Concepts and mechanisms of drug release

Question 1

What does the monolithic system consist of?

Answer 1

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

Question 2

What does the reservoir system consist of?

Answer 2

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

Question 3

What is microencapsulation?

Answer 3

coating of the surface of drug particles with a polymer to slow down water penetration and dissolution

Question 4

How are ion exchange resins used in drug release?

Answer 4

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.

Question 5

What is an advantage of ion exchange resins?

Answer 5

Reduces risk of dose dumping

Question 6

What are some ER formulations for Morphine?

Answer 6

film coated tablet, single dose sachets, pellets in a capsule shell, hard gelatine capsules containing multi-particulates

Question 7

What is the mechanism of release from a Continus tablet system?

Answer 7

Dissolution of the higher aliphatic alcohol and dissolution of the drug through the hydrated hydroxyalkyl cellulose

Question 8

What decides the rate of release in the Continus tablet system?

Answer 8

amounts of hydroxyalkyl celluloses and higher aliphatic alcohols plus extent of hydration

Question 9

What is the mechanism of release of MST Continus suspension granules?

Answer 9

morphine bound to ion exchange resin beads and is displaced by sodium and potassium ions in the GIT then free resin is excreted

Question 10

Why do we get slow-release form ion exchange granules?

Answer 10

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

Question 11

What is the mechanism of release of Zomorph modified release capsules (with pellets)?

Answer 11

Diffusion of the active material across the ethyl cellulose coat

Question 12

What determines the release characteristics of MR capsules with pellets?

Answer 12

Thickness of the ethyl cellulose coat

Question 13

What is the release mechanism of MXL capsules?

Answer 13

capsules disintegrates, water enters multiparticulates and morphine diffuses out of each particle

Question 14

Describe the structure of MXL capsules

Answer 14

Powdered morphine + hydrophobic wax (hydrogenated vegetable oil) and cooled to give multiparticulates. These are then encapsulated

Question 15

Why shouldn’t you crush or chew extended release tablets?

Answer 15

will result in uncontrolled delivery of morphine (dose dumping) and can lead to overdose or death.

Question 16

Describe the design of a transdermal patch

Answer 16

protective liner, adhesive formulation, drug-release membrane, drug reservoir, pigmented backing

Question 17

What are some advantages of transdermal drug delivery?

Answer 17

Simple & safer administration and termination of therapy. Avoids first pass metabolism, almost constant therapeutic concentrations over extended period, better patient compliance

Question 18

What are some disadvantages of transdermal drug delivery?

Answer 18

product more expensive, not all drugs can penetrate skin barriers, need to be potent as the size of the patch is small

Question 19

How is the skin structured?

Answer 19

epidermis, dermis, subcutaneous fat

Question 20

What is the function of the skin?

Answer 20

Barrier, support, thermal, cushion, insulation

Question 21

What are the possible routes for a drug to enter the skins?

Answer 21

intracellular, intercellular and shunt routes (into hair follicle or into sweat glands)

Question 22

What is the function of the stratum corneum?

Answer 22

the main barrier for drug delivery, also prevents water loss from skin, is like amphoteric gel

Question 23

What is the dermis composed of?

Answer 23

collagen, elastin, polysaccharides and is very water rich

Question 24

What is the function of the dermis?

Answer 24

has blood supply, helps maintain temperature, can remove permeating solutes and has nerve supply. Dermis is more hydrophilic, sink conditions for drug

Question 25

What sort of substances permeate the skin well?

Answer 25

quite polar, amphiphilic (log P 1-5), unionised, tendency to form hydrogen bonds, low MW

Question 26

What factors can increase permeation?

Answer 26

hydration of skin, higher temp, broken or peeled skin

Question 27

What are the types of TDS and explain how they work

Answer 27

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

Question 28

What are the basic components of a patch?

Answer 28

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

Question 29

What is the criteria for designing a transdermal delivery system?

Answer 29

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

Question 30

How can you maximize drug delivery?

Answer 30

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

Question 31

What are some adhesive characteristics?

Answer 31

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

Question 32

Why is fentanyl ideal for transdermal delivery?

Answer 32

soluble in both fat and water, has a low molecular weight and high potency

Question 33

How can you formulate a BCS class IV compound like amphotericin B?

Answer 33

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