oral pharmaceutics workshop Flashcards
oral lipophilic drugs premature by which method?
transcellular route
what does Ficks law state?
diffusion is proportional to conc of drug
when is class 3 BCS eligible for biowaiver?
if very rapidly dissolving
when is class 2 BCS eligible for biowaiver?
if weak acids are highly soluble at pH 6.8, plus dissolution
when are oral drugs defined as being soluble in BCS?
when the largest dose of drug is soluble in less than 250ml of water of pH range 1-7.5
when are oral drugs defined as being permeable in BCS?
when more than 90% of the dose given, is absorbed
Why are 40% of NCE poorly soluble?
as discovered through high throughput screening rather than traditional in vitro methods and theres poor
what are the issues with poor drug solubility IN VIVO?
- decreased bioavailability
- increased food effects
- increased effect in diseased states esp GIT
- more frequent incomplete release
- higher inter patient variability
what are the issues with poor drug solubility in formulation?
- severely limited choice on technologies
- increasingly complex dissolution testing
- limited/poor correlation with in vivo
how can you enhance solubility of a class 2 BCS?
salts surfactants nanoparticles self emulsifying systems (particle size reduction solid dispersions cyclodextrin)
how can you enhance permeability of a class 3 BCS?
self emulsifying systems
(absorption enhancing excipients
efflux transport inhibitors)
how can you enhance solubility of a class 4 BCS?
salts surfactants nanoparticles self emulsifying systems (pro drugs co-solvents lyophilisation)
how do co-solvents help solubility?
prevent precipitation
how can you reduce particle size? (to microns e.g.)
- recrystallisation - by adding solvents and anti-solvents
2. conventional comminution and spray drying - mechanical stress
how does reducing particle size enhance solubility?
larger SA
reduced diffusion thickness
increases saturation solubility
