Chapter 9 - Solid Oral Modified Release Dosage Forms and Drug Delivery Systems Flashcards
true or false
all drugs are suitable for controlled release
false
how many modified release dosage forms are there?
name them
7
SR - sustained release
SA - sustained action
PA - prolonged action
CR - controlled release
ER - extended release
TR - timed release
LA - long acting
SR
sustained release
PA
prolonged acting
CR
controllled release
LA
long acting
TR
timed release
SA
sustained action
true or false
a disadvantage of modified release dosage forms is that they are more likely to cause more adverse side effects
false - there is actually a reduction in adverse side effects bc of fewer blood level peaks that are outside therapeutic range (and into toxic range)
true or false
adverse side effects are less frequent in modified release dosage forms
true
true or false
in modified release dosage forms, there is LESS fluctuation in blood drug levels
true
controlling the release rate eliminates the peaks and valleys in drug blood levels
true or false
an advantage of modified release dosage forms is that there is a reduction on overall healthcare costs
true
initial cost is greater, but there is enhanced therapeutic benefit and fewer side effects. also, healthcare personnel don’t have to dispense and administer the drugs as often and monitor the patients as often – saving money
true or false
modified release dosage forms require more frequent administration
false - less frequent
extended release products frequently deliver more than a single dose - thus taken less than conventional dosage forms
explain how modified release dosage forms leads to enhanced compliance and convenience
enhanced patient compliance because there is less frequent dosing
enhanced conveniene with day and night administration – not midday
what is the difference between SR and SA
sustained release - related to how much drug comes out
sustained action - related to the therapeutic effect
enteric coating is an example of what kind of modified release
timed release - want to release in small intestine and not stomach or delayed release
define modified release
the drug-release is based on the time, course, and/or location designed to accomplish therapeutic objectives or convenience objectives that are not offered by conventional or immediate release forms
define extended release
allows a reduction in dosing frequency
define delayed release
designed to release the drug at a time other than promptly after administration
ie - based on environmental factors like the low gastric pH
what are repeat action dosage forms?
contain 2 single doses of medication - one for immediate release and the 2nd for delayed release
true or false
enteric coating is an example of providing extended release
false - delayed release
what is targeted release
drug gets released at receptor site and not in circulation
ie: chemo drugs we dont want to get released in circulation so they are loaded in a nano particle and released at the receptor compartment
in modified release dosage forms, what has solvent action on the coated drug particles and thus controls the amount of drug released out?
the biologic fluids
the release rate of osmotic systems is controlled by what?
the diffusion of biologic fluids through a polymer
the release rate of erodible systems is controlled by…
the erosion of a polymeric matrix
ie: if polymer doesnt erode, the drug won’t come out
the release rate of diffusion systems is controlled by what?
the diffusion of the drug through a polymeric membrane or a monolithic matrix
true or false
in modified release dosage forms, chemical interactions can control the release of certain drugs
true
ie: interaction between the drug and site-specific biologic fluids (pH)
for oral rate-controlled products, a good drug candidate must have what kind of absorption and excretion and why?
neither very slow nor very fast absorption and secretion
not very slow because this drug would already be long acting and exhibit sustained release, so there’s no point
cannot be very fast because we would need an extremely high dose to provide a rate-controlled product and this tablet would be way too big to swallow
true or false
a good candidate for extended release products must be uniformly absorbed from the GI tract
true
a good drug candidate for extended release dosage form should be administered in relatively ____ doses
small doses
if it was large doses, tablet would be too big to swallow
why must drugs that are being considered to be made into extended release have a good margin of safety
technology limits and patient misuse
technology for extended release cannot realistically be so precise. thus, using a drug with a narrow therapeutic index would be dangerous
if pt chews on accident - immediately toxic
drugs that are good candidates for extended release products must treat what kind of conditions and why?
chronic conditions
acute conditions require more dosing adjustment by the physician and ER products can’t provide this
drugs with _ half lives are not good candidates for extended release dosage form
short
large quantity of drug would be required for formulation - too big to swallow
to be a good candidate for extended release dosage form, do we want it to exhibit active or passive absorption and why?
