L19 - drug sol & dissolution rate 4

Question 1

class 1 drug

Answer 1

• high solubility
• high permeability
  e.g simple oral dosage form

Question 2

class 2 drug

Answer 2

• low solubility
• high permeability

Question 3

class 3 drug

Answer 3

• high solubility
• low permeability

Question 4

class 4 drug

Answer 4

• low solubility
• low permeability

Question 5

how do cyclodextrins work?

Answer 5

• inclusion compounds
• bring molecule into solution
• made by putting non-polar part of one molecule into non-polar cavity of a water-soluble molecule

Question 6

describe the structure of cyclodextrins (CD)

Answer 6

• enzymatically modified starches so less toxic
• cylindrical ring
• hydrophilic outer surface
• cavity is lipophillic/ non-polar
• glucopyranose units forms ring of 6 units, b-CD units, g-CD 8 units

Question 7

what is the host guest ratio of CD usually?

Answer 7

1:1 so lipophilic molecules can be wholly or partially accommodated for in a complex

Question 8

dissolution- dissociation- recrystallise process of CD complex of a poorly soluble guest

Answer 8

• crystalline complex is soluble in water
• outer shell is dissolved
• so CD can leave complex
• this is an easy way to increase solubility of drug in short time that is not otherwise soluble in water

Question 9

how has β-cyclodextrin been used to improve the solubility of ibuprofen?

Answer 9

• mixture of ibuprofen and CD produces complex in water bath (dissolution medium)
• dissolution tests show an increase in dissolution rate of ibuprofen
• comparing dissolution profiles has show that at a low pH there is a bigger effect of the complex on the release of ibuprofen (low solubility in water)

Question 10

adverse effects of CD

Answer 10

β-cyclodextrins have found a way to be used as controlled release of drug

Question 11

what are surfactants?

Answer 11

surface active agents

Question 12

what could the ability to reduce surface tension at an interface without needing large concentrations do?

Answer 12

blur the difference between solvent and solute

Question 13

what are most marked events obtained with?

Answer 13

solutes that combine in their molecule structure
- one element has a high affinity for solvent
- one doesn’t
e.g phospholipid

Question 14

what does the balance between hydrophilic part and hydrophobic part of molecule determine?

Answer 14

1. surfactant solubility in water and oil
2. surfactant applications
3. place on scales of hydrophile-lipophile balance (HBL)

Question 15

describe the polar region

Answer 15

• high affinity for water
• can pull long hydrocarbon chains into water
• must be polar enough to hold non-polar region in solution

Question 16

4 classifications of surfactants

Answer 16

1. anionic
2. cationic
3. non ionic
4. zwitterionic

Question 17

properties of surfactants at dilute solutions

Answer 17

• surfactants act as normal solutions and electrolytes
• the amphiphiles exist separately
• size of amphiphiles causes them to be sub-colloidal

Question 18

define subcolloidal

Answer 18

solution is mixture of 2 substances where insoluble particles of one substance are suspended throughout the other substance on a microscopic scale

Question 19

properties of surfactant solutions at concentrated solutions

Answer 19

• surfactants aggregate/ come together over narrow concentration range
• aggregates = micelles

Question 20

Critical micelle concentration (CMC)

Answer 20

conc of monomer at which micelles form

Question 21

aggregation number of micelles

Answer 21

number of monomers that aggregate to form a micelle

Question 22

micellisation

Answer 22

• alt mechanism to adsorption (molecules stick to surface)
• allows strong water water interactions that would not happen if surfactant molecules were in solution as single molecules between water molecules (hydrophobic effect)

Question 23

what happens as you increase surfactant?

Answer 23

they arrange so head faces water and tails face away

Question 24

what happens if you increase conc of surfactant even more?

Answer 24

they self aggregate

Question 25

at CMC what are the changes in physical properties of surfactants?

Answer 25

1. osmotic pressure 2. turbidity 3. electrical conductance 4. surface tension

Question 26

as you add surfactant what happens to osmotic pressure?

Answer 26

increases, then CMC is achieved so it stabilises

Question 27

as you add surfactant what happens to turbidity?

Answer 27

a small increase, but after cmc is achieved there is a huge increase

Question 28

as you add surfactant what happens to surface tension?

Answer 28

decreases, then once cmc is achieved (once micelle formation is achieved) it stabilises

Question 29

as you add surfactant what happens to molar conductivity?

Answer 29

decreases, then cmc is achieved and it decreases even more

Question 30

factors affecting cmc (micelle formation) IMPORTANT

Answer 30

1. CMC increases as polarity of head increases 2. CMC decreases with: - temperature (cloud point) - pH (remember surfactants are weak electrolytes) - second surfactant - addition of electrolytes and organic matter

Question 31

effect of carbon chain on length of CMC?

Answer 31

as carbon chain increases (tail) but polar head stays same, CMC will DECREASE. as at longer chain length the system becomes more unstable thermodynamically.

Question 32

critical values for micelles

Answer 32

1. CMC 2. Kraft point (critical micelle temp) 3. cloud point 4. critical micelle pH

Question 33

the Kraft point

Answer 33

temp at which solubility becomes equal to cmc

Question 34

at a temperature below the Kraft point describe cmc and solubility

Answer 34

cmc will be bigger than solubility and micelles will not be able to form

Question 35

when the temperature is above the Kraft point explain what happens

Answer 35

surfactant forms micelles, self-solubilisation

Question 36

unassociated surfactant has ?

Answer 36

limited solubility

Question 37

micelles are?

Answer 37

highly soluble and can acclimate a large amount of surfactant

Question 38

cloud point

Answer 38

- non ionic surfactants - increase in temp causes 1. dehydration of cahains 2. decrease in water sol 3. formation of large micelles so solution becomes cloudy

Question 39

reversible process for cloud point

Answer 39

1. cooling 2. formation of small micelle and clarification

Question 40

critical micelle pH

Answer 40

- if ionised form of compound is surface active - and unionised form is inactive - or has lower cmc than ionised form - than pH can induce micellisation