TBL 3 - PHYSIOCHEMICAL PROPERTIES OF DRUGS Flashcards
What type of acid is water?
H2O is a weak acid and will dissociate in water.
What are H+ and OH- ions?
H+ are free + charged H ions and OH- are free negatively Hydroxide ions
what happens when H+ is attached to H2O?
Forms HYDROXONIUM ION (H3O+)
What happens to the H+ when you add acid to water?
- Increases H+ (H3O+) conc
what happens to the H+ when you add acid to water?
Increases H+ (H3O+) conc
What happens to the H+ when you add base to water?
decreases H+ conc (H3O+)
what is the PH range of the natural water?
6 .5 to 8.
what is the symbol of the dissociation of water?
Kw
what happens when pure water dissociate?
yields 10^-7 moles/L of H+ at 25 C
What happens when water is neutral?
dissociates to product 1 OH- ion for each H+ ion simultaneously
What is pH expressing?
H ion conc in water - pH relates to the acidic and alkaline nature of water.
What is PH used to measure?
the acidity of a solution. pH stands for potential hydrogen and its a measure of how many H+ ions are there in a solution.
what is the formula for pH?
pH = -log10[H+] = log10 1/[H+]
What happens to the pH when there’s more H+?
More H+, lower pH
What happens to the pH when there’s less H+?
less H+, higher pH
What are the 2 things that the pH of a solution depends on?
- Conc of solution: if 2 solutions have same acid more concentrated solution will have more free H+ ions so lower pH
- Acid in question: 2 equally concentrated solution of acids the solution of the strong acid will have a lower pH then a weak acid cus it’s more fully dissociated and produces H+ ions. e.g HCl fully dissociated.
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What is the definition of pH?
pH is a measure of acidity of a given solution
what is the range of the pH?
0 to 14 Neutral = pH 7 @ 25 C
What happens to the pH when acid conditions increases?
acid conditions increase as pH decreases.
What happens to the pH when alkaline conditions increase?
alkaline conditions increase as pH increases
what happens if the numerator is greater than denominator?
Ka is large and acid is strong.
what happens if the numerator is less than denominator?
-Ka is small and acid is weak.
In the formula: HA (aq) + H2O (l) = H3O+ (aq) + A- (aq) why do we ignore the H3O+ present?
Due to auto-ionisation of water which H3O+ and A- conc is thought to be the same leading to [H3O+][A-] = H2O^2.
What is a weak acid?
is an acid that can partially dissociate in water.
what is a strong acid?
an acid that can completely dissociate in water.
Using the indicator methyl orange what would be the acid and base colour and pH range of colour change?
Acid = red, Base = yellow-orange and pH range = 3.1 - 4.6
Using the indicator methyl red what would be the acid and base colour and pH range of colour change?
acid=red, base=yellow and pH range= 4.4-6.2
Using the indicator litmus what would be the acid and base colour and pH range of colour change?
acid=yellow, base=blue , pH range = 8.0 to 9.6
Using the indicator thymol blue what would be the acid and base colour and pH range of colour change?
acid=yellow, base=blue , pH range = 8.0 to 9.6
Using the indicator phenolphthalein what would be the acid and base colour and pH range of colour change?
acid = colourless, base= pink and pH range = 8.2 - 9.8
Using the indicator alizarin yellow what would be the acid and base colour and pH range of colour change?
acid = yellow, base = lilac , pH range = 10.1 to 11.1
what is Arrhenius definition of an acid?
is a substance that contains H+ and dissociates into water to yield a hydronium ion (H3O+)
what is Arrhenius definition of a base?
substance that contains hydroxyl group and dissociates in water to yield a hydroxyl ion (OH+).
What is a neutralisation?
reaction of an H+ (H3O+) ion from acid OH- from base to form H2O
What is the restriction to the arrhenius definition?
being only restricted to an aq solution
What is the bronsted-Lowry definition for acids?
a species having a tendency to LOSE(donate) a proton (H+) - acid must have H in its formula
What is the bronsted-Lowry definition for a base?
a species having a tendency to accept a proton (H+) - likes to bind to H+ ion e.g. NH3, CO3, OH-
Formula for bronsted-lowry definition is…
AH + B reversible reaction A- + BH+ (AH = acid, A- = conjugate base, B= base, BH+ = conjugate acid
- What is a conjugate base?
basic form of a given acid if it accepts proton becomes an acid
What is a conjugate acid?
the acidic form of a given acid if it donates a proton it becomes a base.
