co-solvents

Question 1

What are co-solvents?

Answer 1

solute (drug) is more soluble in a mixture of solvents than in 1 solvent - ‘‘co-solvency’’
the solvent that increaes the solubility of the solute is called the co-colvent

Question 2

What is a solution?

Answer 2

a homogenous, molecular, clear mixture of a solute dissolved in a solvent

Question 3

What is the most common solvent?

Answer 3

water

- safety and low cost

Question 4

What other things are used as solvents?

Answer 4

organic solvents

Question 5

Why are organic solvents used?

Answer 5

not all drugs are soluble in water

Question 6

How to enhance solubility of water insoluble drugs?

Answer 6

add water miscible liquid (co-solvent) which the drug will have a higher solubility
- organic solvent

Question 7

What does an organic solvent need to be?

Answer 7

safe

miscible with water (water is most of the solution)

Question 8

examples for co-solvents

Answer 8

glycerol
propylele glycol
polyethylele glycol
ethanol

Question 9

What does the amount of co-solvent depend on?

Answer 9

their toxicity

Question 10

factors to be considered

Answer 10

1. SATURATION SOLUBILITY of the drug in water co-solvent mixture to avoid precipitation of the drug
2. CONCENTRATION of the drug in the pharmaceutical solutions to give therapeutic effects
3. LIMIT of the co-colvents
4. does change in pH of the solution affect the solubility of the drug in water/co-solvent system?

Question 11

example of a small drug molecule

Answer 11

paracetamol

Question 12

example of macromolecule drugs

Answer 12

insulin

growth factor

Question 13

Why should the conc of drug in solution be below its saturation solubility in the solvent?

Answer 13

to avoid drug precipitation and to enhance drug stability

Question 14

How does the drug distribute via the solvent?

Answer 14

as molecules or ions

Question 15

Can more than 1 co-solvent be used?

Answer 15

yes

Question 16

Why are co-solvents used?

Answer 16

to increase the water (polar solvent) solubility of non-polar drugs with no ionisable groups

Question 17

How do co-solvents work?

Answer 17

reduce the polarity of water and increase drug aqueous solubility

Question 18

What increases drug solubility?

Answer 18

linear increase in co-solvent fraction leads to increase in drug solubility
-> inc co-solvent inc solubility of drug

Question 19

mesurement for solubility (y axis)

Answer 19

% w/v

Question 20

most common alcohol used as a co-solvent

Answer 20

ethanol

Question 21

examples where ethanol is used as a co-solvent

Answer 21

orals (Elixirs)
topical
parenteral

Question 22

structure of ethanol

Answer 22

CH3-CH2-OH

Question 23

When is propylene glycol used?

Answer 23

oral
topical
parenteral
ear

Question 24

structure of propylene glycol

Answer 24

CH3CH(OH)CH2OH

Question 25

When is polyethylene glycol used?

Answer 25

parenteral solutions

Question 26

When is glycerol used as a co-colvent?

Answer 26

oral | parenteral

Question 27

structure of glycerol

Answer 27

C3 H8 O3

Question 28

How to determine saturated drug solubility in water/co=solvent mixtures?

Answer 28

shake flask method for the drug suspension in different mixtures at different temperatures different proportions of water:co-colvent used -> until you see drug precipitate (super saturation) shake until they reach equilibrium (about 48hrs0 repeat experiment at least 3 times filtration of the suspension and determine the drug soluble fraction in the supernatant

Question 29

Why are co-solvents important for pharmacsutical solutions?

Answer 29

- rapid action - drug is in a molecular form, ready for absorption - dose uniformity (diff to suspension, need to shake) - patient compliance (elderly/children)

Question 30

What is preferential HYDRATION of a protein?

Answer 30

- exclusion of the co-solvent from the protein surface due to steric effects/charge effects - more water molecules around the protein - protein is fully hydrated and stabilised - thermodynamic, increases free energy

Question 31

What is preferential BINDING to a protein?

Answer 31

- cosolvent binding to protein surface - non-specifically or binding to specific sites on the protein surface - if it binds to active site it will inactivate enzymes - > cosolvent not working properly

Question 32

How many glucose units in cyclodextrins (alpha, beta, gamma) - how does this compare to the diameter of the hole - solubility of each

Answer 32

alpha - 6 glucose units - diameter = 0.5 nm - solubility = 14.2 beta - 7 glucose - 0.6 nm - 1.85 gamma - 8 glucose - 0.8 nm - 23.2

Question 33

structure of cyclodextrins

Answer 33

- polar outer surface (dissolves in water) - less polar inner cavity - > hydrophobic drug molecules can fit inside, will still be hydrophilic on outside

Question 34

benefits of using cyclodextrins

Answer 34

- inc bioavailability of hydrophobic drugs - enhanced of absorption of hydrophobic and hydrophilic drugs - lack of toxicity - inc stability of peptide hormones - can include volatile oils - onversion of liquid drugs to solid powders - masks taste - prevent drug-excipient interactions

Question 35

What is a saturated solution?

Answer 35

when equilibrium is present between un-dissolved and dissolved solute

Question 36

What is solubility?

Answer 36

the amount of solute that passes into solution to start the equilibrium at constant temperature and pressure to produce the solution

Question 37

What happens with a supersaturated solution?

Answer 37

excess solute will precipitate - > can't dissolve any more drug in the solution - > drug will precipitate, can see it

Question 38

units for solubility

Answer 38

weight/volume - kg/m cubed (SI units) 1g/L % w/v % w/w mole fraction

Question 39

What is mole fraction?

Answer 39

no of moles of solute (n1, drug) / total no of moles of solute and solvent (n2) n1 / (n1 + n2)

Question 40

What does very soluble mean?

Answer 40

< 1g of solvent is needed to dissolve 1g of solute

Question 41

What does freely soluble mean?

Answer 41

1-10g of solvent needed to dissolve 1g of solute

Question 42

non-polar solutes in a polar solventts?

Answer 42

will not dissolve - no force of attraction/weak force - solutes will not disperse - > solute precipitates

Question 43

How to overcome attraction between solute molecules? (when they don't attract)

Answer 43

co-solvency

Question 44

solute + co-solvent

Answer 44

= solution

Question 45

factors affecting solubility of solids in liquids

Answer 45

- nature of solvents - solute characteristics (crystals, particle size) - excipients (solubilising agents)

Question 46

What scale of polarity is used for a solute?

Answer 46

oil:water partition coefficient | K o/w

Question 47

formula for logP

Answer 47

log K o/w = log P

Question 48

What is the logP for lipophilic drugs (un-ionisable)?

Answer 48

logP > 1

Question 49

What solvents do lipophilic drugs that are un-ionisable use?

Answer 49

can't use non-aqueous solvents esp for injections (logP >1)

Question 50

conentration of ethanol used as a co-solvent | - why can't more than this be used?

Answer 50

10% | - over this will cause haemolysis, pain

Question 51

What other thing needs to included in injection formulations as well as co-solvent?

Answer 51

isotonic salts

Question 52

What should the dielectric constant be for water miscible solvent?

Answer 52

dielectric constant between 25 and 80

Question 53

dielectric contant of water

Answer 53

80 (safe)

Question 54

What solvent cannot be used in pharmaceutical preparations?

Answer 54

methanol - > toxic - > can be used for separation and extraction

Question 55

examples of co-solvents

Answer 55

``` water ethanol propylene glycol glycerol PEG 300/400 ```