MRDF Flashcards
Based on the conventional release profile, what are the challenges you identify for drug action?
conventional dosage forms do not maintain blood concentration within therapeutic range for extended period of time and
controllable drug release is not possible
What does MEC?
minium effective concentration
What is MTC?
Minimum toxic concentration
if drug level have to be maintained using conventional dosage forms what are the two approaches?
increase initial dose to increase duration of actions
administer the drug repeatedly using a constant dosing interval
What is the consequence of increasing initial dose?
increase potential of toxicity
What is the consequence of repeated drug administration
missed doses or
made up doses or
pt non-compliance
What is the rationale for MRDFs?
to prolong or control drug availability or release with the intent of improving efficacy of drug therapy
What is the two major types of MRDFs?
delayed action
extended action
Define delayed action
lag period between admin. and release
release the drug at particular site
mostly enteric coated
Define extended action
release the medication in a controlled manner at a predetermined rate, duration and location to achieve and maintain therapeutic blood levels
What does sustained release systems include?
any drug delivery system that achieves slow release of drug over extended period of time
What is needed to consider it a controlled release system?
if a sustained release system is successful at maintaining constant drug levels in the target organs
What is needed to consider it a prolonged release system?
prolongs therapeutic levels of the drugs
What is the purpose of extended release systems?
allows reduction in dosing frequency
What is the purpose of delayed release systems?
it can release the drug at a time other than promptly after administration
Define targeted release
isolates or contrates the drugs in specific body region, tissue or organ
What is an example of targeted release?
tumor nanomedicine - targeted drug delivery
what is repeat action?
forms usually contain two or more single doses of the drug, one for immediate release and the second for delayed release
What are the examples for preparing delayed action formulation?
entric coated
rheumatoid action
morning sickness
What is the rationale for extended release?
provides an immediate release, giving the effect now as well as by the gradual and continual release of additional amounts of drug
T/F Controlled release are therefore extended release formulations
True
What is the difference between SR and XL?
it is different in the duration of action
List somes advantages of MRDFs
less fluctuation of drug levels
reduced dosing frequency
enhanced pt compliance
reduction in A/E
reduced in health care cost
List some limitations of MDFS
costly
immediate termination of drug action is not possible
contains higher drug amounts (abuse potential)
drug excipient interaction
more complicated formulation design
not suitable for rapid action (Emergency use)
not flexible (cannot split)
To have the equvient dose how many doses in the day with IR, SR and XR
IR - TID
SR - BID
XR - Once daily
List the variables in the design
route of delivery
type of delivery system
disease being treated
the patient
length of therapy
properties of the drug (physicochem/bio)
What factors are considered when the drug has low water solubility?
longer time to dissolve in GI fluids
slower absorption
inherently extended release
What factors are considered when the drug has high water solubility?
difficult to reduce their dissolution rate to an acceptable range
Define partition coefficient
potential of drugs to cross biological membrane
What does partition coefficient affect?
the ability of the drugs to diffuse through the polymers used in the design of MRDFs
What two factors need to be balanced with stability>
the stability of the drug inside and outside of the body
Explain the slow kinetics
inherently long acting
not necessary to prepare MRDFs
Explain the fast kinetics
very short half lives
very large amounts will be required to design MRDF
What are the two factors need to look at for rate of absorption and excretion?
slow kinetics or fast kinetics
Explain the ability of drugs for complexation
drugs which show high levels of protein binding in the blood are not suitable for MRDFs
T/F Only free unbound drugs can diffuse through tissues and hence can be controlled
True
What needs to be looked at for a good margin of safety?
therapeutic window –> it can not be narrow as it has a risk of dose dumping if the product is defective or incorrectly administered
Should MRDFs be used for chronic conditions or acute? Why?
acute –> as more dosage adjustments are required
and immediate use of the medications
What should be considered for dosing for MRDFs?
If conventional formulation has a large dose larger sized tablets and capsules required to design MRDFs difficult swallowing reduced patient compliance
What is the max dose for oral formations?
0.5-1 gram
List the mechanisms for modified release
membrane dissolution
membrane diffusion
matrix dissolution
matrix diffusion
membrane-matrix hybrids
osmotic pressure
What categories do most products fall into?
membrane dissolution systems
matrix dissolution systems
Define dissolution systems
Controlled release products are prepared by controlling the dissolution rate of drugs that are readily soluble.
T/F uncoated particles = immediate release form of drugs
True
Explain the two types of membrane dissolution systems
different groups of particles with different membrane thickness and composition are made, that will release the drug at different rates or times.
a layer of drug is coated by sugar core
then coated with slowly dissolving membrane
another layer of drug that another coat
(the outer layer is the loading dose)
Explain Layered tablets
Layered technology
Immediate burst and prolonged release layered dissolution
Explain matrix dissolution systems
drug is dispersed in a series of different size granules
the different size will have different dissolution times
What are two types of diffusion systems?
membrane diffusion
matrix diffusion
Explain diffusion systems
release rate of drug is determined by its diffusion through a water insoluble polymer
Explain membrane diffusion
core is surrounded by a polymeric membrane
reservoir devices
Explain matrix diffusion
drugs is distributed uniformly in an inert polymeric matrix
matrix device
Explain how reservoir devices
drug release usually involves
- dissolution of drug inside the reservoir
- diffusion of drug across membrane - rate controlling step
What is the rate limiting step with matrix diffusion devices?
diffusion of the drug from the matrix to outside
Explain how a matrix diffusion device works
drug is dispersed homogeneously in the matrix which does not dissolve or erode
What are some examples of membrane-matrix hybrid?
mirena IUD
nuva ring
Define osmotic systems
it uses osmotic pressure can be employed as the driving force to generate a constant release of drug, provided that constant osmotic pressure is maintained
Explain how osmotic pressure works to help with MDRFs
Water moves in –> dissolves or suspends the drug –> membrane is not permeable to the drug –> the system pushes the drug out through the orifice
What are some counselling points for MRDFs?
- Advise the patients of the dose and dosing frequency of modified drug release products
- Advice the patients not to use them interchangeably with immediate release of the same drug
- Patients stabilized on a modified-release product should not be changed to an immediate release product
- Once stabilized, patients should not be changed to another extended-release product unless there is assurance of equivalent bioavailability.
- capsules should not be crushed or chewed
- pt fed by an NG feeding tube may receive conventional or modified release
- empty shells may be seen in the stool
