Lecture 18 - Drug solubility and dissolution rate 3

Question 1

Salt forms modify the pH of……… …………. . Explain.

Answer 1

diffusion layer

Salt of a weak acid increases the pH of the diffusion layer. Salt of a weak base will decrease the pH of the diffusion layer

Question 2

The pH of the diffusion layer is the same as the bulk solution if….

Answer 2

we use a free acid

Question 3

The pH of the diffusion layer is the same as the salt if…

Answer 3

we use salt form of the drug.

Question 4

The use of salt form results in a controlled pH of the diffusion layer, regardless of…

Answer 4

• the position in the GI tract

Question 5

Two positives of salts modifying pH of diffusion layer

Answer 5

• improves dissolution rate
• good for when developing slow-release/modified release products.

Question 6

Salts cannot always be used to modify solubility of drugs- compounds are not always weak acids/bases. The drug may be a ……….. ………….. compound.

Answer 6

non polar compound.

Question 7

Non polar compounds are usually lipophilic. What is the property of a lipophilic compound?

Answer 7

cannot dissolve in water.

Question 8

We cannot decrease lipophilicity of non-polar drug molecules. But we can….

Answer 8

decrease polarity of the solvent, which allows the non-polar compound to dissolve better.

Question 9

define cosolvent.

Answer 9

The solvents that in combination increase the solubility of the solute

Question 10

Define co-solvency

Answer 10

frequently a solute is more soluble in a mixture of solvents than in one alone- this is co-solvency.

Question 11

The purpose of cosolvency… (three things)

Answer 11

to create aqueous based systems in which the drug solubility is higher than its aqueous solubility.
- to formulate higher concentrations of the drug
- to improve the stability of the formulation.

Question 12

Give some properties of cosolvents.

Answer 12

• Organic compounds
• Miscible with water
• Better solvents for the drug than water
• Contain hydrogen bond donor and acceptor groups and have small hydrocarbon regions.

Question 13

Most cosolvents are liquids- name three

Answer 13

glycerol, propylene glycol

Question 14

cosolvents can be solids. What must they be?

Answer 14

highly soluble in water.

Question 15

How do cosolvents work to increase solubility of non-polar drug?

Answer 15

• Decrease the hydrogen bond density of the aqueous system
• Reduce the cohesion of water/ cohesive interactions of water (interactions between molecules of the same type)
• Reduce polarity of the solution- reduce the surface tension, dielectric constant (a measure of the polar nature of the solvent, liquids with high dielectric constants can reduce the attractive forces between oppositely charged ions formed when a salt/electrolyte dissociates. Water has a high dielectric constant) and solubility parameter.
• The makes the solution less effective than water at squeezing out non-polar solutes.

Question 16

The increase in cosolvent concentration increases…

Answer 16

solubility

Question 17

Describe how to graphically show the solubility by co-solvency- draw one. How do we find the solubilization slope and what does it tell us?

Answer 17

• Plot cosolvent concentration against log solute concentration. As the cosolvent concentration increases the log solute concentration increases.
• The slope/gradient gives you sigma- the solubilization slope, which is the effectiveness of a cosolvent as a solubilizer for a particular solute.

Question 18

What can solubilization slopes be used for?

Answer 18

We can compare the slopes of different co-solvents to see how effective they are

Question 19

The addition of a cosolvent will increase the solubility of a nonpolar and semipolar solute in water. But, what happens when the the solute becomes more polar? Describe desolubilization.

Answer 19

• As the solute becomes more polar, co-solvency becomes less efficient. The co-solvents will decrease the solubility of polar solute in water.

Question 20

Explain this table in terms of DE solubilization.

Answer 20

Histidine is more polar than indomethacin- smaller logP. But, the solubilization slope is negative because cosolvency is less efficient- it reduces histidine’s ability to dissolve in water