MRDFs Flashcards
What is the meaning of the acronym MTC?
Maximum therapeutic concentration
What is the meaning of the acronym MEC?
Minimum effective concentration
What is the therapeutic window?
This is the range of drug concentration in the body that is within the MTC (maximum therapeutic concentration) to the MEC (minimum effective concentration)
What is the duration of action?
This is the time spent when drug concentration is above MEC (minimum effective concentration)
What are some challenges associated with conventional release?
Do not maintain blood concentration within therapeutic window for an extended period of time
AND
Controlled drug release is not possible
What is the rational for MRDFs?
To prolong or control drug availability or release with the intent of improving efficacy of drug therapy
What are the different types of MRDFs?
Sustained release (SR)
TImed release (TR)
Time Delay (TD)
Prolonged action (PA)
Controlled release (CR)
Repeat action
Extended release (ER)
Long acting (LA)
Targeted release
Describe extended release systems
Allow reduction in dosing frequency from that necessitates by a conventional dosage form
Describe delayed-release systems
They release the drugs at a time other than promptly after administration. They delay may be influenced by pH (like enteric formulations)
What is targeted release (TR)?
This formulation effectively isolates or concentrates drugs in a specific body region, tissue, or organ (tumour therapy may employ this formulation)
What is repeat action in terms of drug release systems?
They usually contain two or more single doses of the drug, one for immediate release and the second for delayed release
Ex. Concerta
What are some examples of a delayed action formulation?
Enteric coated
Rheumatoid arthritis
Morning sickness (releases during sleep so it is effective in the morning)
What is the rationale for extended release formulations?
These formulations provide an immediate release of drug (“loading dose-ish” brings drug concentration above MEC), and it is followed by gradual and continual release of additional amounts of drug to maintain its effect over a period of time
This effectively reduces the frequency of dosing
What is the difference between controlled and extended release?
Controlled release: constant rate of release
Extended release: variable rate of release (faster at start, gradual over time)
What is the difference between sustained release and extended release?
It is the duration of action
Extended release is usually a higher dose, but remains effective for a longer period of time vs. the sustained release formulation
What are some advantages of MRDFs?
Less fluctuation in drug levels
Reduced dosing frequency
Enhanced patient adherance
Reduction in adverse side effects
Potential reduction in indirect health care costs due to the above advantages
What are some limitations of MRDFs?
Initial cost is high
Immediate termination of drug action is not possible
Contain higher amount of active ingredient (abuse potential)
Higher probability for drug-excipient interaction
More complex formulation design
Not suitable when rapid action is required
Not flexible (cannot split)
What are some variables that are considered in the design of MRDFs?
All of the following variables are interrelated:
Route of delivery
Type of delivery system
Disease being treated
The patient (age, sex, individual variation)
Length of therapy
Properties of the drug (physiochemical, biological)
What is the desired water solubility in MRDFs?
We need to use drugs with intermediate water solubility
If low solubility, takes too long to dissolve and have hard time diffusing through polymer shell
If high solubility = hard to reduce dissolution rate
What is the significance of partition coefficient in MRDFs?
It is the potential of drugs to cross biological membrane (ratio of drug in lipid vs. aqueous phase)
This property affects the ability of the drug to diffuse through the polymers used in the design of MRDFs
What is stability requirements for MRDFs?
The drug needs to remain stable in the dosage form while OUTSIDE the body
The drug also needs to be stale in the dosage form INSIDE the body (penetrating fluids should not degrade the drug)
What pharmacokinetic properties are preferred in MRDFs?
Intermediate ADME is preferred
Slow kinetics (do not need to formulate into MRDFs)
Fast kinetics (very short half-life, need large amounts of drug to design MRDFs bc by extending duration of action, that is more time for the unreleased drug to be subject to ADME)
Are drugs that bind to plasma proteins good candidates for formulation into MRDFs?
No, only free unbound drug can diffuse through tissues and hence can be controlled
Are drugs with wide therapeutic indexes ideal fro formulation into MRDFs?
Yes, there is not a concern about accidental immediate release
Avoid using drugs that have narrow therapeutic indices
Are oral MRDF doses smaller or bigger compared to conventional release oral formulations?
They are bigger because MRDFs must store more drug in a larger tablet or capsule.
A larger tablet/capsule may increase difficulty of swallowing = reduced patient compliance
What is the principle of dissolution systems in MRDFs?
Controlled release products are prepared by controlling the dissolution rate of drugs that are readily soluble
What are the two types of dissolution systems in MRDFs?
Membrane dissolution systems
Matrix dissolution systems
Describe Membrane Dissolution Systems
Type 1:
Different groups of particles with different membrane thickness and composition are made and contained in a tablet/capsule
Type 2:
A layer of drug is coated on a sugar core and then coated with slowly dissolving membrane (alternating membrane and drug, like Matryoshka doll). The outer-most layer is a layer of drug that can be immediately releases as the loading dose
Due to these difference, each granule will release drug at different rates or times
Describe Matrix Dissolution Systems
Drug is disperse in a series of different sized granules (no discernible core) made of the matrix material
These matrix granules often are combines with granules with no matrix material (effectively providing a loading dose)
What is the principle behind diffusion systems?
Release rate of drug is determined by its diffusion through a water-insoluble polymer
What are the two types of diffusion systems?
- Membrane Diffusin (Reservoir devices): core is surrounded by a polymeric membrane
- Matrix Diffusion (Matrix device): drug is distributed uniformly in an inert polymeric matrix
What are matrix diffusion devices?
The drug is dispersed homogeneously in the matrix which DOES NOT dissolve or erode (unlike dissolution systems)
The drug diffuses from the matrix to outside
How do osmotic systems control the release rate of drug?
Osmotic pressure is used to swell a membrane, causing it to push drug through an orifice. The rate at which the membrane expands and the size of the orifice can impact drug release rate
Can immediate release and MRDFs formulations of the same drug be used interchangeably?
No, patients stabilized on a MRDF should not be changes to an immediate release product without consideration of any existing blood level concentrations of the drug
Can MRDFs be crushed to chewed for easier swallowing?
No, this will compromise the unique drug release features
Are empty shells in stool while on MRDFs an issue?
No, they are usually non-erodible and it is common to see them in the stool
What is the only situation where pharmacists can switch a patient from one MRDF to another MRDF of the same drug?
When the prescribed MRDF is unavailable, we may use another MRDF as a temporary substitute
Use the MRDF substitute that can give the most similar dose vs. time curve
