Lecture 18 - Drug solubility and dissolution rate 3 Flashcards
Salt forms modify the pH of……… …………. . Explain.
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
The pH of the diffusion layer is the same as the bulk solution if….
we use a free acid
The pH of the diffusion layer is the same as the salt if…
we use salt form of the drug.
The use of salt form results in a controlled pH of the diffusion layer, regardless of…
- the position in the GI tract
Two positives of salts modifying pH of diffusion layer
- improves dissolution rate
- good for when developing slow-release/modified release products.
Salts cannot always be used to modify solubility of drugs- compounds are not always weak acids/bases. The drug may be a ……….. ………….. compound.
non polar compound.
Non polar compounds are usually lipophilic. What is the property of a lipophilic compound?
cannot dissolve in water.
We cannot decrease lipophilicity of non-polar drug molecules. But we can….
decrease polarity of the solvent, which allows the non-polar compound to dissolve better.
define cosolvent.
The solvents that in combination increase the solubility of the solute
Define co-solvency
frequently a solute is more soluble in a mixture of solvents than in one alone- this is co-solvency.
The purpose of cosolvency… (three things)
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.
Give some properties of cosolvents.
- Organic compounds
- Miscible with water
- Better solvents for the drug than water
- Contain hydrogen bond donor and acceptor groups and have small hydrocarbon regions.
Most cosolvents are liquids- name three
glycerol, propylene glycol
cosolvents can be solids. What must they be?
highly soluble in water.
How do cosolvents work to increase solubility of non-polar drug?
- 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.
The increase in cosolvent concentration increases…
solubility
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?
- 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.
What can solubilization slopes be used for?
We can compare the slopes of different co-solvents to see how effective they are
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.
- As the solute becomes more polar, co-solvency becomes less efficient. The co-solvents will decrease the solubility of polar solute in water.
Explain this table in terms of DE solubilization.
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