Why is water an amphoteric compound?
it has the ability to act as both an acid and a base
What is the Lewis definition (hint electrons)?
an electron-pair accepted
What is a Lewis definition for a base?
an electron-pair donor
What are the characteristics of acids (4 things)?
- sour taste
- Reacts with metals
- Contain H+
- Poisonous/corrosive to skin
What are the characteristics of bases (4 things)?
- Bitter taste
- Slippery
- Contain oh- ions
- Strong bases can be poisonous/corrosive to skin
What do strong acids do?
break down completely to give off many H+ ions e.g. HCl
- What do weak acids do?
partially break down gives off less H+ e.g. acetic acid
Examples of strong acids….
- Sulphuric acid ( H2SO4)
- Hydrochloric acid (HCl)
- Hydrobromic acid (HBr)
- Hydroiodic acid (HI)
- Nitric acid (HNO3)
- Perchloric acid (HClO4)
Examples of strong bases…
- Lithium hydroxide (LiOH)
- Sodium hydroxide (NaOH)
- Potassium hydroxide (KOH)
- Calcium hydroxide (Ca(OH)2)
- Strontium hydroxide (Sr(OH)2)
- Weak acid examples….
- Aceitic acid (vinegar) (HC2H3O2)
- Carbonic acid (HCO3)
Weak bases examples…
- Hydroxides of group 1/2 metals are strong others weak.
What is neutralisation?
acid and base react together
what does salt mean?
any ionic compound formed from an acid/base reaction
What is Ka?
the dissociation constant for a compound at a given temp. position of equilibrium is measured by acidity constant
Ka expressed as….
pKa = -log10 ka
What happens to the acid as the pKa value increases?
Lowers the Ka, weaker the acid.
what happens to the acid ad the pKa values decreases?
higher Ka, stronger the acid.
What happens when the pH is above the pKa?
acid exists as A- in water and will be soluble.
what happens when pH is below the pKa?
acid exists as HA in water and less soluble
What is the Ka?
is the dissociation constant for the ionisation of an acid.
What happens when the Ka was large?
stronger the acid.
What is pKa?
the negative logarithm of Ka.
What happens when the pKa value is smaller?
stronger the acid.
what happens to the acid when the pH was higher than pKa?
acid more then 50% dissocaited.
What happens to the acid when the pH was less than the pKa?
acid less than 50% dissociated.
What is a buffer?
a solution with known pH and resists changes in pH
what is a buffer composed off?
weak acids & their salts or weak bases and their salts
when does optimal buffering occur?
occurs at pH between pKa +1 and pKa -1 when pKa represents pKa of conjugate acid in buffer system.
what is the use of the Henderson-Hasselbalch equation?
predicts pH of buffers as a function of pKa.
When does ionisation of drugs happen?
when weak acid or basic drugs ionise or become protonated.
what is the ionisation dependent on?
on the pKa of drug and pH of body fluid it’s dissolved in.
what is the pH of blood?
7.4
What are some acidic drugs?
aspirin and paracetamol
What is the pKa of aspirin?
3.5
What is the pKa (acidity of a particular molecule) of paracetamol?
9.5
what are some basic drugs?
diazepam and diphenhydramine
What is the pKa of diazepam?
3.3
what is the pka of diphenhydramine?
9.0
what are some amphoteric drugs?
morphine and adrenaline
What is the pKa of amine and phenol of morphine?
8.0 for amine and 9.9 for phenol
what is the pKa of amine and phenol of adrenaline?
8.7 amine and 10.2, 12.0 phenol
why should a drug be dissolved in water?
to allow to cross biological membranes to reach its pharmacological target and elicit a therapeutic effect
If a drug shows poor aq solubility what problems will it present?
problems with bioavailability and formulation
What is the definition of a solution?
a solution a one phase system (usually liquid) which consists of solute molecules which is dissolved within a solvent vehicle.
what is the definition of a solute?
A solute refers to a substance which is dissolved in solution. solute present at a lesser quantity then the solvent.
What is the definition of the solvent?
a solvent is a substance that is used to dissolve a solute . solvent is a component which is present in greater quantity. - component present is in excess.
