controlled release drugs Flashcards
role of small intestine
main site of absorption and gastric uptake
role of duodenum
regulates supply of material to the small intestine
persorption
mode of permeation across the intestinal wall, cells are sloughed off during digestion leaving gaps so the drug can slip into circulation
drug classification I
high solubility and permeability
drug classification II
low solubility and high permeability
drug classification III
high solubility and low permeability
drug classification IV
low solubility and permeability
high solubility
highest dose soluble in <250ml water over 1-7.5pH
high permeability
extent of absorption in humans is >90% of administered dose
uncontrolled delivery
no formulation constraint on the release of the drug from delivery system
controlled delivery
a formulation constraint on the release of the drug from the delivery system
structure of monolith devices
solid, all in one matrix that is hydrophobic (implants) or hydrophilic (gel layer formed on contact with water) usually made with hydroxypropyl methyl cellulose
how do monolith devices work
hydroxypropyl methyl cellulose hydrates in contact with water to form a viscous gel, drug diffuses out and matrix erodes
kinetics of monolith devices
zero order, square root relationship between drug release and time
structure of membrane limiting systems
film coated, housed by a reservoir with a membrane limiting release, ethyl cellulose or eudragits - dose dumping!
how do membrane limiting systems work
water in - drug out, immobile until water penetrates and forms a channel in which the drug can diffuse out
structure of osmosis controlled systems
water insoluble core containing active drug and insoluble semi-permeable coating
how do osmosis controlled systems work
osmotic pressure used to pump drug out at a constant rate, core materials undergo dissolution, suspension and solubilisation
advantages of osmosis controlled systems
cheap, compatible with lots of drugs, zero order release
disadvantages of osmosis controlled systems
expensive to drill, precise, integrity and consistency of coating is important
structure of multi-particulate systems
multiple units typically loaded into a capsule
how do multi-particulate systems work
multiple units in one capsule, same rate limiting film as membrane limiting systems
advantages of multi-particulate systems
dose dumping less likely, consistent GI transit and reduced irritation
disadvantages of multi-particulate systems
high cost and some technical issues
types of gastroretentive systems
effervescent, bio adhesive and swelling
structure of effervescent gastroretentive systems
low density systems that generate gas and float - sodium alginate/carbonate
structure of bioadhesive gastroretentive systems
adhere to biological membranes to form a protective layer
structure of swelling gastroretentive systems
superporous hydrogels swell rapidly to be too large to pass through the stomach - large floating system
how do gastroretentive systems work
retained within the stomach for an extended period of time
advantages of gastroretentive systems
useful for drugs with narrow absorption window in the intestine, good for local action
disadvantages of gastroretentive systems
some controversy over safety and efficacy - bioadhesive
why use colon targeting drugs
for local treatment, systemic protein absorption and chronopharmacology
chronopharmacology
creates delays in the times that medications are taken
rectal delivery
for more distal regions of colon, <50ml will stay in the rectum - usually pH controlled system
colonic bacterial azoreduction delivery
5-aminosalicylic linked via azo bridge, cleaved by colonic bacteria so the drug can exert its therapeutic effect
colonic bacterial polysaccharides delivery
using polysaccharides that are only degraded in the colon in dosage forms
timed release systems delivery
insoluble capsule sealed with hydrogel plug that swells and releases drug
