Physiochemical properties of drugs

What is autoionisation of water

Process in which water molecule produce hydrogen containing ions and hydroxide ions

Equation for water dissociation

H2O → H+ ions + OH- ions

What is hydronium ion

H+ ion not freely in water

Associated with water molecule

Form H3O+ ion

H+ conc when acid added

Increases

More acidic

H+ conc when base added

Decreases

Become more alkaline

Ionic product of water equation KW

Kw = (H+) (OH-)

Kw at 25 degrees

1 × 10 to -14

H+ conc and OH- conc at 25 degrees

1 × 10 -7

What happens to kw when temp increases

Kw increases

Why does adding a salt not always produce a neutral solution

Effect depends on acid and base from which salt was derived from

What does pH indicate

Indicates the acidity of a solution in relation to the hydrogen ion concentration

pH equation

pH = -log 10 ( H+)

pH unit

10 fold change

How many times greater is the hydrogen conc in pH 2 than pH 4

100 times greater

4-2 =2

10 squared is 100

pH affected by 2 factors

Hydrogen ion concentration

Strength of the acid and type

Strong acid

Fully ionises in an aqueous solution

Weak acid

Partially ionises in an aqueous solution

What is a pH indicator

Organic compound that changes colour over a defined pH range

Why can’t indicators measure pH accurately

As the colour changes over a range of pH values

Methyl orange

Red acid

Yellow base

Methyl red

Red acid

Yellow base

Litmus

Red acid

Blue base

Thymol blue

Yellow acid

Blue base

Alizarin yellow

Yellow acid

Lilac base

Arrhenius acid

Produce H+ ion in aqueous solution

Arrhenius base

Produce OH- ions in aqueous solution

Bronsted Lowry acid

Proton donor

Bronsted Lowry base

Proton acceptor

Conjugate base

What remains after an acid donated a proton

Conjugate acid

What forms when base accepts proton

Amphoteric and example

Act as both an acid and base

Water

Lewis acid

Electron pair acceptor

Lewis base

Electron pair donor

Acid characteristics

Sour taste

React metals

Hydrogen in description

Poisonous

Corrosive

Base characteristics

Bitter

Slippery

Hydroxide ions

String base poisonous and corrosive

Neutralisation reaction

Acid + base → salt + water

Exothermic

56kjmol-1

Lewis and Bronsted Lowry acid

All Bronsted Lowry acids are Lewis acids Proton accept pair of electrons from base

But not all Lewis acids are Bronsted Lowry acids e,g bf3 and nh3

Ka

Acid dissociation constant for weak acid

How much acid dissociate ions at given temp

Ka expression

Ka = (h+) (a-) / (ha)

Large Ka

Stronger acid

More dissociation

Small Ka

Weaker acid

Less dissociation

Pka equation and what is it

-log 10 Ka

How easy acid loses a proton

Small pka

Large Ka

Strong acid

Large pka

Small Ka

Weak acid

Relationship between ph and pka

pH = pka

Acid 50% dissociated

pH 1 unit above pka

Acid 90% dissociated

pH 2 units above pka

Acid 99% dissociated / ionised

1 % unionised

pH 1 unit below pka

Acid 10% dissociated

90% unionised fo

Acidic drug when pH above pka

More of acid in its ionised form

A-

What does ionisation affect for the dug

The drugs solubility and movement through membranes

Unionised

Still has H+ ions

pH > pka

More than 50 % ionised

Loses H+ ion readily

pH > pka

More than 50 % ionised

Loses H+ ion readily

pH < pka

Acid keeps its H+ ion

Ph and pka forumla for ionisation

pH = pka + log 10 ( a-) / (ha)

Weak base ph above pka

Unionised

Lose tendency to accept h+ ion because solution has lower conc

Weak base ph below pka

Ionised

BH+

What is a buffer

A solution that resists changes in pH when small amounts of acid or alkali are added

Ph changes slightly

Diluting a buffer does not change its pH but reduces buffer capacity

Buffer made out of

Weak acid and its salt That can supply its conjugate base

Weak base and its salt

Buffer capacity

Amount of acid or alkali buffer can resist before pH changes substantially

Henderson hasselbalch equation

pH = pka + log10 (a-) / (ha)

Weak base just change. (B)/ (bh+) unionised / ionised

Fraction of acidic drug unionised

Fu = 1 / 1 + 10 ( ph - pka)

Fraction of basic drug unionised

1 / 1 + 10 -(ph- pka)

Water soluble

Ionised form

Lipid soluble / pass membranes

Unionised

Understanding pH and pka

• Behaviour — how the drug behaves in different environments.