What is dissolution?
Involves the preperation of a solution by mixing together a solute and solvent until a homogenous liquid (solution) is obtained.
what is a saturated solution?
when a solution contains a solute at the limit of its solubility (at given temp/pressure)
what is an unsaturated or sub-saturated solution?
When the dissolved solute is at a conc below that necessary for complete saturation of the solvent.
What is a supersaturated solution?
where the solute exists in solution above its normal solubility limit. can be obtained by altering the temp, volume or pressure.
what is an example of a supersaturated solution?
carbonated water (soft drinks)
What is a crystalline solid?
a solid where its atoms, molecules or ions arranged in an ORDERED 3D pattern.
what is an amorphous solid (non-crystalline solid)?
Lacks the ordered characteristics of a crystal.
What is hydrophilicity?
affinity of a compound to water (water-loving)
What is hydrophobicity?
repulsion of compound from water (water-fearing)
What is the maximum solubility (equilibrium solubility)?
maximum amount of solute that can be dissolved in solvent under specific conditions (pH, temp, pressure)
what is the basic solubilation process (3 steps)?
1) solute molecule removed from bulk structure - breaking bonds. Crystal structures HIGHLY ORDERED/TIGHTLY PACKED. So, STRONG INTERMOLECULAR BONDS requiring more ENERGY TO BREAK apart then amorphous (unordered) solids. - Crystals have HIGH MELTING POINT, LOW WATER SOLUBILITY
2) Cavity CREATED in solvent
3) SOLUTE MOLECULES INTSERTS ITSELF into CAVITY and INTERACTS with SOLVENT MOLECULES forming BONDS.
How is solubility expressed?
- Mole fraction
- Molarity- number of moles of solute dissolved in 1 litre of solution (mol L^-1)
- Molality - number of moles of solute dissolved is Kg of solvent (mol Kg^-1)
- weight concs - mass of solute per 100 ml of solution (%W/V) or mass of solute per 100g of solution (% W/W)
- parts per million (PPM)
What is the basic rule of solvents?
like dissolves like e.g. polar solvents dissolve polar solutes - O2 in H2O and ethanol in H2O
What do polar solvents contain?
contain bonds between atoms with different electronegativities. so have strong dipole moments, characterised by high dielectric constants and will dissolve ionic solutes and polar substances. e.g. water dissolves sugars and alcohols.
what is the most common polar solvent in pharmaceutics?
Water - needed since drugs solubility in water is required to ensure bioavailability and pharmacological action in the body
What is the structure of water?
1 electronegative O2 atom and 2 H atoms connected via polar bonds.
Why is water a polar bond?
high electronegativity of O2 compared to H means electrons within these bonds are unequally shared including partial charges giving its polarity.
What bonding is used for water when trying to bond to neighbouring water molecules?
Hydrogen bonding. H2O contains 2 potential H-Bond donors (polarised hydrogens) + 2 H-Bond acceptors (lone pairs of electrons)
What is the physical structure of water?
water is transient(ever changing), contains highly ordered regions, disordered areas, multiple cavities/holes where solutes can enter.
Non-polar solvents dissolve non-polar solutes what is an example of this?
iodine in hydrocarbons e.g. hexane
What do non-polar solvents contain?
contain bonds between atoms with similar electronegativities and have low dielectric constants . So, polar solutes will not dissolve.
What are 2 things that dissolve readily in non-polar solvents?
OILS/FATS e.g. carbon tetrachloride (2.2) or octane (1.9)
What happens to the solubility when you increase the temp (4 things)?
- Increases solubility of solids.
- Increasing KE of system, causing solute dispersion to increase exposing solute to fresh solvent faster.
- dissolution represents change in state (solid to liquid) requires energy (heat) to break bonds present in bulk structure.
- Solid/liquid systems increasing pressure has no effect on solubility. but with gases dissolved in liquid - increasing pressure increases their solubility as they form supersaturated solutions.
What is the body temp and pressure In human beings?
36.5 C and 1 ATM
How are the melting point related to solubility?
solubility and melting point involve phase change from solid to liquid. both dependent on the energy needed to break/from intermolecular bonds. HIGH MELTING POINT = POOR WATER SOLUBLITY
How are molecular shape and symmetry related to solubility?
how well molecules packed together in solid (crystal) state. symmetrical, flat molecules can pack tightly together with stronger intermolecular forces. leads to HIGH MELTING POINT, LOWER AQ SOLUBILITY
How does increasing molecular weight relate to solubility?
decrease the water solubility as increasing molecular weight equates to increased non-polar (hydrophobic) nature. drugs with molecular weight >500 Da shows low solubility. if it’s above 1200 Da should be avoided.
