MP2 Physical and Chemical Properties of Solutions 1-3

Miscibility

Ability of 2 substances to form a homogenous molecular dispersion when mixed in any proportion e.g. ethanol in water

Partial miscibility

2 substances that form a homogenous molecular dispersion when mixed in some proportions / at certain ratios e.g. nicotine: water

Immiscibility

inability to form a homogeneous molecular dispersion e.g. olive oil in water

Ionisability of 1. non-electrolytes

2. weak electrolytes

3. strong electrolytes

1. None as there are no ions

2. Weakly ionised

3. Completely ionised

Electrolyte

A substance that dissolves in water to produce positive and negative ions, allowing the solution to conduct electricity

Pure and normal water conductivity

Pure water: can't conduct as it's DI

Tap water: Weak conductor

Normality

the number of equivalents (reactive species) of a substance dissolved in a liter of solution

mEq

number of charged species in solution

Colligative properties

i.e. solute type doesn't matter, only particle number (concentration) in solvent does!

4 colligative properties are:

1. Vapour pressure lowering

2. Boiling point elevation

3. Freezing point depression

4. Osmotic pressure

Ionic vs. non-ionic effect on colligative properties?

Ionic solutes dissociate and produce more particles so have a multiplied colligative effects e.g. NaCl dissociates into Na+ and Cl- so has a doubling effect

Volatile liquid

liquids that evaporates readily and has a high vapour pressure e.g. ethanol

Raoult's Law

The vapour pressure of a solution is proportional to the mol fraction of solvent i.e. the higher the solute concentration = the lower the vapour pressure of the solvent = the less evaporation.

What's the vapour pressure of two volatile solvents mixed together according to Raoult's Law?

VP = weighted mean of each solvent

Ideal solution

Solution with uniformity of intermolecular forces. Solvent/solvent, drug/drug, and solvent/drug interactions are all equal.

Ideal solutions have:

1. Thermoneutral dissolution

2. No enthalpy change so ΔH = 0

3. Components obey Raoult's Law

Real/non-ideal solution (Most pharmaceutical solutions)

Solution with unequal forces of attraction between solvent/solvent, drug/drug, and solvent/drug.

VP graph x and y axis

x-axis: mole fraction (basically solute conc.)

y-axis: vapour pressure

Identifying ideal and real solutions on a VP graph

Ideal: linear line

Real: non-linear

N.B!! What excipient slows down evaporation and how?

Humectants can slow down evaporation by lowering the vapour pressure of the solvent to prevent drying out

Boiling Point Elevation and Freezing Point Depression overall relationship

High solute concentration = lower VP = lower evaporation = increased BP = decreased FP

BP elevation formula

Tb = i x Kb x m (m: molal concentration)

FP depression formula

Tf = i x Kf x m (m: molal concentration)

What do Kb and Kf stand for

Kb: BP elevation constant

Kf: FP depression constant

(Note: they differ depending on the solvent!)

The higher the Kb or Kf values...

...the more sensitive the solvent is to the addition of solute

Osmotic pressure

Pressure required to prevent osmosis

Osmotic pressure relationship

The higher the solute concentration = the higher the osmotic pressure = the higher the hypertonicity

Osmotic pressure formula

π = iMRT

Osmotic pressure formula key

π: osmotic pressure

i: Van't Hoff Factor

M: Molar concentration of solution

R: Ideal gas constant

T: Absolute temperature (Kelvin)

Tonicity

Osmotic pressure in cells

Osmosis

Diffusion of water through a selectively permeable membrane (inside to outside of cell; causes cell to shrivel)

Hypertonic

[solute]ins < [solute]out

Isotonic

[solute]ins = [solute]out

Hypotonic

[solute]ins > [solute]out

Ionisable vs. non-ionisable species

Ionisable: can dissociate into ions e.g. NaCl

Non-ionisable: can't dissociate into ions e.g. glucose

How to tell if ionisable?

If you see:

1. Metal + non-metal e.g. NaCl

2. Acid, so has H at start e.g. HCl or HNO3

3. Base, so has OH at end e.g. NaOH or KOH

4. Weak acid, so has a carboxylic group e.g. CH3COOH

How to tell if non-ionisable?

