Part 1 Flashcards
true or false
preformulation studies are ONLY related to the API itself
true
the dosage form includes….
the API and all excipients
true or false
drug substances are often administered alone
FALSE
they are administered as part of a formulation, in combination with one or more nonmedical agents (excipients) that serve varied and specialized pharmaceutical functions
drug substances are SELDOM administered alone
name 9 functions of pharmaceutical ingredients
solubilize
suspend
stabilize
thicken
dilute
emulsify
preserve
color
flavor
in a nutshell, what is the function of pharmaceutical ingredients?
to fashion medicinal agents into efficacious and appealing dosage forms
each type of ______ is unique in its ____ and _____ characteristics
each type of DOSAGE FORM is unique in its PHYSICAL and PHARMACEUTICAL characteristics
give an example of when we would want to thicken a dosage form
in the case of eye drops, we can thicken them to increase the retention time. this minimizes loss of the medication and it needs to be applied less frequently
do elixirs need a preservative?
NO
elixirs have enough alcohol to not need a preservative
give an example of when a preservative would be needed
with a lot of free water
do large volume IVs need preservative?
NO they are single dose. don’t need preservative
give an example of when a diluent excipient would be needed
for the tablet dosage form
especially needed if the drug is a very low dose, as a tiny drug would be impossible to properly handle
of the 9 functions of pharamaceutical ingredients (excipients), which function is the most important and the biggest concern
STABILIZE
for example, vitamin C is highly susceptible to oxidation and needs to be stabilized
as mentioned, each type of dosage form is unique in its physical and pharmaceutical characteristics
the excipients used is contingent on what?
the duration, onset time, etc
the ultimate goal is to obtain the maximum treatment with minimum side effects
what is the main concern in the case of stability?
the environment–
-oxidation
-hydrolysis (humidity)
-photolysis (light)
also microorganisms
true or false
stability is a concern with both the API itself as well as the entire formulation
true
what are methods to protect the drug substance from the destructive influences of atmospheric oxygen or humidity?
coated tablets and sealed ampuls
oxygen can’t penetrate these things and no microorganisms can come into sealed ampuls
for which dosage form is gastric acid destruction the biggest concern? what is done to combat it?
oral dosage form. gastric acid is an extremely low pH and the API will degrade in this environment. it needs to be protected
enteric coated tablets are produced. these will not dissolve in the stomach (will dissolve at high pH) and cause irritation. the tablet will dissolve in the small intestine instead.
ex: aspirin is weakly acidic and would normally dissolve in the stomach, but enteric coating prevents this
what is done to conceal the bitter or bad taste or odor of a drug substance?
the use of capsules, coated tablets, and flavored syrups
explain how capsules are utilized to mask the bad taste of a drug.
wouldn’t capsules still dissolve on the tongue and leave a bad taste?
capsules are formulated such that they will not dissolve in the mouth – the shell will not dissolve in cold fluids but only the warmth of our body fluids
as long as _________the bitter taste of a drug will not be noticed
the drug doesnt release on the tongue
liquid preparations of drugs substances can be prepared as ___ or ___
dispersions (suspensions)
clear preparations (solutions)
true or false
the solid dosage form is normally preferred, but the liquid dosage form is required for some populations
true
which uses a cosolvent system – solutions or suspensions?
solutions. cosolvent system is used to ensure that the drug will dissolve
how can rate-controlled drug action be provided?
through various controlled release tablets, capsules, and suspension
true or false
the higher the drug concentration, the higher the solubility
FALSE – the higher the dissolution rate
are suspensions an example of a rate-controlled drug?
yes
the solid powder is in the stomach and is slowly dissolving. this controls the dissolution rate – slowly. will have low concentration available overall, degradation is less and bioavailability is INCREASED as compared to solution.
extended duration of therapy.