How does hydrogen bonding ability affect solubility?
can increase solubility since it can form H-bonds with polar solvents. but strong H bonding between neighbouring solutes molecules can form leads to reduced solubility.
How does polar (ionisable) functional groups affect solubility?
increases solubility - acid/bases in charged forms more soluble.
- How does non-polar functional groups affect solubility?
decrease solubility as increase hydrophobic (water-hating) character of solute as they disrupt H-Bonding of H2O.
why is pH important for drugs?
determines proportion of a ionisable drug that is charged (protonated or deprotonated)
What happens to the acid and the solubility of water at low pH (<4)?
at low pH acid is in its free (uncharged) state/ solubility in water is low.
What happens to the acid and the solubility at a higher pH (>5-6)?
acid is deprotonated, becomes - charged and H-bond with water. increases water solubility
what is intrinsic solubility?
solubility of the free (un-ionised) solute
what are colligative properties?
the amount of solute present affects the properties of the solution.
what is osmosis?
net movement of solvent (water) molecules through a partially permeable membrane driven by the difference in solute concs on 2 sides.
What is osmotic pressure?
pressure needed to stop movement of water.
What is the name used for the osmotic pressure gradient of 2 solutions separated by a semipermeable membrane?
Tonicity
- what is a hypertonic solution?
cell placed in solution will high solute conc - cell will shrink and lose water.
- what is isotonic?
Ratio of solute and water is equal.
what is the tonicity of blood plasma?
275-295 mOsmol Kg^-1 - so tonicity of liquid preparation coming into contact with body must to equivalent to blood.
What is the connection between hydrophobicity and water solubility?
inversely related (increasing water solubility decreases hydrophobicity)
What are the factors affecting hydrophobicity (4 things)?
1) molecular weight (mw) - increasing mw increases non-polar character of a compound, INCREASING HYDROPHOBICY nature.
2) polarity - addition of polar (ionisable) functional group increases water solubility, DECREASES HYDROPHOBICY
3) pH - free (unionised) forms of drugs less water soluble, greater solubility in non-polar solvents.
4) H bonding ability- compound form H bonds with water (or to other polar solvents) usually highly water soluble - INCREASING H BOND DEACRESE HYDROPHOBICITY
What is miscibility?
when liquids form homogenous solution.
what is immiscible?
when liquids form non-homogenous mixtures
What happens when 2 liquids are immiscible?
form distinct layer most dense liquid falls to the bottom e.g. olive oil at the top - non-polar - hydrophobic, water at the bottom - polar - hydrophilic.
What is partitioning?
adding a third substance to assess its hydrophobic or hydrophilic nature
Partitioning process:
1) add 3rd substance to oil/water system.
2) distribute itself between 2 layers (known as partitioning)
3) if substance hydrophobic will concentrate within oil (non-polar) phase. hydrophilic will concentrate in aq phase
How is partition quantified?
partition coefficient (P)
What is the ratio of conc of a substance between 2 immiscible phases called?
K or Kow when octanol: water system used.
what does the logarithm of partition coefficient give?
Log P
What is partitioning log p a measure of?
measure of compounds hydrophilic and hydrophobic nature and provides insights into drugs bioavailability when it enters body.
what happens when a drug is too hydrophilic?
will have excellent water solubility but wont be able to cross biological membranes as they have hydrophobic characteristics.
what happens when the drug is too hydrophobic?
drug would have poor water solubility and would enter but not leave the cell membrane.
what role does hydrophobicity play in?
role in determining drugs ADME profile. and plays role in receptor binding
- absorption of oral formulations through GI tract - drug pass into bloodstream, pass through lipid bilayers (membrane) of intestinal epithelium. Drug must be hydrophobic enough to partition into lipid bilayer membrane but not so hydrophobic that it is unable to partition back out again.
Why is octanol used as a non-polar solvent in log p determinations?
cus structure of octanol resembles amphiliphilc form of a phospholipid - polar head and hydrophobic tail.
