PPFA 10 - Equilibrium - Buffers

understand how buffers resist PH change, apply henderson- hasselbalch equation ,buffer capacity and clinical uses of buffers in pharmacy

What is the relationship between hydrogen ion concentration and ph ?

At 25 degrees water dissociates into hydroxyl and hydrogen ions bothe present in equal concentrations of 1×10-7 mol/L= balance makes water neutral PH=7 

• PH is defined as the negative log of H+ 

                   𝑝𝐻 = −𝐿𝑜𝑔10 𝐻+

So, when [H⁺] = 1 × 10⁻⁷, the pH = 7 i.e Neutral

What happens if we add an acid or a base?
If we add an acid, it donates protons ⟶ 𝐻+ increases ⟶ ⟶ pH < 7
If we add a base, it accepts protons ⟶ 𝐻+ decreases ⟶ ⟶ pH > 7

How big is the range of H= or  PH ?

From about 1 mol/L for a strong acid, down to 1 × 10⁻¹⁴ mol/L for a strong base.

pH range 0-14

How do we measure PH ?

• indicators

• ph probe - need calibration

• indicator paper

What are the physiological Phs of the body ?

• general ph = 7.4 and fluctuates around this

• stomach significantly lower- acidic 1-3

• small intestine fluctuates

What is the clinical significance with regards to the blood ph ?

Normal arterial blood- 7.4 

Venous blood and interstitial fluids - 7.35 ( slightly lower due to more co2 - more carbonic acid )

• if blood PH <7.35 ( acidosis) - CNS depression - confusion ,disorientation , coma 

• if blood PH> 7.45 ( alkalosis ) - CNS hyperexcitability - muscle spasms ,convulsions ,respiratory paralysis 

survival limits:

Lower limit ≈ 7.0 (survival for only hours)
Upper limit ≈ 7.7

Fatal range:
< 6.8 or > 8.0 → death occurs quickly

What is the importance of ph in pharmaceutics ?

• It affects the ionisation of weak acids and bases, which changes how drugs dissolve and absorb
  ▪ It influences drug solubility
  ▪ And importantly, it impacts drug absorption across membranes into the
  bloodstream

Absorption patterns for weak acid and weak bases ?

For weak acids- needs to be unionised for absorption

For weak bases - needs to be ionised for absorption

What are the dissociation of acids and bases equations and its constant ?

For a weak acid (HA) HA ⇌ H⁺ + A⁻
For a weak base (B) B + H⁺ ⇌ BH⁺

The acid dissociation constant (Ka) measures how much an acid dissociates
To simplify numbers, we use pKa instead;

pKa = -log₁₀Ka

A lower pKa means a stronger acid (it dissociates more easily)

What is the buffer equation - henderson - hasselbalch equation ?

Relationship Between pH, pKa, and Ionisation

From the Henderson–Hasselbalch equation:

For weak acids pH = pKa + log([A⁻]/[HA])
For weak bases pH = pKa + log([B]/[BH⁺])

These equations show how pH and pKa determine the ratio of ionised to unionised
drug

What is the relationship between pKa and Ph ?

• The degree of ionisation

• When pH = pKa, the drug is 50% ionised and 50% unionised

- If pH > pKa → acidic drugs are mostly ionised at high ph

- If pH < pKa → basic drugs are mostly ionised at low pH

Unionised form = more lipid-soluble and better absorbed

• Ionised form = more soluble, less
  absorbed

What is a buffer ?

Buffer solutions resist changes in pH when small amounts of acid or base are added.

What is the importance of buffers in their applications ?

• Maintain ph

• Blood contains acids from metabolism all the time - lactic acid ,carbonic acid - blood ph barely changes

• Medications need buffers to resist ph change

What does a buffer consist of ?

They consist of either:

Weak Acid + Conjugate Base (Salt)
HA (weak acid) and A⁻ (from salt like NaA)

• Added H⁺ reacts with A⁻:
A⁻ + H⁺ → HA pH resists change

• Added OH⁻ reacts with HA:
HA + OH⁻ → A⁻ + H₂O pH resists change

Weak Base + Conjugate Acid (Salt)

B (weak base) and BH⁺ (from salt)

• Added H⁺ reacts with B:
  B + H⁺ → BH⁺ pH resists change
  

• Added OH⁻ reacts with BH⁺:
  BH⁺ + OH⁻ → B + H₂O pH resists change

What is buffer capacity ?

Buffer Capacity (β) measures how well a buffer resists changes in pH when acid or alkali is added.

It is defined as the amount of acid or base (in moles) needed to change the pH of 1 litre of solution by one unit.

If adding 1 mole of alkali changes the pH by 1, then β = 1

The buffer capacity depends on the total concentration of the buffer and the pKa of the weak acid

Key points:
Buffer capacity is highest when pH = pKa

graph - Buffer capacity of acetic acid–acetate
buffer as a function of pH

Why is physiological buffer capacity crucial?

To prevents dangerous swings – small pH shifts impair enzymes, large shifts cause coma/death

What is a chemical buffer system ?

Chemical buffer systems in body fluids that quickly neutralise added acids or bases to stabilise pH within second

What is a physiological system ?

Physiological systems that act more slowly:
• Respiratory system: Adjusts breathing rate to control carbon dioxide (CO₂)
levels, which affects blood pH. This takes a few minutes
• Urinary system (kidneys): Removes excess hydrogen ions (acid) through urine, slowly restoring pH over hours

What is bicarbonate buffer - ( major chemical buffer) ?

Bicarbonate buffer:

• Made of carbonic acid (H₂CO₃) and bicarbonate ions (HCO₃⁻).
  Neutralizes acids by converting bicarbonate to carbonic acid, which breaks down to water and CO₂ (exhaled).

• Neutralizes bases by converting carbonic acid to bicarbonate.

• Although its buffering capacity is not maximal at blood pH (~7.4), it’s efficient because it self-regulates via respiration and kidney function

What is a Phosphate buffer- major chemical buffers ?

Phosphate buffer:

• In cells, uses dihydrogen phosphate (H₂PO₄⁻) and hydrogen phosphate (HPO₄²⁻) ions to buffer pH near 7.2, closer to physiological pH than bicarbonate, but at lower concentration.

What is a Protein buffer - chemical buffer?

Protein buffer:

• The most powerful system, accounting for ~75% of body’s buffering capacity.

• Proteins buffer via acidic (–COOH) and basic (–NH₃) groups on amino acids, with pKa values near physiological pH, making them very effective.

Key Points:
The body uses fast-acting chemical buffers and slower respiratory and kidney
mechanisms to tightly regulate pH, crucial for normal function and health.

What is a universal buffer ?

• Buffer capacity is highest at a pH near the pKa and drops significantly more than 1 pH unit away from it.

• To create a buffer effective over a wide pH range, a mixture of acids with different pKa values (polybasic and monobasic acids) is used. Such mixtures are called universal buffers.

• Universal buffers solve this by mixing several acids with different pKa values.
  How ?

• Each acid in the mix has a different pKa. Each acid can buffer (control pH) best near its own pKa. By combining acids with different pKa values, the solution can buffer across a wider pH range.
  

What are examples of some universal buffers ?

This combination means the solution resists pH changes effectively from ~ pH 2.4 to 12
i.e much wider than a single buffer could handle

summary

• Buffers are made from a weak acid and its salt, or a weak base and its salt

• You can calculate the pH of a buffer using the Henderson–Hasselbalch equation

• Buffers work best at a pH near the weak acid’s pKa, where their ability to resist pH changes (buffer capacity) is highest

• Buffers are vital for medicine (e.g formulation for I.V use, eye drops, Nasal sprays