PASSIVE bc it will cover the entire GI tract
active only takes place in the duodenum
what should be the dose size for a drug to be a good candidate for extended release dosage form
0.5-1g
total daily dose can’t be higher than 1 g
to be a good candidate for extended release, what should the solubility of the drug NOT be
no less than 0.01mg/mL
the variation of the drug will be huge - sometimes release fast and sometimes slow
name 3 factors that affect GI transit time
floating systems
bioadhesives
penetration enhancers
what is a multitablet system?
small spheroid compressed tablets 3-4mm in diameter prepared to have varying drug release characteristics.
8-10 of these spheroid minitablets contained in a capsule with a gelatin shell. some of these minitablets are uncoated for immediate release and others are coated for extended release
the multitablet system is an extended release technology for the oral dosage form.
it consists of ___ inside ____
8-10 minitablets inside a capsule
what is the commercial name for repeat action tablets?
explain what they are
repetabs
initial drug dose is released from the tablet SHELL and then a second dose is released from the inner core of the tablet at a later time
type of extended release oral technology
what are “coated beads, granules, and microspheres”?
a type of extended release technology for the oral dosage form.
consists of either beads or granules. some are uncoated (immediate release and water soluble)
and some are coated with a LIPID MATERIAL (beeswax) and CELLULOSIC MATERIAL (ethylcellulose) in different thicknesses - comprises the SUSTAINED RELEASE DOSE
these coated beads or granules are either placed in to capsules or compressed into tablets
in coated beads/granules/microspheres extended release systems, the sustained release beads/granules consist of what material?
a lipid material like beeswax and cellulosic material like ethylcellulose in different thicknesses
give 4 examples of coated beads/granules/microspheres in the market
what is similar with all of them?
Toprol-XL (metoprolol succinate) tablets
Indocin SR (Indomethacin) capsules
Compazine (prochlorperazine) Spansule capsules
Adderall XR (amphetamine) capsules
they all contain 2 kinds of beads/granules: sustained release and immediate release
true or false
in the system with coated beads/granules/microspheres, the immediate release dose is coated with a hydrophilic material
FALSE - IT IS UNCOATED, but it is hydrophilic. that’s how it’s able to give immediate release
what is a micro-encapsulated drug?
an extended release technology for oral dosage form
solids, liquids, or gasses can be encapsulated into microscopic particles by the formation of thin coatings of wall material around the substance
(similar to an emulsion)
give 4 examples of the wall materials that can be used to coat the solid/liquid/gasses to form a microencapsulated drug for oral extended release
gelatin
PVA (polyvinyl alcohol)
ethylcellulose
polyvinyl chloride
give 3 examples of commercial products that give an extended release profile by using microencapsulation technology
Micro-K
K-dur
effexor XR (venlafaxine)
a form of technology for oral extended release is to embed the drug in…..
a slowly eroding or hydrophilic matrix system
in the technology of embedding the drug into a slow eroding or hydrophilic matrix system, explain how it works to given extended release
the IR dose is untreated and the sustained release dose is combined with a lipid or cellulosic material and processed into granules.
both of these portion are either placed into capsules, or compressed into 2 or 3 layered tablets
give 4 examples of extended release products on the market that use the technology of embedding the drug in a slowly eroding or hydrophilic matrix system
Slow-K
Depakote ER (divalproex sodium)
Quinidex (Quinidine Sulfate)
Oramorph SR (morphine sulfate)
True or false
a hydrophilic matrix system is unable to provide extended release
false - it can
in the extended release technology method of embedding the drug in a slowly eroding or hydrophilic matrix system, what type of erosions can occur and which is preferred?
surface erosion and bulk erosion
surface erosion - entire system gets smaller and smaller
bulk erosion - system breaks into smaller systems
surface erosion is preferred
technology: embedding drug in inert plastic matrix to provide extended release
explain how it works
the drug is combined with an inert polymer (PVA, polyethylene, and polymethacrylate) and processed into GRANULES
these granules are compressed into tablets.