in the case of solutions, it will be subject to quick degradation because all of the drug is already in solution and available for degradation
true or false
it is easier to optimize drug action of topical drugs as compared to oral drugs
true
explain how the insertion of a drug into body orifices is available
through the rectal and vaginal dosage forms
what dosage form(s) allow doe the placement of drugs directly into the bloodstream or body tissues?
injections
name topical dosage forms (6)
topical dosage forms allow for…
ointment
cream
transdermal patches
ophthalmic
ear
nasal
topical dosage forms allow for OPTIMAL DRUG ACTION
One of the needs for dosage forms is to provide for optimal drug action through……
both topical administration sites and inhalation therapy (inhalants and inhalation aerosols)
how do you increase the retention time at the site of the stomach for a solution dosage form whose site of action is the stomach?
through a viscosity agent to thicken – will increase the time at the site of action of the stomach
will go from stomach to small intestine very quickly if too thin.
solutions include……
- API
- Solvent(s)
true or false
most APIs are solid powders
true
for a tablet to have an effect what has to happen?
it needs to dissolve
what determines if a drug will dissolve?
solute-solute
solute-solvent
solvent-solvent interactions.
through various forces and bonds—
-van der waals
-ion-dipole
-ion-induced dipole
-hydrogen
-ion-ion
WHAT 3 THINGS NEED TO BE CONSIDERED IN PREFORMULATION STUDIES?
- physiochemical properties of the drug itself (API – no excipients yet)
- Biopharmaceutical considerations (ADME)
3, Therapeutic consderations of the disease state
as mentioned, one of the 3 main things to be considered in preformulation are the physiochemical properties of the drug itself.
explain this further
-the forces and bonds
-the states of matter
-stable solid dilutions
-UNSTABLE solid dilutions
-liquid-aqueous concentrates (mixing elixir w solution)
-acids and bases
-liquid-oil concentrates of liquids (ie: emulsion)
-drug and product stability
give an example of a stable, solid dilution
AND an unstable, solid dilution
in most cases, 1mg of API combined with 99mg of excipients will be stable
unstable – nitroglycerin. nitroglycerin easily evaporates, so it is not opened in the pharmacy and the patient will receive the full bottle
give an example of a liquid-aqueous concentrate.
is it any concern?
mixing elixir with solution.
this could be an issue because a solution has little to no alcohol content. this can pose a solubility issue
explain how biopharmaceutical considerations are something to think about for preformulation
ADME
D – after the drug dissolves, how will it get from plasma to the receptor site? if it doesnt get there, there is no therapeutic effect
M – 1st pass effects of liver. Most of the drug is destroyed in the liver and only a small amount survives to get into circulation
true or false
when all is said and done, all dosage forms will end up as a solution
true – they have to dissolve in order to have therapeutic effect
true or false
the drug only has to reach the receptor site in order to exert therapeutic effect
FALSE – needs to actually bind to the receptor
true or false
if the body considers a drug to be “safe”, it does not undergo metabolism and 1st pass effects
true
what is step 1 of drug design after the drug has been discovered
preformulation studies
what is the #1 concern of a solid dosage form
solubility.
drug MUST dissolve in order to exert effect
under preformulation studies, what “physical description” must be studied?
the appearance, color, odor, and taste
why is microscopic examination part of preformulation studies?
the particle size and range of the raw drug substance must be determined, as well as the crystal structure
this is related to SOLUBILITY which is the #1 concern of the solid dosage form
why is heat of vaporization part of preformulation studies
mainly in determining the vapor pressure for implantable pumps and aerosol dosage forms
why is melting point depression part of preformulation studies
if i add “x” excipient, how much will the melting point decrease?
