Lecture 15/16

Question 1

controlled drug delivery types

Answer 1

temporal
spatial

Question 2

temporal

Answer 2

sustained release (delayed or extended) or pulsatile release

Question 3

spatial

Answer 3

systemic, local, or targeted

Question 4

potential advantages of CDD

Answer 4

maintain optimum drug concentrations
improve efficiency of treatment with less amount of drug
minimize side effects
less frequent administration
increase patient convenience and compliance with dosing regimen (adherence)

Question 5

disadvantages of CDD

Answer 5

relatively high production costs
leakage of drug mass (aka drug dumping)
difficult to stop drug release
biocompatibility of the delivery systems?
necessity of surgical operation

Question 6

temporal needed fro

Answer 6

optomizing drug concentration-time profiles at the site of action
reducing administration frequency of the drugs
simulating multiple dosing via combination of an immediate-release dosage and a pulsatile delivery system

Question 7

temporal not needed for

Answer 7

drugs with a long half-life
drugs of which long-term effect is undesirable
drugs which require immediate effect

Question 8

drug release control mechanisms

Answer 8

diffusion-controlled systems (reservoir and matrix devices)
dissolution-controlled systems
erosion-controlled systems
osmotic systems
swelling systems

Question 9

diffusion-controlled systems

Answer 9

drug diffusion through the polymer network is the rate limiting step
either reservoir systems (release rate controlling membrane) or matrix/monolithic systems

Question 10

ocusert

Answer 10

a reservoir of pilocarpine that goes in the eye

Question 11

norplant

Answer 11

non-erodible subdermal implant contraceptive; silicone capsules containing levonorgestrel
trocar injections into forearm
discontinued in Us due to menstrual disturbances and other factors (pain, scar tissue, appearance, feel)

Question 12

tetracycline peridontal fibers

Answer 12

provides tetracycline in a polymer membrane in periodontal (gum) therapy

Question 13

Drug release from diffusion-reservoir equation

Answer 13

M (amount of drug flowing through a membrane) =
D (diffusion coefficient) x
S (cross section area, cm^2) x
K (partition coefficient) x
Cs (drug concentration in reservoir) x
t (time)
/
h (thickness of membrane)

Question 14

nicotine patch components

Answer 14

occlusive backing (clear)
drug reservoir
rate-controlling membrane
adhesive and release liner

Question 15

drug release from diffusion-matrix

Answer 15

drug and matrix former are not physically separated
drug release depends on the device geometry
gradient
example - habitrol patches

Question 16

diffusion-matrix equation

Answer 16

M =
S (area of the device) x
[ Cs (drug’s solubility in the polymer x
D (diffusion coefficeint) x
(2Co (total drug concentration) - Cs) x
t (time) ] ^1/2

Question 17

higuchi equation

Answer 17

M = kt^1/2
log graph
large initial burst

Question 18

reservoir vs matrix in diffusion systems

Answer 18

reservoir - straight, constant graph (same as osmotic systems graph)
matrix - log graph with initial burst (flipped upside down for dm/dt)

Question 19

drug reservoir examples

Answer 19

types - membrane modulated (scopolamine and nitroglycerin in the transderm-nitro brand) and adhesive dispersion (nitroglycerin in deponit band)

Question 20

matrix drug examples

Answer 20

type - matrix dispersion (nitroglycerin in nitrodur brand)

Question 21

nexplanon/implanon NXT (merk)

Answer 21

approved in the us in 2006 flexible rod
drug + matrix/coating
initial burst to get to therapeutic window then constant release

Question 22

dissolution systems

Answer 22

encapsulated (polymer is released, 0 to 100) and matrix
graph is log for M and tilted to the right for dm/dt

Question 23

dissolution-matrix

Answer 23

hixson-crowell cube-root law (Mo^1/3 - Mt^1/3 = kt
surface area changes with dissolution of the drug and polymer matrix

Question 24

osmotic systems

Answer 24

film coating - permeable for water but not permeable for drug or excipients
rigid - resist the hydrostatic pressure to push out the drug
M is straight constant and

Question 25

drug release from osmotic systems equation

Answer 25

M =
t (time) x
[ (k (membrane permeability to water) x
s (area of membrane) ) /
h (thickness of membrane) ] x
deltaPi (osmotic pressure difference) x
Cs (drug concentration)

Question 26

osmotic plus additional release via simple diffusion

Answer 26

osmotic equation + DSKCsT/h (reservoir systems equation)

Question 27

erosion-controlled systems

Answer 27

initial release phase is controlled by diffusion of drug molecules that are on the surface or have access to the surface via pores
sustained-release phase is determined by erosion of polymer

Question 28

erosion-controlled system example drugs

Answer 28

zoladex
lupron
nutropin
gliadel wafer
sustol

Question 29

gliadel wafer

Answer 29

treats malignant glioma
short half life - under 15 min
dose limiting side effect (bone marrow suppression –> pulmonary fibrosis)
systemic administration is not desirable
temporal - released in time-controlled manner
spatial – released in the direct vicinity of the site of action

Question 30

lupron depot

Answer 30

treats prostate cancer
injected IM
1-4 month release for advanced prostate cancer to lower testosterone levels

Question 31

polymer swelling

Answer 31

length of the diffusion pathways increases leading to decreasing drug concentration gradients leading to decreasing drug release rate
mesh size of polymer increases leads to increasing drug diffusivities in the polymer network leads to increasing drug release rate