Lecture 15/16 Flashcards
principles of controlled drug delivery (2/27, 2/29)
controlled drug delivery types
temporal
spatial
temporal
sustained release (delayed or extended) or pulsatile release
spatial
systemic, local, or targeted
potential advantages of CDD
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)
disadvantages of CDD
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
temporal needed fro
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
temporal not needed for
drugs with a long half-life
drugs of which long-term effect is undesirable
drugs which require immediate effect
drug release control mechanisms
diffusion-controlled systems (reservoir and matrix devices)
dissolution-controlled systems
erosion-controlled systems
osmotic systems
swelling systems
diffusion-controlled systems
drug diffusion through the polymer network is the rate limiting step
either reservoir systems (release rate controlling membrane) or matrix/monolithic systems
ocusert
a reservoir of pilocarpine that goes in the eye
norplant
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)
tetracycline peridontal fibers
provides tetracycline in a polymer membrane in periodontal (gum) therapy
Drug release from diffusion-reservoir equation
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)
nicotine patch components
occlusive backing (clear)
drug reservoir
rate-controlling membrane
adhesive and release liner
drug release from diffusion-matrix
drug and matrix former are not physically separated
drug release depends on the device geometry
gradient
example - habitrol patches
diffusion-matrix equation
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
higuchi equation
M = kt^1/2
log graph
large initial burst
reservoir vs matrix in diffusion systems
reservoir - straight, constant graph (same as osmotic systems graph)
matrix - log graph with initial burst (flipped upside down for dm/dt)
drug reservoir examples
types - membrane modulated (scopolamine and nitroglycerin in the transderm-nitro brand) and adhesive dispersion (nitroglycerin in deponit band)
matrix drug examples
type - matrix dispersion (nitroglycerin in nitrodur brand)
nexplanon/implanon NXT (merk)
approved in the us in 2006 flexible rod
drug + matrix/coating
initial burst to get to therapeutic window then constant release
dissolution systems
encapsulated (polymer is released, 0 to 100) and matrix
graph is log for M and tilted to the right for dm/dt
dissolution-matrix
hixson-crowell cube-root law (Mo^1/3 - Mt^1/3 = kt
surface area changes with dissolution of the drug and polymer matrix
osmotic systems
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
drug release from osmotic systems equation
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)
osmotic plus additional release via simple diffusion
osmotic equation + DSKCsT/h (reservoir systems equation)
erosion-controlled systems
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
erosion-controlled system example drugs
zoladex
lupron
nutropin
gliadel wafer
sustol
gliadel wafer
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
lupron depot
treats prostate cancer
injected IM
1-4 month release for advanced prostate cancer to lower testosterone levels
polymer swelling
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
