Physicochemical properties Flashcards
Solution
Mixture of 2 or more components that form a homogenous molecular dispersion
Single phase system
Not another phase dispersed in another
Solvent
Component present in greater amounts
Solute
Component present in smaller amounts
Saturated solution
Where the solute is at the limit of its solubility at a given temp. + pressure
Solution = _______ phase
Single
solid solute dissolved into solvent to make it a single phase
Suspension/emulsion = _________ phase
Two
2 types of solution
liquid in liquid
solid in liquid
2 categories in liquid in liquid
Partially miscible
Completely miscible
Example of completely miscible
Ethanol + water
Example of partially miscible
Ether + water
What affects partially miscible
Temperature
2 solutions in solid in liquid
Solution of non-electrolytes (non-ionic)
Solution of electrolytes (form ions in solution)
Examples of solution of non-electrolytes
Organic molecules (sucrose, phenol)
Example of solution of electrolytes
strong electrolytes = NaCl
weak electrolytes = depends on ph
When is the structure of water disrupted
Ions in solution (when solid dissolves)
Partitioning
Distribution of a substance between two immiscible phases
Partition coefficient
Co / Cw
Co = conc. in organic phase
Cw = conc. in aqueous phase
Measure of relative affinity of the solute for an aqueous + lipid phase @ equilibrium
What does partition coefficient apply to
Dilute solutions e.g. ideal solutions
2 commonly used liquids to calculate P
Octanol + water
Why is octanol used?
Produces p values which correlate better with in vivo biological data
How is P calculated
Drug is added to separating funnel which contains the 2 immiscible liquids
Flask is shaken for up to 1 hour then left for phases to separate out
Concentration of aqueous phase is determined by either spectroscopy or titration
Concentration of organic phase is determined by subtraction
P can then be calculated
A suspension can become a…
Solution (+vice versa)
What can affect solubility
Solute substituents
How does solubility changes happen
Solute - solute
Highest relative permittivity of solvent
Water
What influences solubility of weak acid + weak base
pH
Calculate activity coefficient (y)
activity / concentration
when y (activity coefficient) = 1….
activity = concentration
When should activity be used
when dealing with strong electrolytes / weak electrolytes in solution with other salts
When can non-electrolytes + weak electrolytes have their activity = concentration
When present as the only species
Activity
reduction in the effective concentration
Real solution
Interactions between dissolved solutes which reduce the effective concentration
What solutions have their activity = concentration?
Ideal + dilute real solutions
Example of polar solvents
Water, methanol, acetic acid
What is the relative permittivity of polar solvents
High relative permittivity
What do polar solvents dissolve + how
Ionic solutes by reducing force of attraction between oppositely charged ions in crystalline solids
What bonds can polar solvents break
Covalent bonds
What solvent can solvate molecules + ions + how?
Polar solvents through dipole-dipole forces
What is wrong with ranitidine free base
Low aqueous solubility
Unstable to light
Sulfurous odour
How can we make ranitidine free base be absorbed
Reacting with HCl = Ranitidine HCl (salt)
Becomes odourless, stable + greater solubility
Examples of semi-polar solvents
Acetone, methanol, ethanol + other alcohols?
What can semi-polar solvents dissolve
Polar + non-polar substances
How do polar solutes dissolve
Dipole moment or H-bonding groups
How can semi-polar solvents be soluble in non-polar solvents
Inducing a degree of polarity
Examples of non-polar solvents
Hexane, Pentane, oils + fats, benzene
What is the relative permittivity of non-polar solvents
Low
What prevents non-polar solvents dissolving ionic/polar solutes
Lack of H-bonding
Non-polar solvents are unable to…
break covalent bonds
What can non-polar solutes dissolve
Non-polar compounds only
How are non-polar solutes held in non-polar solvents
Through van der waals interactions
Solubility equation of weakly acidic drugs
pKa = pH + log HA / A- pH = pKa + log S - So / So
Solubility equation of weakly basic drugs
pH = pKa + log So / S - So
S in solubility equation
Solubility of weakly acidic/basic drug at given pH
So in solubility equation
Solubility of undissociated drug
Example of amphoteric drugs
Oxytetracycline
Nitrazepam
Amphoteric drugs
Both acidic + basic groups so will have 2+ pKa values
What pH values can amphoteric drugs be ionised
All pH values
Isoelectric point
pH at which drug carries no net electric charge (equal dissociation of acidic / basic drug group
Calculate isoelectric point
(pKa1 + pKa2) / 2
When are amphoteric drugs are at its least solubility
At the isoelectric point (no net charge)
When do you use the basic drugs equation with amphoteric drugs
pH is below isoelectric point
When do you use the acidic drugs equation with amphoteric drugs
pH is above isoelectric point
Drugs with high log P can…
partition into rubber / plastic containers
- affecting many formulations
Which drugs are affected with high log P partitioning
Storage of lipophilic drugs
Ion-pairing
Ionised drugs combining with an oppositely charged ion
Ion pair behave as a neutral species and permeate through gastric mucosa
Substances that use active transport
Ions
Glucose
Vitamins
Amino acids
Melphalan
Similar to phenylalanine
Absorbed in GI tract
__________ drugs can also be absorbed in small intestines
Ionised
Structure of Water
104.5 degree bond angle
Tetrahedral
Form H-bonds
Flickering cluster model of water
Clusters of H-bonded ice-like water within pools of unbound (no hydrogen bonding) water
- clusters surrounded by fluid non-hydrogen bonded water
- ice-like clusters of H-bonded water
hydration
Ions have a layer of tightly bound water
Most small monoatomic ions have 4 water molecules bound in first shell, therefore hydration number is 4
What is Magnesium carbonate hydration number
5
Weak bases are likely to be ionised in the stomach so…
Cannot pass lipophilic gastric mucosa
How come ionised drugs can be absorbed in the small intestines
Large surface area
Good blood flow
Long residence time
