L19 - drug sol & dissolution rate 4 Flashcards
class 1 drug
- high solubility
- high permeability
e.g simple oral dosage form
class 2 drug
- low solubility
- high permeability
class 3 drug
- high solubility
- low permeability
class 4 drug
- low solubility
- low permeability
how do cyclodextrins work?
- inclusion compounds
- bring molecule into solution
- made by putting non-polar part of one molecule into non-polar cavity of a water-soluble molecule
describe the structure of cyclodextrins (CD)
- enzymatically modified starches so less toxic
- cylindrical ring
- hydrophilic outer surface
- cavity is lipophillic/ non-polar
- glucopyranose units forms ring of 6 units, b-CD units, g-CD 8 units
what is the host guest ratio of CD usually?
1:1 so lipophilic molecules can be wholly or partially accommodated for in a complex
dissolution- dissociation- recrystallise process of CD complex of a poorly soluble guest
- crystalline complex is soluble in water
- outer shell is dissolved
- so CD can leave complex
- this is an easy way to increase solubility of drug in short time that is not otherwise soluble in water
how has β-cyclodextrin been used to improve the solubility of ibuprofen?
- mixture of ibuprofen and CD produces complex in water bath (dissolution medium)
- dissolution tests show an increase in dissolution rate of ibuprofen
- comparing dissolution profiles has show that at a low pH there is a bigger effect of the complex on the release of ibuprofen (low solubility in water)
adverse effects of CD
β-cyclodextrins have found a way to be used as controlled release of drug
what are surfactants?
surface active agents
what could the ability to reduce surface tension at an interface without needing large concentrations do?
blur the difference between solvent and solute
what are most marked events obtained with?
solutes that combine in their molecule structure
- one element has a high affinity for solvent
- one doesn’t
e.g phospholipid
what does the balance between hydrophilic part and hydrophobic part of molecule determine?
- surfactant solubility in water and oil
- surfactant applications
- place on scales of hydrophile-lipophile balance (HBL)
describe the polar region
- high affinity for water
- can pull long hydrocarbon chains into water
- must be polar enough to hold non-polar region in solution
4 classifications of surfactants
- anionic
- cationic
- non ionic
- zwitterionic
properties of surfactants at dilute solutions
- surfactants act as normal solutions and electrolytes
- the amphiphiles exist separately
- size of amphiphiles causes them to be sub-colloidal
define subcolloidal
solution is mixture of 2 substances where insoluble particles of one substance are suspended throughout the other substance on a microscopic scale
properties of surfactant solutions at concentrated solutions
- surfactants aggregate/ come together over narrow concentration range
- aggregates = micelles
Critical micelle concentration (CMC)
conc of monomer at which micelles form
aggregation number of micelles
number of monomers that aggregate to form a micelle
micellisation
- alt mechanism to adsorption (molecules stick to surface)
- allows strong water water interactions that would not happen if surfactant molecules were in solution as single molecules between water molecules (hydrophobic effect)
what happens as you increase surfactant?
they arrange so head faces water and tails face away
what happens if you increase conc of surfactant even more?
they self aggregate
at CMC what are the changes in physical properties of surfactants?
- osmotic pressure
- turbidity
- electrical conductance
- surface tension
as you add surfactant what happens to osmotic pressure?
increases, then CMC is achieved so it stabilises
as you add surfactant what happens to turbidity?
a small increase, but after cmc is achieved there is a huge increase
as you add surfactant what happens to surface tension?
decreases, then once cmc is achieved (once micelle formation is achieved) it stabilises
as you add surfactant what happens to molar conductivity?
decreases, then cmc is achieved and it decreases even more
factors affecting cmc (micelle formation) IMPORTANT
- CMC increases as polarity of head increases
- CMC decreases with:
- temperature (cloud point)
- pH (remember surfactants are weak electrolytes)
- second surfactant
- addition of electrolytes and organic matter
effect of carbon chain on length of CMC?
as carbon chain increases (tail) but polar head stays same, CMC will DECREASE.
as at longer chain length the system becomes more unstable thermodynamically.
critical values for micelles
- CMC
- Kraft point (critical micelle temp)
- cloud point
- critical micelle pH
the Kraft point
temp at which solubility becomes equal to cmc
at a temperature below the Kraft point describe cmc and solubility
cmc will be bigger than solubility and micelles will not be able to form
when the temperature is above the Kraft point explain what happens
surfactant forms micelles, self-solubilisation
unassociated surfactant has ?
limited solubility
micelles are?
highly soluble and can acclimate a large amount of surfactant
cloud point
- non ionic surfactants
- increase in temp causes
1. dehydration of cahains
2. decrease in water sol
3. formation of large micelles
so solution becomes cloudy
reversible process for cloud point
- cooling
- formation of small micelle and clarification
critical micelle pH
- if ionised form of compound is surface active
- and unionised form is inactive
- or has lower cmc than ionised form
- than pH can induce micellisation
