Concepts and mechanisms of drug release Flashcards
What does the monolithic system consist of?
Wax matrix, a drug dispersed in a wax system, drug release occurs via GI fluid permeating matrix allowing drug to dissolve. Hydrophilic system: system swells to form a gel or viscous matrix (with presence of GI fluid) which controls water uptake and diffusion of drug through gel layer or via erosion
What does the reservoir system consist of?
polymeric membrane surrounding drug core and diffusion occurs through membrane coating, osmotic pump: drug stored in an osmotic core surrounded by a polymeric membrane with a tiny hole to allow release of drug on swelling caused by a build of osmotic pressure as water diffuses into core
What is microencapsulation?
coating of the surface of drug particles with a polymer to slow down water penetration and dissolution
How are ion exchange resins used in drug release?
High electrolyte concentration exchanges the drug for another counter ion. Incorporate resin-drug complex (which binds via electrostatic interaction) with protein on the outside, done by incubation or passing through column.
What is an advantage of ion exchange resins?
Reduces risk of dose dumping
What are some ER formulations for Morphine?
film coated tablet, single dose sachets, pellets in a capsule shell, hard gelatine capsules containing multi-particulates
What is the mechanism of release from a Continus tablet system?
Dissolution of the higher aliphatic alcohol and dissolution of the drug through the hydrated hydroxyalkyl cellulose
What decides the rate of release in the Continus tablet system?
amounts of hydroxyalkyl celluloses and higher aliphatic alcohols plus extent of hydration
What is the mechanism of release of MST Continus suspension granules?
morphine bound to ion exchange resin beads and is displaced by sodium and potassium ions in the GIT then free resin is excreted
Why do we get slow-release form ion exchange granules?
may get very quick priming dose on the outside of the bead but diffusion has to occur through the beads and through the pores, displaced drug has to come out of the bead which is a slow process
What is the mechanism of release of Zomorph modified release capsules (with pellets)?
Diffusion of the active material across the ethyl cellulose coat
What determines the release characteristics of MR capsules with pellets?
Thickness of the ethyl cellulose coat
What is the release mechanism of MXL capsules?
capsules disintegrates, water enters multiparticulates and morphine diffuses out of each particle
Describe the structure of MXL capsules
Powdered morphine + hydrophobic wax (hydrogenated vegetable oil) and cooled to give multiparticulates. These are then encapsulated
Why shouldn’t you crush or chew extended release tablets?
will result in uncontrolled delivery of morphine (dose dumping) and can lead to overdose or death.
Describe the design of a transdermal patch
protective liner, adhesive formulation, drug-release membrane, drug reservoir, pigmented backing
What are some advantages of transdermal drug delivery?
Simple & safer administration and termination of therapy. Avoids first pass metabolism, almost constant therapeutic concentrations over extended period, better patient compliance
What are some disadvantages of transdermal drug delivery?
product more expensive, not all drugs can penetrate skin barriers, need to be potent as the size of the patch is small
How is the skin structured?
epidermis, dermis, subcutaneous fat
What is the function of the skin?
Barrier, support, thermal, cushion, insulation
What are the possible routes for a drug to enter the skins?
intracellular, intercellular and shunt routes (into hair follicle or into sweat glands)
What is the function of the stratum corneum?
the main barrier for drug delivery, also prevents water loss from skin, is like amphoteric gel
What is the dermis composed of?
collagen, elastin, polysaccharides and is very water rich
What is the function of the dermis?
has blood supply, helps maintain temperature, can remove permeating solutes and has nerve supply. Dermis is more hydrophilic, sink conditions for drug
What sort of substances permeate the skin well?
quite polar, amphiphilic (log P 1-5), unionised, tendency to form hydrogen bonds, low MW
What factors can increase permeation?
hydration of skin, higher temp, broken or peeled skin
What are the types of TDS and explain how they work
reservoir system release is controlled by diffusion through the membrane, tighter control but higher risk of dose dumping. Matrix system release is controlled by diffusion through polymer matrix
What are the basic components of a patch?
drug in a polymer matrix or reservoir, penetration enhancers, (e.g. SLS, interaction with stratum corneum to alter structure), adhesive, protective release linear, outer backing laminate
What is the criteria for designing a transdermal delivery system?
constant delivery rate, non-irritating adhesive and vehicle, vehicle should have properties allowing quick release of drug, system should occlude the skin to ensure one-way flux of drug
How can you maximize drug delivery?
Have drug at its saturation solubility in the vehicle, Use a vehicle which modifies the skin barrier, vehicle with low affinity for drug (enabling drug to partition into SC), choose skin site with low thickness
What are some adhesive characteristics?
Should allow migration of active drug, Should enable the device to adhere to contours and flexible points of the skin, contains active ingredient to act as quick priming dose, should enable device to remain on the skin for a specified period of time
Why is fentanyl ideal for transdermal delivery?
soluble in both fat and water, has a low molecular weight and high potency
How can you formulate a BCS class IV compound like amphotericin B?
Nanoparticle technology using lipid-based formulations by encapsulating drug into lipid vesicles, the liposomes are too big for glomerular filtration/renal elimination so amphotericin B less likely to contact distal tubuli cells reducing the potential for nephrotoxicity
