Lec 12- Reservoir systems Flashcards
1
Q
Classification
A
- Modified release dosage forms may be classified according to a number of different criteria
- Route of administration (e.g. oral, ocular)
- Type of release (e.g. delayed, sustained)
- Release mechanism (e.g. diffusion, dissolution)
- Technological system (e.g. reservoir, matrix)
2
Q
Controlled-release Mechanism
A
3
Q
Diffusion-controlled Devices
Membrane-controlled Reservoir Systems
A
- The drug is totally contained within a rate-controlling membrane
- Allows constant zero-order release rates (rate of drug release is consitent and not dependent on concentration of the drug) to be achieved
- An extended period of dosing
- Release over a substantial period of time
4
Q
Membrane-controlled reservior systems
Advantages
A
- advantages of choosing a reservoir-type system
- high level of loading
- drug can be a large part of device (~90%)
- efficient use of materials
- allows use of low potency drugs (you can use higher doses)
- High release rates achievable- these are achievable- tune the polymer you have (lower density, open pore-size etc)
5
Q
Membrane-controlled Reservoir Systems: Disadvantages
A
- Fabrication usually quite expensive
- Release rates depend upon:
- Membrane thickness, area, permeability
- Careful control of variables - increases the cost
- Materials usually expensive
- Release rates depend upon:
- Difficult to deliver high molecular weight compounds- pore size is the limitation (large particle small pore so drug gets trapped)
- Generally, have to be removed from the site
- Danger of dose-dumping
- Damage to membrane
6
Q
Membrane diffusion
A
- Diffusion: flow from a more concentrated to a less concentrated region
- The release is dependent on diffusion through the membrane
- Donor compartment (INSIDE THE DEVICE) and Receiver compartment (Outside)
- With concentration being in the donor the drug will flow down the concentration gradient going from high to low or donor to the receiver
*
- With concentration being in the donor the drug will flow down the concentration gradient going from high to low or donor to the receiver
7
Q
Membrane Diffusion
Fick’s First Law
A
- Flux (J) = Mass flow across membrane per unit time per unit area
- Change in mass / Area x change in time
- Use bottom left equation
8
Q
Control of drug release
A
Where
- dMt/dt= Rate of drug release (mass/time)
- A = Membrane surface area
- D = Diffusion Coefficient of drug in membrane
- K = Partition Coefficient of drug in membrane
- Cs = Concentration of drug in the donor compartment
- Cr = Concentration of drug in the receiver compartment
- h = Membrane thickness
9
Q
Membrane diffusion
Control of zero order release
A
- Under sink conditions (Cs>>Cr)- Much more drug in the donor, large gradient
- Use a large volume (more than needed to dissolve)
- The body always have sink conditions
- dM/dt = constant… when concentration gradient is held constant
10
Q
Membrane Diffusion
Zero Order Release
A
- Graph on the right is drug release rate, the release rate is stable
11
Q
Membrane Diffusion
Control of Zero Order Release
A
- Most of the time, the concentration gradient is held constant for a defined ‘life-time’ e.g. Ocusert eye inserts releases the drug for up to 7 days with zero-release kinetics (while there are sink conditions).
- Concentration gradient may be held constant to the main zero-release by:
- Use of a drug with limited solubility
- Formulate drug as a suspension (i.e. saturated solution) inside the reservoir
- Delivery of a small fraction of total drug in the reservoir (i.e. maintain excess)
12
Q
Duration of Constant Release Rate
A
- For zero-order release
- a constant concentration within the device must be maintained
- Lasts as long as there is undissolved solid within reservoir
- Eventually all solid dissolves and release rate falls
- a constant concentration within the device must be maintained
- This is the useful “life-time” of the device
13
Q
Duration of Constant Release Rate
A
- We can quantify the Duration of Constant Release tinfinity
- Mass of drug in the device at end of zero order period = Cs V
- The initial mass of drug = M0
- Mass of drug delivered = M0 – Cs V
- NB- don’t have to learn the equations
14
Q
Membrane-controlled Reservoir Systems-Release Profile
A
- Green line= zero order no change in release rate- steady state
- Red= Exhaustion- release rate starts to decline
*
- Red= Exhaustion- release rate starts to decline
15
Q
Non-steady state release
A
- Concentration in the membrane is less than that at steady state
- The recently manufactured device may take time to release the drug
- Slow release period, then the release rate increases until it reaches a steady state
16
Q
Storage effects lag period
For new devices
A
- In the new device, the concentration gradient is much lower due to the fact that it takes time for the drug to reach a steady state- we have not got zero order release yet as sink conditions have not been met
17
Q
Storage effects
Burst effects
A
- Burst effect- fast release
- As the drug on the surface is lost the release of the drug slows down as the remainder of the drug has to travel through the release controlling membrane, this slowing continues until a steady state (zero-order) release rate has been achieved
18
Q
Non-steady state release
Burst effect
A
- Concentration in the membrane is more than that at steady state
- BURST EFFECT
- Opposite to lag period
- Older device
- Due to long storage, drug starts to penetrate the reservoir membrane and cover the surface of the formulation- therefore there is no barrier between the drug and patient
- This leads to a steep increase in the mass of drug release
20
Q
Release from Devices
Effect of Geometry
A
- We have drug in the layer in the middle with the release layers at the top and bottom
- Use the same equation as before
- Consider change in the area
