co-solvents Flashcards
what are co-solvents?
A solute (drug) is more soluble in a mixture of solvents than in
one solvent, this is known as “co-solvency” and the solvent
(s) that in combination and increase the solubility of the
solute is called co-solvent (s). This will lead to …
A pharmaceutical solution is simply “a homogeneous,
molecular, clear mixture of a solute dissolved in a solvent.
Water is the most common solvent (due to its safety and
low cost), however organic solvents are used in combination
with water, for a purpose
are all drugs water soluble? what do we do about it?
Not all drugs are soluble in water although they have
pharmacological actions. Accordingly, the pharmaceutical
formulations of poorly water soluble drugs, in the form of
solutions (orally, injection, drops, ..), is challenging.
Therefore, one method to enhance solubility of those drugs is
to add water miscible liquid (Co-solvent) in which drug will
have a higher solubility.
give examples of co-solvents?
glycerol, propylene glycol,
polyethylene glycol and ethanol. The amount of co-solvents
will depend on their toxicity.
what factors need to be considered with co-solvents?
The saturation solubility of the drug in water-co-
solvent (s) mixture, to avoid precipitation of the drug.
The concentration of the drug in the pharmaceutical
solutions to give therapeutic effects
The limit of the co-solvents
is change of the pH of the solution affecting the
solubility of the drug in water/co-solvent systems
what should you do to avoid precipitation ?
The drug distributes via the solvent as molecules or ions, and hence to
avoid drug precipitation and to enhance drug stability, the drug
concentration in a solution should be below its saturation solubility in
this solvent.
what should be done if the drug is soluble in organic solvents which are toxic?
the amount
of the co-solvents should be monitored, i.e. co-solvents must be safe at
the concentration used (the route of drug administration should be taken
into account as well) and compatible
what is the mechanism of action of co-solvents?
Co-solvents are applied to increase the water (a
polar solvent) solubility of non-polar drugs, with
no ionizable groups.
Accordingly, the co-solvent (s) will reduce the
polarity of water and increase drug aqueous
solubility.
Linear increase in co-solvent fraction (mass)
leads to increase in drug solubility (mass fraction)
give an example of co-solvency
Phenobarbital in a mixture of water, alcohol and
glycerol, conclusion: for effective therapeutic drug
action and at the same time stable, safe
formulations, the correct amount of each co-
solvent can be chosen.
what are applications of co-solvency?
Alcohols and polyhydric solvents:
Ethanol –most commonly used in different
pharmaceutical solutions: oral (Elixirs), topical,
parenteral.
how do you determine saturated drug solubility in water/ co-solvent mixtures?
Shake flask method for drug suspensions in different
mixtures at different temperatures.
➢Different proportions of water : co-solvents to be
used
➢Equilibrium
➢Repeat experiments
➢Filtration of the suspension and determination of the
drug soluble fraction in the supernatants using the
suitable analytical method
➢Stability of the drug should be taken into accounts
what is the importance of pharmaceutical solutions and co-solvents?
Rapid action
➢ Drug is in a molecular form, hence it is ready for
absorption
➢ Dose uniformity
➢Patient compliance, for elderly and children
what is the difference between preferntial binding and hydrating?
in binding the additive surrounds the protein
in hydration it is more dispersed
define preferential hydration
xclusion of the cosolvent from the protein surface due to steric effects or charge effects. More water molecules Are around the protein Fully hydrated and stabilised it is thermodynamic, causes increase in free energy
what is preferential binding?
nonspecifically
or binding to specific sites on protein surface.
if bind to active site inactivate enzymes for
example
how do cyclodextrins differ?
by the number of glucose uniys
diameter of the hole
solubility in water a t 25 degrese
