same dosage form), it is not possible for them to have different plasma concentrations
what if it’s the SAME manufacturer, same dosage form, same drug?
FALSE - it is - bc of different manufacturing processes
could STILL BE DIFFERENT - even if the manufacturer is the same
2 general factors influencing drug availability
-physiochemical properties of the drug substance (API itself)
-Formulation factors that affect the drug releasing from the DOSAGE FORM
as drug concentration gets lower at the absorption site, where is it going
into the body
as drug concentration decreases in the body (systemic circulation), where is it going
either metabolized in the liver or getting excreted by the kidneys
what helps us determine if the dose of a drug should be increased or decreased
the plasma profile
prior to being absorbed, what must happen to the drug
MUST dissolve in the fluid at the absorption site - must be water soluble!
true or false
reducing the particle size of a drug always increases its bioavailability
FALSE - doesn’t always work and may have to play around with other things
for which does reducing particle size have a greater effect on increasing the bioavailability:
-drug that is poorly water soluble
-drug that is water soluble
drug that is poorly water soluble - can be expected to have greater effect on increased bioavailability
explain why reducing the particle size can help to improve bioavailability
reducing the particle size INCREASES THE SURFACE AREA, thus increasing the dissolution RATE (NOT the solubility of the drug itself)
true or false
reducing the particle size of a drug increases it solubility in water
FALSE - does not increase solubility. increases DISSOLUTION RATE
solubility is a constant value for each drug
true or false
reducing the particle size increases the surface area
true
true or false
let’s say a drug is being administered as 500mg capsule
it is found that the micronized form has a higher dissolution rate
is it possible to reduce this 500mg to a lower value and still get the same effect? (if we use the micronized version)
YES
true or false
small particle size can actually be bad for some drugs
TRUE
for drugs that already dissolve quickly, this could be bad bc the drug will be there in very large quantities
OR reducing the particle size for drugs unstable in gastric fluid may enhance their inactivation
true or false
small particle dissolve at a faster rate than larger particles
true
for a drug unstable in gastric fluids, what particle size do you want
COARSE - not super tiny. a super tiny particle size will make it all get degraded very quickly
rate of inactivation is slower with a coarser particle size
a high particle size can slow down the gastric inactivation of some drugs
what else may be beneficial about a large particle size
may reduce side effects
true or false
polymorphism is very uncommon for drugs
false - common - around 70% of drugs
true or false
compared to the crystalline form of a drug, the polymorphic form contains less energy
FALSE - contains more internal energy, so LESS external energy is needed for it to dissolve
true or false
polymorphic forms are less stable than crystalline forms
true
true or false
polymorphic forms have greater solubility than crystalline forms
true
true or false
crystalline forms have a faster dissolution rate than polymorphic forms
FALSE - slower dissolution rate
true or false
weak organic bases/acids are very water soluble
FALSE - poorly water soluble and need to be turned into their salt form
what is the term for the dissociation constant of acidic/basic drugs
acidic - Ka
basic - Kb
explain how the dissociation constant of drugs is useful in determining its absorption
drugs in unionized forms are easily absorbed, but NOT easily soluble in the GI fluid
dissociation constant indicates the extent to which a drug will dissociate into its IONIZED FORM
if lot is ionized - won’t be well absorbed through GI membrane but will dissolve
formula for partition coefficient
concentration in oil/conc in water
the rate of permeation of a drug through the membrane is based on what
FICK’S FIRST LAW
explain what Fick’s first law is
the rate of diffusion of a substance through the membrane is DIRECTLY PROPORTIONAL to the concentration gradient
the drug diffusing through the membrane must be in ____ form
solution (dissolved)
true or false
according to Fick’s first law, the lower the concentration gradient, the higher the rate of diffusion
FALSE - the higher the concentration gradient, the higher (faster) the rate of diffusion
*class I solubility and permeability
high solubility, high permeability
*class II solubility and permeability
low solubility, high permeability
*class III solubility and permeability
high solubility, low permeability
*class IV solubility and permeability
low solubility, low permeability
a drug is considered highly soluble when…..
the HIGHEST DOSE STRENGTH is soluble in 250mL or less of aqueous media over pH range 1-8
as mentioned, a drug is considered highly soluble when the highest dose strength is able to dissolve in 250mL or less in the aqueous media, over a pH range 1-8
when is a drug considered to have LOW SOLUBILITY
if the volume of aqueous media needed to dissolve the drug over pH 1-8 is OVER 250mL
when is a drug considered to be highly permeable
when the extent of absorption is over 90% of the administered dose
how to improve the bioavailability of a class II drug
class II has low solubility and high permeability.
to improve solubility profile, reduce the particle size to increase the dissolution rate! bioavailbility will increase
true or false
class III has lower solubility than class II
FALSE - class II has lower solubility
class III solubility is high
can tetracycline be dissolved in ringer injection solution
NO - contains calcim, will form a complex
do excipients affect the bioavailability of the drug
YES
Na CMC + amphetamine
decreased bioavailbility of amphetamine bc of interaction
what does phenobarbital react with and what is the result
PEG 4000.
absorption of phenobarbital is reduced
component of some dosage forms that is hydrophobic
magnesium stearate (lubricant) in tabs and caps
3 tablet characteristics that influence bioavailability
-tablet hardness
-tablet disintigration
-coating (enteric, film)
what is the modified Noyed-Whitney equation based on
DISSOLUTION RATE
controls the amount of drug in solution
name an oral dosage form that is immediately available in solution to be absorbed
solutions
true or false
emulsions have the same absorption rate as solutions
FALSE
emulsions depend on the drug partitioning between the aqueous and oil phases of the emulsion
the time for a tablet to DISINTEGRATE depends on what
on the compression used
higher compressional force used = harder tablet – disintegrate SLOWLY
rate limiting step for drug absorption from tablets for drugs that are:
-poorly water soluble
-poorly lipid soluble
poorly water soluble - dissolution rate is the rate limiting step
for poorly lipid soluble - rate at which drug crosses cell membrane
the application of kinetics is the study of….
KADME
“Kinetics of ADME”
what is Cp
plasma profile
2 different types of plasma profile
IV plasma profile (zero order)
oral plasma profile (typically 1st order)
true or false
pharmacokinetics can help to predict the concentration of the drug in various tissues and fluids of the body
true
the steady state plasma concentration of a drug is more relevant for which type of drug?
steady state concentration is more relevant for a drug that is administered chronically rather than for a short period of time
as mentioned, the steady state plasma concentration is more relevant for a chronic drug than one that is only administered for a short amount of time.
what about half life?
half life is important for ALL drugs
AUC is a measure of…
the extent of drug absorption into the systemic circulation
(extent that was absorbed from the administered dose)