If you see:

1. Only C,H,O atoms e.g. glucose or ethanol, it's neutral covalent

Van't Hoff Factor (i)

Tells you how many ions/molecules a solute produces when dissolved in a solvent

The higher the particle/solute concentration...

...the stronger the effect on colligative properties

Van't Hoff Factor Equation

i = moles of particles in solution / moles of starting molecule (just go off molar ratio)

Van't Hoff Factors for 1. Non-electrolytes

2. Weak electrolytes

3. Strong electrolytes

1. i = 1

2. i = between 1 and the number of mols of particles in solution (top # in eq!)

3. i = Total number of mols of particles in solution (top # in eq!)

Buffer

Blend of a weak acid and it's conjugate base (or a weak base and it's conjugate acid) to lock pH in e.g. acetate buffer is made up of acetic acid and sodium acetate with a pKa of 4.74

How is buffering capacity defined?

Henderson Hasselbatch equation

Buffers are used within...

...1 pH unit of their pKa

pKa

Measure of the strength of an acid in solution. It’s the pH at which 50% of species are available to accept protons, and 50% are available to donate protons (i.e. 50% ionised and 50% unionised)

pH of the salt of a weak acid

High pH

pH of the salt of a weak base

Low pH

Absorption

Penetration from one phase into another (into the bulk of a phase)

Adsorption

Binding to the interface

Interface

Boundary between phases

2 types of adsorption

1. Physisorption (most drugs!)

2. Chemisorption

Leaching

Loss of materials from the packaging into drug solution

What do plasticisers do and an example of one?

Make polymers softer by lowering the glass transition temperature (TG) e.g. DEHP is a plasticiser used in PVC bags and certain solutions can leach it out of the bags and into solution

What has LogPHexane: water been used for?

To determine the absorption of drugs into plastic materials

Chelation

Binding of a metal with a ligand which can effectively remove the metal from solution or reduce its reactivity

Chelates

Antioxidant excipients that can be used to prevent oxidation e.g. EDTA used to prevent poisoning

Precipitation is the...

...reverse of dissolution

What is precipitation?

Process whereby the solute loses its affinity for the solvent its dissolved in and reverts to its solid form. Want to avoid for ophthalmic and injectable routes!

Ritonavir Case

Ritonavir formed a less soluble polymorph and cause precipitation which has huge consequences

Cation and anion interactions

Mixture of a solvated cation and anion can result in the formation of an insoluble precipitate

Models of type I adsorption isotherms

1. Langmuir

2. Freundlich

What do the type I adsorption isotherms quantify?

% drug binding per mole of adsorbent

The more drug you have...

...the more adsorption you have

How does solute concentration affect adsorption?

The higher the solute conc, the higher the adsorption up until a certain point where it levels off

How does temperature affect adsorption?

The higher the temperature, the lower the adsorption

How does pH affect adsorption?

Acids have maximal adsorption at low pHs

Bases have maximal adsorption at high pHs

(i.e. at their own pH)

How does solubility affect adsorption? (rule)

Lundilius' rule states that higher solubility = lower adsorption.

In summary, a lipophilic, unionised drug is more likely to adsorb to lipophilic surfaces like plastic

Ionised drugs' solubility and adsorption relationship

Ionised drug = better water solubility = lower adsorption to lipophilic surfaces

In what way do gases and drugs bind?

Gases bind in a multilayer, drugs bind in a monolayer

Relationship between adsorption and surface area

Extent of adsorption is proportional to the surface area

You get standard adsorption when...

...you have a lipophilic, non-ionised drug and a lipophilic surface

You get massive adsorption when...

...you have an ionised (charged) drug and an oppositely charged surface (due to the electrostatic, ionic attraction)

You get low adsorption when...

...1. you have an ionised drug and a lipophilic surface because the ionised drug prefers water.

2. you have a similarly charged (ionised) drug and surface

Surfactant adsorption

Surfactants adsorb efficiently as they preferentially seek out interfaces

Rheology

study of deformation and flow

Stress

Force applied per unit area (Pa)

Strain (γ)

Deformation under stress

Viscosity

resistance to flow