Lecture 19 - Drug solubility and dissolution 4 Flashcards
A type of inclusion compounds are called…
cyclodextrins
What is the role of inclusion compounds?
increase solubility of poorly soluble hydrophobic drug molecules
How do inclusion cyclodextrins form?
They are enzymatically modified starches- in other words, enzymes play a key role in the synthesis of cyclodextrin molecules.
Describe the structure of cyclodextrin molecules.
- they are made up of glucose molecules - D glucopyranose units.
- These are arranged into a ring like structure
- the rings are cyclindrical
- the outer surface of these rings are hydrophilic and the internal cavity is nonpolar.
- The hydrophobic cavity provides a suitable microenvironment for our appropriately sized non polar guest molecule.
Name the three types of cyclodextrins, state how many units they are made up of and rank them in order of solubility
least soluble
- Alpha CDs = ring made of 6 units
- Beta CDs = ring made of 7 units
- Gamma CDs = ring made of 8 units
Most soluble
How do inclusion complexes form, cyclodextrin- host complexes?
Result from the incorporation of a nonpolar region of one molecule into the non-polar cavity of another molecule that is water soluble, allowing the hydrophobic drug molecule to dissolve
They accommodate lipophilic molecules within their structure – appropriately sized lipophilic molecules can be accommodated wholly or partially in the complex.
What is the host-guest ration in a cyclodextrin complex?
1:1
explain this
Eventually, the inclusion complexes break down and the hydrophobic drug molecules leave the CDs and the CDs and guest hydrophobic molecules recrystallize separately
What is another name for surface active agents
surfactants
What is surface activity?
the ability to reduce the surface tension at an interface without requiring large concentrations- large concentrations which could blur the distinction between solvent and solute
What is surface tension?
molecules at the surface of a liquid are not completely surrounded by other molecules. As a result, there is a net inward force of attraction exerted on molecules at the surface from the molecules in the bulk solution, resulting in a tendency for the surface to contract. The contraction of the surface is spontaneous.
How do amphiphilic molecules reduce surface tension?
- Amphiphilic molecules in aqueous solution have a tendency to seek out the surface and orientate themselves in such a way to remove the hydrophobic group from the aqueous environment. The intrusion of surfactant molecules into the surface means that some water molecules are replaced by non-polar groups. There is less IM force between water molecules and non-polar groups than between two water molecules. Therefore, surface tension is reduced.
A surfactant is…
a chemical compound which reduce the surface tension between two liquids, liquid and gas, or liquid and a solid
Surfactants and amphiphiles. Describe their structure
Surfactants must have a highly polar head and a tail which is highly non-polar – an aliphatic hydrocarbon chain. The polar head has a high affinity for the solvent and the tail has minimal affinity for the solvent.
What characteristic would make a surfactant more effective?
The surfactants are better if the polar head is much more hydrophilic than the tail- bigger difference in polarity between the head and tail.
The hydrophilic head of a surfactant may be….
non-ionic or ionic
The balance between the two regions of the surfactant determines…
… the surfactant solubility in water and oil, its applications, its place on the HLB- hydrophile-lipophile balance scale.
Give properties of the polar region of the surfactants which have to be present.
- affinity for water
- capable of pulling long hydrocarbon chains into the water
- the polar group must be sufficiently polar to hold the nonpolar region of the surfactant in solution.
How do we classify surfactants? list the classes.
we classify them based on the nature of their hydrophilic group
- anionic - polar head is negatively charged so counterion is positive
- cationic - polar head is positively charged so the counterion is negative
- non ionic
- zwitterionic – possess polar heads which may be ionised to have both positive and negative charges
How do surfactants act in dilute solutions/ at low concentrations?
- In dilute solutions of surfactants, they act as normal solutes. The amphiphiles (name given to molecules with polar and non-polar end) exist alone in the solution- the molecules are separate, spread out. They do however accumulate at the air/liquid interface, saturating the interface and lowering the surface tension.
In dilute solutions, we say that the size of surfactants is ‘sub-colloidal’. What does this term mean?
referrs to the size of a surfactant/amphiphile when they are present in low concentration in a liquid medium
In concentrated solutions of surfactants…
surfactants (the amphiphiles) aggregate.
Excess surfactant molecules have to move away from the air/liquid interface and into the bulk of solution
The individual surfactant molecules come together/aggregate. The aggregates (group of the amphiphiles) contain 50 or more amphiphiles. We call these aggregates micelles.
micelles lie within a size range named…
colloidal. These particles are larger than molecules but are small enough to remain suspended in a mixture
What is critical micelle concentration, CMC?
the concentration of monomer- the surfactants - at which micelles form.
What is the aggregation number?
The number of monomers that aggregate to form aggregates/micelles
Micellization is an alternative mechanism to adsorption. What is adsorption?
Adsorption = the adhesion of chemical species present in a gas or liquid phase onto/near the outer surface of a solid adsorbent.
What is the hydrophobic effect?
- By forming micelles, water-water interactions are not prevented like they would be if the surfactants were in solution as single molecules- hydrophobic regions face inwards. This is the hydrophobic effect.
At CMC, what changes are there to the properties of surfactants?
osmotic pressure, turbidity, electrical conductance, surface tension.
What can increase CMC?
increase in polarity of the head group
What can decrease CMC?
decrease with temperature, pH (surfactants are weak electrolytes), a second surfactant, addition of electrolytes and organic matter.
Define Kraft point.
critical micelle temperature. The Kraft point= the temperature when solubility becomes equal to CMC. Therefore, above craft point micellization occurs. When T is below the kraft point, the CMC is smaller than solubility and micelles cannot form.
At higher temps, solubility in water increases
How is kraft point visually determined?
solution is fully clarified
What is cloud point?
Kraft points are not really a thing for non-ionic surfactants. Instead, we have cloud points.
If you increase temperature, the polyoxymethylene chains are dehydrated, decreasing water solubility, formation of very large micelles so the solution becomes cloudy. If you cool it down, small micelles form, solution becomes clear- clarification
What is critical micelle pH?
if the ionised form of a compound is surface active- hydrophilic and unionised form is surface inactive, then change in pH can induce micellization. For example, for a weak acid when you increase pH, ionization increases along with CMC and solubility.
At high concentrations of surfactants, the geometric properties of micelles change- their shapes change. Give the different shapes
- Cylindrical rods and flattened discs
- Liquid crystals – hexagonal, middle phase
- Lamellar phase
- Bilayers
- vesicles
