L19 - Drug Solubility And Dissolution Rate 4 Flashcards
What do inclusion compounds result from?
incorporation of non-polar portion into non-polar cavity of another molecule that is water soluble
What are cyclidextrins?
Ezymatically modified starches
What do CDs glucopyranose units form? (3)
A ring
- a-CD ring of 6 units
- b-CD ring of 7 units
- g-CD ring of 8 units
Why is the cyclodextrin ring cylindrical? (2)
- outer surface is hydrophilic
- internal surface of cavity is non-polar
What ratio are liphophilic molecules in with their host?
1:1
How are crystalline complexes of the inclusion complexes formed?
- dissolved CD and hydrophobic poorly soluble drug combine
= form inclusion complex - Non polar in hostile environment
= forms crystalline complex
How does the dissolution-dissociation-recrystallisation process of a CD complex of a poorly soluble guest happen? (3)
- crystalline complex dissolves
- CD recrystalises
- guest separates
What has the B-cyclodextrin to improve the solubility of ibuprofen shown at lower pH? (2)
- fast and complete release of the drug in 30 min
- when compared to the long time release observed with the mixtures of ibuprofen without CD
What are some examples of disadvantages of CDs? (3)
- di-O-methyl B-CD has a strong affinity for cholesterol and is a haemolytic
- 2-hydroxypropyl B-CD increases solubility of progesterone
- B-cyclodextrins find a way to be used as controlled release of drugs
What does a surface avtive solute have the ability to do?
Reduce the surface tension at an interface
- w/o requireing large concs
What could large concs of an active solute do?
Blur the distinction between solvent and solute
= the lower the conc require, the better surface-activity properties of a solute
What structure do you need for active solutes? (2)
- one element having a high affinity for the solvent
- one element having a minimal affinity for the solvent
What is a surfactant?
Surface active agent
What is the structure of a surfactant composed of? (2)
- hydrophilic/polar head group (nonionic, ionic)
- lipophilic/non polar chain
What does the balance of the two regions in a surfactant determine? (3)
- surfactant solubility in water and oil
- its applications
- place on the scale of Hydrophile-Lipophile Balance (HLB)
What should a polar region have? (3)
- affinity for water
- able to pull long hydrocarbon chains into water
- sufficiently polar to hold the nonpolar region of the surfactant in solution
What are the charges carried by the polar part? (4)
- anionic
- cationic
- nonionic
- zwitterionic
What do surfactants solution act like at dilute solutions? (2)
- normal solutes (normal electrolytes)
- amphiphiles exist separately, such size as sub-colloidal
What do surfactants solutions act like at concentrated solutions? (2)
- aggregate over narrow conc ranges = micelles
- size range as colloidal 50A
What is the critical miceele concentration (CMC)?
The concentration of monomer at which micelles form
What is the aggreagtion number?
The number of monomers that aggregate to form a micelle
What is micellisation?
alternative mechanism to adsorption
What does micellisation permit?
Strong water-water interactions
What is the hydrophobic effect?
Prevention of water-water interactions if the surfactant molecule were in solution as single molecules between water molecules
What happens as the concentration of surfactants increases? (2)
- adsorb to surface
- form micelles at CMC
What surfactant physical properties can change at CMC? (4)
- osmotic pressure
- turbidity
- electrical conductance
- surface tension
What happens to the physical properties of surfactants at CMC? (4)
- Osmotic pressure - slower linear increase
- Turbidity - increases
- Surface tension - remain constant
- Molar conductivity - decreases
This behaviour is explained by the formation of micelles or aggregates of the surfactant molecules in which: (2)
- lipophilic chains are orientated towards interior of micelle
- hydrophilic groups are in contact with the aq mediun
When may CMC increase with?
Increase in polarity of head group
When may CMC decrease with? (4)
- temperature (cloud point)
- pH (surfactants are weak electrolytes)
- second surfactant
- addition of electrolytes and organic matter
What are the critical values for micelles? (4)
- CMC
- Kraft point
- cloud point
- critical micelle pH
What is the kraft point?
T at which the solubility = CMC
What happens when T < kraft point?
CMC > solubility
- micelles cannot form
What happens when T > kraft point?
Surfactant form micelles
- self-solubilisation
What do unassociated surfactants have compared to micelles?
Limited solubility
- micelles are highly soluble, can accomodate large amount of surfactants
What is the cloud point? (3)
Increase in temp causes:
- dehydration of POE chains
- decreased water solubility
- formation of large micelles = cloudy solution
How to reverse the cloud point? (2)
- cooling
- formation of small micelles = clarification
What are POE chains?
Polyethylene oxide
H-[OCH2CH2]n-OH
- increase polarity of non-ionic surfactants
What is the critical micelle pH?
If ionised form of a compound is surface active and unionised form is surface inactive, then a change in pH can induce micellisation
What are the geometric properties of micelles? (5)
At high con of surfactants, higher visosity systems may occur:
- cylindrical rods, flattenes disks
- liquid crystal (hexagonal phase, middle phase)
- lamellar phase (neat phase)
- bilayers
- vesicles