The drug releases by a DIFFUSION MECHANISM through the polymer matrix
this is like solid dissolved in solid
technology: embedding drug into inert plastic material to provide extended release
give 3 examples of what this inert plastic material can be
PVA - polyvinyl acetate
polyethylene
polymethylacrylate
give 2 examples of extended release products that use the technology of embedding the drug in an inert plastic matrix
Gradumet
Procanabid
true or false
the extended release technology of embedding the drug in an inert plastic matrix is different from the other technologies in that the mechanism is via diffusion across the hydrophobic polymer matrix
true
the matrix is hydrophobic so it will not undergo dissolution (dissolve) in the body fluids
in the extended release technology of embedding the drug in an inert plastic matrix, what can you say about the solubility of the drug in the polymer?
should be water soluble enough to be able to diffuse into body fluids, but also be soluble enough in the polymer that enough drug can be loaded into it
explain the “complex formation” extended release oral technology
the drug is chemically combined with another agent like CYCLODEXTRIN to form a chemical complex
the hydrophobic drug (or hydrophobic portion of it) is maintained in the hydrophobic core of cyclodextrin.
the drug gets released into body fluids due to pH. ionization will take place in the core – which causes the hydrophobic properties of the core to decrease
the drug is released bc it doesn’t wanna stay in the ionized core – HAPPENS SLOWLY (extended release)
THE DRUG MUST COME OUT OF THE COMPLEX TO HAVE THERAPEUTIC EFFECT
give 4 examples of drugs that use complex formation technology in order to have extended release
are these drugs totally maintained in the hydrophobic core?
only the hydrophobic portion of these drugs is in the core and the hydrophilic portion is outside of it
ampicillin
progesterone
estradiol
prostaglandin F
what are ion exchange resins?
an oral extended release technology
explain how ion exchange resins work to provide extended release
a cationic or anionic drug (doesnt matter just has to be ionized) is combined with an ion exchange resin to form a resin-drug complex. this complex is encapsulated or tableted.
the electrolyte concentration and pH in the GI tract causes drug release into body fluids
in ion exchange resins, generally, drug release is greater…….
greater in the stomach than in the intestine
give 2 examples of products that use ion exchange resins in order to give extended release
Tussionex and Ionamin
if the drug is cationic, what will the resin be made of?
if the drug is anionic, what will the resin be made of?
cationic - SO3-
anionic - N(CH3)3+
what are the drug-resin complex particle treated with?
polyethylene glycol
what is the coating around the entire ion exchange resin?
ethylcellulose coating
if the drug is cationic, explain its release via ion exchange resin
extended release
the drug will be released by the effect of pH and electrolyte concentration in GI fluids. Drug will be released and hydrogen ions will go in
ion exchanged for ion
if a drug is anionic, explain its release via an ion exchange resin
extended release
drug will be released from the resin due to electrolyte conc and pH in GI tract.
anionic drug will be released and exchanged for chloride
what does OROS stand for
osmotic controlled release oral delivery system
what is the OROS system composed of?
a core tablet with a semipermeable coating.
there is a 0.4mm diameter hole for the drug to exit the tablet
in an osmotic pump, what is the drug release dependent on?
what is it independent on?
dependent on osmotic pressure
INDEPEDENT of the pH of biologic fluids
true or false
an osmotic pump is technology that is able to provide oral extended release
truw
in an osmotic pump, what is drug release CONTROLLED BY
the surface area
nature of the membrane
the diameter of the drug release orifice
true or false
zero order release is not attainable for an osmotic pump
FALSE - it is
name 3 advantages of osmotic pumps
the release is INDEPENDENT of the environment
for different drugs, reformulation is NOT required
can provide zero order drug release
name 2 disadvantages of an osmotic pump
these systems can be very expensive
quality control is more extensive
what is the diameter for the orifice where the drug is released in an osmotic pump
0.4mm
give 4 examples of products that use an osmotic pump to provide oral extended release
acutrim
Procardia XL
Glucotrol XL (glipizide)
Covera HS (verapamil)
osmotic pumps have similar technology to…..
transdermal delivery systems
somehwat replaced them
