L18 - drug sol & dissolution rate 3

Question 1

class 2 drug

Answer 1

-low solubility, high permeability
- need to increase SA
- uses surfactants and solvents

Question 1

class 1 drug oral dosage form approach

Answer 1

• high permeability and solubility
• simple solid oral dosage form

Question 2

class 3 drugs

Answer 2

• low permeability, high solubility
• permeability enhancers

Question 3

class 4 drugs

Answer 3

• low permeability and solubility
• increase SA
• solutions using solvents and suspensions
• permeability enhancers

Question 4

dissolution rate of weak base in gi

Answer 4

high dissolution rate in stomach, but as pH of gi tract increases the dissolution rate decreases

Question 5

dissolution rate of weak acid in gi

Answer 5

low dissolution rate in stomach but as you go down gut the rate increases as pH increases

Question 6

salt & pH of diffusion layer

Answer 6

• use of salt form of a drug changes pH of diffusion layer
• salt of a weak acid increases the pH of the diffusion layer
• salt of a weak base decreases pH of diffusion layer

Question 7

what happens if you dissolve NaA (salt of weak acid and strong base) in the gi fluid?

Answer 7

• a basic solution forms
• pH of diffusion layer becomes around 5 or 6
• pH of gastric fluid is 1-3
• so you get fine precipitation of unionised acid HA of drug
• if these fine particles are dissolved rapidly then there is good bioavailability

Question 8

so in conclusion what does the use of salt form lead to?

Answer 8

controlled pH of diffusion layer independently of the position of the gi tract, improving dissolution rate, good for developing slow/controlled release products

Question 9

what is cosolvency?

Answer 9

weak electrolytes act like strong electrolytes or like non electrolytes in solution

Question 10

when does cosolvency happen?

Answer 10

• when drug is ionised at a given pH of solution, so it acts like solution of strong electrolyte
• when pH of solution is changed to a value that will produce the most unionised molecules causing precipitation
• when the solubility of weak electrolytes/ non polar compounds in water is improved by adding water miscible solvent where the compound is soluble
• vehicles used in combination with water to increase solubility of a drug = cosolvents

Question 11

how do vehicles used in combination with water (co solvents) increase solubility?

Answer 11

solubility in these mixed system is greater than that of individual solvents (if you mix alcohol with water, you decrease waters polarity)

Question 12

cosolvency

Answer 12

solute is more soluble in a mixture of solvents than in one

Question 13

cosolvent

Answer 13

solvents, that in combination, increase solubility of solute

Question 14

purposes of cosolvency

Answer 14

1. to get aq system where drug sol is higher than aq solubility
2. formulate higher concs of the drug
3. improve stability of the formulation

Question 15

example of cosolvent

Answer 15

1. organic compounds (usually non polar)
2. miscible with water
3. better solvents than water than drugs (h bond acceptor and donor groups, small hydrocarbon regions)

Question 16

what do cosolvents do to the hydrogen bond density of aq systems?

Answer 16

• decrease it
• so reduce the cohesive interactions of water
• reduce polarity
• solution less effective than water in squeezing out non polar solutes

Question 17

what does the solubilisation slope increase with?

Answer 17

decreasing the polarity of solvent

Question 18

cosolvents + desolubilisation

Answer 18

• adding cosolvent increases solubility of non polar and semi polar solute in water
• as the solute becomes more polar, cosolvency becomes left efficient
• it will decrease solubility of a polar solute in water

Question 19

high logp on solubilisation slope =

Answer 19

high solubilisation slope when mixed with ethanol and water