for instance, salt lowers the melting point of water to melt snow
the higher the molecular weight, the ____ the melting point
higher
why is the “phase rule” part of preformulation studies
if we have 2 phases in a formulation, we want to know the interaction between them
if we add a surfactant to this, there are now 3 phases – we want to know the interaction between the 3 phases
true or false
if the particle size is decreased, there is a substantial increase in solubility
FALSE
the intrinsic solubility does not change, but the dissolution rate increases due to higher surface area which makes it faster to prepare
HOWEVER, it is also possible for the particle size to be so small that it can’t interact with the solvent and dissolve
what is the freezing point of water
the freezing point of PURE water is 32 degrees F
HOWEVER, impurities can affect the melting/freezing point
upon the addition of a second component, which melting point is MORE LOWERED—
-a compound with a low melting point
-a compound with a high melting point
the low-melting point compound will be affected to a greater extent (greater lowering of melting point)
are pka/dissociation constants part of preformulation studies?
yes
expresses the extent of ionization
how are organic salts obtained?
from acid base reactions
name 5 things that particle size has an effect on
(IMPORTANT)
-drug dissociation rate
-bioavailability
-content uniformity
-flow characteristics
-sedimentation rates
one of the parameters that particle size has an effect on is bioavailability.
explain what this is
the amount of drug available in systemic circulation and is thus able to have an effect
explain how particle size affects content uniformity
if small and large particles are mixed together (not uniform), the large particles will sink and the dose will not be right
explain how particle size affects flow characteristics
capsule/tablet dosage form is preferred.
when manufacturing in the industry, the powder to make the tablet/capsule needs to flow evenly so that all the dosage forms are even and uniform
what are the methods of evaluating particle size?
- Sieving or screening
- Microscopy
- Sedimentation
- Stream scanning (coulter counter, hiac counter)
when the particle size of water insoluble drugs is reduced, ____ increases, this results in higher _____
DISSOLUTION RATE increases and this results in higher AVAILABILITY AT THE ABSOPRTION SITE (bioavailability)
what is sieving
like sifting in baking.
method to evaluate particle size
what is microscopy
method of evaluating particle size AND crystal structure
what is stream scanning
includes coulter counter and hiac counter.
method to evaluate particle size and the number of particles.
a shadow is created to find out this information
true or false
the particle size of the API is the only concern
FALSE – both API and excipients.
want a similar size between them
particle size is most especially important in ____ dosage form
parenteral
if reducing the particle size doesn’t work to dissolve, what can be done next?
polymorphism
true or false
if a drug is water soluble, bioavailability isn’t really a concern
TRUE
water soluble molecules don’t undergo first pass effects and are able to dissolve in the blood
____-____% of drugs in the market use polymorphic API
does this need a new NDA?
15-20%
YES
when going from crystalline to amorphous form, the drug is considered new and an NDA is needed
many new drugs are water insoluble.
this can be combatted by reducing the amount of API in the formulation.
does this need a NDA? what is the concern with this?
does NOT need an NDA
this is a concern bc reducing the amount of API can affect the bioavailability. we need a sufficient bioavailability to have therapeutic effect
which has a higher dissolution rate – amorphous or crystal form?
amourphous
when a drug precipitates, energy is ______ and it is now _____
when a drug precipitates, energy is RELEASED and it is now STABLE
LOW SOLUBILITY requires energy to reintroduce to liquid state
is more energy required to go from liquid to solid or solid to liquid?
solid to liquid
when a polymorphic drug is compared to a crystalline drug, which requires more energy from outside to transform the compound from solid to liquid?
crystalline requires MORE ENERGY to change
do polymorphic drugs contain energy?
yes, they retain some energy
which has a lower melting point – polymorphic or crystalline form?
polymorphic
true or false
different polymorphs of the same drugs have the same physiochemical properties
FALSE
this is why the FDA considers it a new drug and requires a new NDA
different polymorphs can have different ____,_____, and ____
density vapor pressure and stability
how are polymorphs prepared?
the drug is rapidly precipitated from the solvent which does not allow the drug molecules enough time to form an orderly array.
the drug is rapidly cooled and spray dryed/freeze dried
the goal is to retain ENERGY in the structure BUT we also want it to have a decent stability and dissolution