• Formulation — how the drug is prepared into a suitable medicine.

• Processing conditions — the conditions needed when manufacturing a drug.

• Dissolution — how the drug dissolves.

• Absorption — how the drug enters the bloodstream.

• Distribution — how the drug moves around the body.

• Elimination — how the drug is removed from the body.

What does ionisation affect

If it can cross membrane or is soluble

Solution definition

One phase system

Solute dissolved in solvent

Solute

Substance being dissolved

Solvent

Greater quantity

Dissolve solutes

Dissolution

process of Substance dissolving in a solvent to make homogeneous solution

Drug needs to dissolve before absorbed

Saturated solution.

Max amount of solute dissolve at given temp and pressure

Unsaturated solution

Less dissolved solute

Solubility

How much a substance can dissolve

Hydrophilic

Water loving

Favourable interaction

Hydrophobic

Water fearing

Interact poorly with water

Drug solubility

Drug need to dissolve before absorbed

Solubikgy affect how well absorbed

What affects drugs water solubility

Polar groups OH interact water and increase solubility

Non polar regions e.g hydrocarbon chains reduce water solubility

Maximum solubility

Equilibrium solubility

maximum amount of a substance that can dissolve in a solvent under specific conditions, such as temperature, pressure and pH.

Crystalline solid

Atom molecule ions arranged 3d pattern

Slower dissolution rate

Lower solubility

More energy separate

Amorphous solid

Lack ordered / regular arrangement found in crystal

Higher solubility

Faster dissolution rate

Less energy separate

Crystalline and Amorphous important

Affect drugs solubility and dissolution rate

If you want a drug to cross a lipid cell membrane it must be:

Unionised

Making it lipid soluble Allowing it to absorb well

If it is ionised

It won’t cross membrane easily

As it is water soluble

So poor absorption

GI absorption

Drug moves from your gut into your blood

Only happens easy if drug is unionised

How do you want the drug to be when dissolving in water or bodily fluids

Ionised form

Water soluble

Dissolves well in gut fluids, blood and cell fluid

This is because water is polar and has a charge

Water surrounds and spreads evenly around the drug

What’s the purpose of enteric coating

Protect drug from stomach acid

Release drug in intestine

Why are some drugs in salt forms

Salts are more ionised so dissolve better in water

Once dissolved, body pH convert some back to unionised for absorption

Why do drugs need to be both ionised and unionised at different points

Ionised first means it will dissolve in gut fluid

Then unionised as it will cross lipid membrane into blood

Need both steps for good absorption

Solubilisation process

1) separate solute molecules

Molecule in drug separate from one another use energy to overcome intermolecular attraction

2) create cavity in the solvent

Solvent molecules move apart to make room for drug / space for solute molecules

Requires energy

3) solute/ drug enters the cavity interact with the solvent molecules

New attractions help stabilise the dissolved drug

Quantitative solubility

Express numerically using value and units

Qualitative solubility

Describe solubility using words

E.g soluble or insoluble

Difference between molarity and molality

Molarity uses volume in L

Molality uses mass if solvent in Kg

Like dissolves like

Polar solvent dissolve polar molecule / ions

Non polar solvent interact non polar substances

Polar vs non polar

Polar has uneven distribution of electrical charge

Non polar has no overall separation of electrical charge

Electronegativity

Power of an atom to attract a pair of electrons in a covalent bond

What is dipole moment

Measure of separation of positive and negative charge

What is the dielectric constant relevant to

How a medium responds to electric field

And how reduces electrostatic interactions between charges

Why is water important in pharmacy

Water is polar Solent

Affect bioavailability of drug and its pharmacological action

Bioavailability

Gets affected by drug ability to dissolve in water

Proportion of administered drug that reaches the systemic circulation

How quickly it gets there

Water

Partially negative oxygen

Partially positive hydrogen

Bent shape

Polar as dipoles don’t cancel