Lecture 19 - Drug solubility and dissolution 4

Question 1

A type of inclusion compounds are called…

Answer 1

cyclodextrins

Question 2

What is the role of inclusion compounds?

Answer 2

increase solubility of poorly soluble hydrophobic drug molecules

Question 3

How do inclusion cyclodextrins form?

Answer 3

They are enzymatically modified starches- in other words, enzymes play a key role in the synthesis of cyclodextrin molecules.

Question 4

Describe the structure of cyclodextrin molecules.

Answer 4

• 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.

Question 5

Name the three types of cyclodextrins, state how many units they are made up of and rank them in order of solubility

Answer 5

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

Question 6

How do inclusion complexes form, cyclodextrin- host complexes?

Answer 6

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.

Question 7

What is the host-guest ration in a cyclodextrin complex?

Answer 7

1:1

Question 8

explain this

Answer 8

Eventually, the inclusion complexes break down and the hydrophobic drug molecules leave the CDs and the CDs and guest hydrophobic molecules recrystallize separately

Question 9

What is another name for surface active agents

Answer 9

surfactants

Question 10

What is surface activity?

Answer 10

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

Question 11

What is surface tension?

Answer 11

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.

Question 12

How do amphiphilic molecules reduce surface tension?

Answer 12

• 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.

Question 13

A surfactant is…

Answer 13

a chemical compound which reduce the surface tension between two liquids, liquid and gas, or liquid and a solid

Question 14

Surfactants and amphiphiles. Describe their structure

Answer 14

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.

Question 15

What characteristic would make a surfactant more effective?

Answer 15

The surfactants are better if the polar head is much more hydrophilic than the tail- bigger difference in polarity between the head and tail.

Question 16

The hydrophilic head of a surfactant may be….

Answer 16

non-ionic or ionic

Question 17

The balance between the two regions of the surfactant determines…

Answer 17

… the surfactant solubility in water and oil, its applications, its place on the HLB- hydrophile-lipophile balance scale.

Question 18

Give properties of the polar region of the surfactants which have to be present.

Answer 18

• 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.

Question 19

How do we classify surfactants? list the classes.

Answer 19

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

Question 20

How do surfactants act in dilute solutions/ at low concentrations?

Answer 20

• 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.

Question 21

In dilute solutions, we say that the size of surfactants is ‘sub-colloidal’. What does this term mean?

Answer 21

referrs to the size of a surfactant/amphiphile when they are present in low concentration in a liquid medium

Question 22

In concentrated solutions of surfactants…

Answer 22

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.

Question 23

micelles lie within a size range named…

Answer 23

colloidal. These particles are larger than molecules but are small enough to remain suspended in a mixture

Question 24

What is critical micelle concentration, CMC?

Answer 24

the concentration of monomer- the surfactants - at which micelles form.

Question 25

What is the aggregation number?

Answer 25

The number of monomers that aggregate to form aggregates/micelles

Question 26

Micellization is an alternative mechanism to adsorption. What is adsorption?

Answer 26

Adsorption = the adhesion of chemical species present in a gas or liquid phase onto/near the outer surface of a solid adsorbent.

Question 27

What is the hydrophobic effect?

Answer 27

• 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.

Question 28

At CMC, what changes are there to the properties of surfactants?

Answer 28

osmotic pressure, turbidity, electrical conductance, surface tension.

Question 29

What can increase CMC?

Answer 29

increase in polarity of the head group

Question 30

What can decrease CMC?

Answer 30

decrease with temperature, pH (surfactants are weak electrolytes), a second surfactant, addition of electrolytes and organic matter.

Question 31

Define Kraft point.

Answer 31

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

Question 32

How is kraft point visually determined?

Answer 32

solution is fully clarified

Question 33

What is cloud point?

Answer 33

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

Question 34

What is critical micelle pH?

Answer 34

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.

Question 35

At high concentrations of surfactants, the geometric properties of micelles change- their shapes change. Give the different shapes

Answer 35

• Cylindrical rods and flattened discs
• Liquid crystals – hexagonal, middle phase
• Lamellar phase
• Bilayers
• vesicles