Lecture 18: drug solubility and dissolution rate 3

what happens to weak bases and weak acids in the stomach?

• a weak base has high dissolution rate in the stomach, dissolution rate falls as u continue down the GI

• a weak acid has minimal dissolution in the stomach but its dissolution rate increases down the gut

what does the salt of a weak acid do to the pH of the diffusion layer

increases

what does the salt of a weak base do to the pH of the diffusion layer

decreases

the pH of the diffusion layer with free acid or salt

free acid: ph of bulk solution

salt: ph of salt

why does increasing the pH of a diffusion layer for a weak acid make it more soluble?

the salt of a weak acid increases the pH of the diffusion layer

• this means that the acid can ionize and therefore is able to solubilise

• this improves dissolution rate

why does decreasing the pH of a diffusion layer for a weak base make it more soluble?

the salt of a weak base decreases the pH of the diffusion layer

• this means that the base can ionize and therefore is able to solubilise

• this improves dissolution rate

what is cosolvency?

when 2 solvents are used in combination to increase the solubility of the solute

what is the purpose cosolvency?

• a system where the drug solubility is higher than the aqueous solubility

• improve stability of formulation

• formulate higher concentrations of the drug

features of cosolvents:

• organic compounds

• miscible with water

• better solvents than water for drugs due to low polarity

some solids are highly soluble in water

all polymers

what does hydrogen bond density give?

the amount of polarity of the solution

how do colsolvents decrease polarity of water?

• they decrease the hydrogen bond density

• reduces cohesive interactions of water

• reduces polarity of the solution

We add cosolvents to water to make the solution less polar in order to increase the solubility of poorly water-soluble (hydrophobic) drugs.

what does reducing polarity do?

decreases:

• surface tension

• dielectric constant

• solubility parameter

what is the formula for solubilisation by cosolvency?

• the solubilisation slope increases with decreasing the polarity of the solvent

as the solute becomes more polar, cosolvency becomes less efficient, will eventually decrease solubility of a polar solute in water