Lecture 9

Question 1

What is salting out?

Answer 1

when you add something which is soluble in one component,
or its solubility is markedly different in the TWO components
This causes the mutual solubility of the liquid pair to decrease

The UCT will increase (e.g. 0.1M napthalene to phenol water)
and LCT will decrease (e.g. 0.1M KCl added to phenol water mixture)

Question 2

What is blending?

Answer 2

where the mutual solubility of the pair is increased by adding an additive which is soluble in water components in the same proportion to the same extent
This cases UCT to decrease (e.g. succinict acid or sodium oleate added to phenol water mixture)
and LCT to increase

Question 3

What happens when you add an additive to any 2 pairs?

Answer 3

it becomes 3 components.

Question 4

how can you determine the solubility on each component?

Answer 4

using a ternary phase diagram

e.g. 1 phase in which all components are all soluble
2 phases in which one of the components is not soluble

Question 5

what factors influence the thermodynamic solubility of a drug?

Answer 5

lattice energy 
cavitation energy
solvation energy
entropy
enthalpy

Question 6

What is lattice energy?

Answer 6

interactions among solute molecules in the crystal

Question 7

what is cavitation energy?

Answer 7

interactions among the solvent molecules in the space required to accomodate the solute

Question 8

what is solvation energy?

Answer 8

stablising interactions between solute and solvent

Question 9

what is entropy?

Answer 9

a measure of randomness or disorder within a system

Question 10

what is enthalpy?

Answer 10

amount of heat absorbed or evolved during the dissolution process

Question 11

What are the steps of solvation?

Answer 11

1) initiall solvent and solute are segregated from each other.
The primary interacts are between other molecules of the same type
2) lattice energy and cavitation energy interactions are broken. Entropy increaases slightly due to disruption of hydrgoen bonds among the solvent molecules. Solute starts to move into solution
3) when solute is surrounded by the solvent, solvation energy interactions are formed. Entropy decreases due to mixing of solute and solvent as well as the new short range order due to the presence of the solute

Question 12

how can energy changes which take place within solute solvent interactions be exlained?

Answer 12

using gibbs energy equation

Question 13

what is free energy?

Answer 13

the energy available for any system to do work

Question 14

What must G be for the process to be spontaneous?

Answer 14

negative

Question 15

What does a -G value mean?

Answer 15

we dont require extra energy to break bonds

Question 16

What is enthalpy?

Answer 16

the amount of heat absorbed or evolved during the dissolution process

Question 17

What is an exothermic reaction?

Answer 17

if heat evolves when molecules of solute are dispersed into the solvent.
Indicated by a negative ΔH value

Question 18

What is an endothermic reaction?

Answer 18

if heat is abosrbed when molecules of ions or solute are separated. Indicated by a positive ΔH balue

Question 19

What is ΔS?

Answer 19

the change in entropy
POSITIVE for any process such as dissolution due to mingling of solute and solvent and the disruption of the ordered network of bonds among solvent molecules

Question 20

What factors affect the solubility of solids?

Answer 20

temperature
molecular structure of solute
nature of solvents
crystal characteristics
acid base properties of drug

Question 21

how does temperature influence the solubility of solids?

Answer 21

a change in temeprature either increases or decreases solubility of a substance depending on the nature of the reaction
if dissolution is endothermic, heat is absorbed naturally so increasing temperature will increase solubility

if dissolution is exothermic, heat is naturally released, so an increased temperature will decrease solubility

Question 22

What is partiuclar about the temperature solubility relationship of sodium sulphate

Answer 22

it has a temperature where solubility increases, and another temperature where it decreases

Question 23

How is solubility phenomena used in first aid?

Answer 23

the cold pack.
there is salt, ammonium nitrate and water, when mixted the endothermic reaction takes place so takes heat from its surroundings

Question 24

how does molecular structure affect solubility of solids?

Answer 24

• structure of solutes affects the solubility of each solvent
• straight compunds are less soluble than branched compounds
• small change in molecular structre can have a marked effect

Question 25

Why is testosterone more soluble?

Answer 25

it has a higher solubility due to the OH functional group

Question 26

an introduction of which functional group can decrease solubility?

Answer 26

methyl group

Question 27

How can molecular structure be changed?

Answer 27

with ionisation

Question 28

What can result from the conversion of a weak acid to its sodium salt?

Answer 28

it can lead to a much greater degree of ionic dissociation of the compound when it dissociates in water e.g. the weak acid is partially soluble due to partial ionisation however the solubility of salicylic acid is practically insoluble

Question 29

how can we use solubility phenomena for other principles?

Answer 29

higher solubility of a drug can result in a bitter taste, we can mask this by adding a palmitate to the compound so you dont get the taste as soon as you take the medicine can reduce excessive degadation of certain drugs in the gut can enhance or reduce the rate of absorption of drugs

Question 30

What is a cosolvent?

Answer 30

a substance added to obtain an aqueous system that contains solute in their excess of their solubility in water e.g. ethanol and propylene glycol

Question 31

What do surfactants have?

Answer 31

both hydrophilc and hydrophobic portions

Question 32

What can surfactants form?

Answer 32

micelles

Question 33

What does solubility of a surfactant depend on?

Answer 33

their HLB value, | High HLB is hydrophilic, low HLB is hydrophobic

Question 34

Why are crystals hard to solubilise?

Answer 34

organised structures like crystals require more energy to break the bonds the change in enthalpy is determined by the strength of interactions between adjacent molecules in crystal lattice amorphous substances are easier to solubilise

Question 35

What are solvates?

Answer 35

the product formed by solvation

Question 36

What are hydrates?

Answer 36

the product formed where water is the solvation molecule

Question 37

Why do hydrated crystals typically exhibit lower solubility in water?

Answer 37

Water can form a H bond between the 2 drug molecules and tie the lattice together creating a mch stronger and stable lattice

Question 38

Which form of drug always as a higher solubility?

Answer 38

the ionised form

Question 39

In the dissolution of acetic acid, what happens in acidic conditions? what happens in basic conditions?

Answer 39

in acidic conditions solubility decreases | in basic conditions solubility increases

Question 40

What can the change in solubility in different pH be determined by?

Answer 40

the pHP equation where pHp is the pH below which an acid precipitates

Question 41

What happens to the solute in a mixture of 2 immiscible solvents?

Answer 41

It will try to distribute between the 2 phases

Question 42

what is partitioning?

Answer 42

how well the drug will distribute between 2 systems

Question 43

How can the partition coefficient be predicted?

Answer 43

using octanol and water. We obtain the ratio of concentration of a substnace in the octanol phase, to its concentration in the aqueous phase at equillibrium at a constant temperature Then we obtain a LogP

Question 44

What does a higher LogP mean?

Answer 44

the solute is more lipophilic i.e. less polar

Question 45

what does a lower LogP mean?

Answer 45

the solute is more hydrophilic i.e. more polar

Question 46

What is partition coefficient useful to?

Answer 46

solubility drug absorption release of drug from dosage forms

Question 47

What is an old but widely used method to determine the parition coefficient?

Answer 47

shake flask method Where the flask with the 2 immiscible liquids is shaken and partition is achieved when the 2 phases are separated. the concentration of the solute in each phase is measured the 2 phases are mutually saturated with each other

Question 48

what are the disadvantages of the shake flask method?

Answer 48

May take 24 hours to achieve it is only limited to compounds with logP of -2 to 4 and sometimes to 5 Co misciblity and subsequent formation of an emulsion between the two phases may occur Used for unionised drugs only