Arrhenius theory

Bronsted Lowry Theory

Acid Acid

Base Base
 Bronsted Lowry Theory
Conjugate acid-base pair

one with H/H+ (acid) and without H/H+ (base)

Acid Conjugate base Acid Conjugate base

 Bronsted Lowry Theory

Strong Acid Weak Weak

Strong Base
Conjugate base Conjugate acid
Acid dissociation
Base dissociation
Water auto-ionisation

At 100°C, a pH value of 6.14 is the New neutral

point on the pH scale
Water auto-ionisation
pH
pOH
pH Scale
Relation between pH & pOH
Weak acids and bases

– log Ka – log Kb = – log Kw = – log 10-14

 Buffers
Buffer Solution : The solution which resist change in pH upon addition of small amount of acid or alkali
are called buffer solutions.

1. Acidic Buffer : It is combination of weak acid & its corresponding salt. E.g.

2. Basic Buffer: It is combination of weak base and its corresponding salt.

3. Neutral Buffer: It is single substance showing the properties of buffer.

e.g. ammonium acetate.

 Buffers action
Buffer Solution : Ability of solution to resist change in their pH upon addition of a acid or
a base is called as buffer action

1. Mechanism of buffer action of Acidic Buffer : e.g. Acetic acid + Sodium acetate.

2. Mechanism of buffer action of Basic Buffer : e.g. Ammonium hydroxide + Ammonium chloride

3. Mechanism of buffer action of Neutral Buffer : e.g. Ammonium acetate

Henderson Hasselbalch equation for acidic buffer
According to Henderson-Hasselbach
equation,
when the concentrations of the acid (HA)
and the conjugate base (A-) are the same,
i.e, when the acid is 50% dissociated, pH of
the solution is equal to the pKa of the acid.
Henderson Hasselbalch equation for acidic buffer
What is the pH of a buffer solution with concentrations of 0.2 M CH3COOH and 0.5 M CH3COO- .
The acid dissociation constant For CH3COOH is 1.8 × 10-5
Henderson Hasselbalch equation for acidic buffer
What is the pH of a buffer solution with concentrations of 0.2 M CH3COOH and 0.5 M CH3COO- .
The acid dissociation constant For CH3COOH is 1.8 × 10-5
Henderson Hasselbalch equation for basic buffer

NaOH Na+ + OH- NH3 + H2O NH4+ + OH-

 Acidic buffer pH range
Acid conjugate
base

• When, [conjugate base]: [Acid] = 1 : 1 , pH = pKa of acid

• When, [conjugate base]: [Acid] = 10 : 1, pH = pKa + 1
• When, [conjugate base]: [Acid] = 1 : 10, pH = pKa – 1

• Buffers are only effective when pH is within 1 unit from the pKa i.e. pKa ± 1

• Buffers are most effective when pH of buffer system is equal to the pKa of acid

• When designing buffer, the pKa of acid should be as close to the desired pH.
e.g. for making buffer of pH=7.4, options would be
1. HClO/NaClO pKa =7.40 (buffer range of 6.40 to 8.40)
2. NaH2PO4/Na2HPO4 pKa = 7.21 (buffer range of 6.21 to 8.21)
 Buffer capacity
• Buffer capacity also referred as buffer index, buffer value, buffer efficiency or buffer coefficient

• Definition : The amount of acid of base that must be added to the buffer to produce a unit change of pH.

β = Δ[AH/B] / Δ pH
• Buffer capacity is maximum when pH = pKa
1.1 Acetic acid pka 4.76

0.8

0.2

Plot of Buffer capacity vs pH of the acetic acid / sodium acetate buffer system
 Effect of [A-]/[HA] on buffer capacity
Acid – HA , Salt – A-
Acid Pka = 7.2

Five buffers with different [A-]/[HA] mEq (mM)

1. 10/190 (pH = 5.929)

2. 50/150 (pH 6.731)
3. 100/100 (pH = 7.2)
4. 150/50 (pH = 7.685)
5. 190/10 (pH = 8.487)

• Buffer 3 has maximum buffer capacity

• Buffer capacity is maximum when pH = pKa
• OR when concentration of [A-] and [HA] are same
Effect of Individual concentration of A- and HA on buffer capacity
Two buffers with different [A-] and [HA] in mEq (mM)

1. 100 mM /100 mM (pH = 7.2)

2. 1000 mM /1000 mM (pH = 7.2)

• Buffer 2 has maximum buffer capacity

• Buffer capacity is maximum concentration of [A-] and [HA] is more
• Rule of thumb is, for buffer preparation concentration of [A -] and [HA] should be between 0.1 to 1 M
 Pharmaceutical Buffer Selection
Chemical aspects

1. The buffer should not react with other chemicals in the preparation.
2. Buffer pair should not participate oxidation-reduction reactions
3. It should not alter the solubility of other components
4. It should not form complexes with active ingredients
5. The buffer system itself must also exhibit reasonable chemical stability
6. Volatile species e.g. NH3 and CO2 should be avoided as their loss will alter pH and buffer capacity of the system
7. Alkaline buffers should be protected against the absorption of CO 2 from the air which would ultimately produce
a drop in the pH.

Pharmacological aspects

8. Buffer should neither contribute nor detract from the pharmacological properties of the active ingredient
9. Borate buffers are toxic when administered systemically. These must be reserved for topical preparations
10. Buffer, particularly when the pH is close to neutrality serves as nutrient media for certain microorganisms.
Solutions of these compound can be preserved with low concentration of antimicrobial agents
 Role of Pharmaceutical Buffers
Solubility
1. Precipitation of salts of Fe, phosphates and borates precipitate in alkaline media e.g. Fe as Fe(OH) 2
2. Amines and alkaloids are soluble in acidic media but insoluble in alkaline media

Colour
3. Colour of many natural dyes has been found to be pH dependent e.g. red colour of cherry and raspberry syrups has been
maintained at acidic pH which becomes pale yellow to colourless at alkaline pH
4. The colour of synthetic compounds like phenolphthalein are also pH dependent

Stability
5. Degradation of ascorbic acid and penicillin is pH dependent
6. Sodium thoisulphate and sodium polysulphide preparations need to be stored in alkaline condition to prevent separation of
sulphur
7. Nitrites become brown in acid media because of formation of coloured nitrogen oxides

Patient comfort
8. Injectable and preparations for local use become irritating if their pH is different greatly for that of normal for that particular
tissue
 Buffers in pharmaceutical systems
A. Buffers used to provide a specific pH for analytical purposes
B. Buffers used to maintain pH in drug preparations

A. Buffers used to provide a specific pH for analytical purposes (Standard Buffers)

• Use of standard buffers

• reference purposes in pH measurements
• carrying out many pharmacopoeial tests

• Properties of standard buffers

• Standard Buffer Solutions are solutions have standard pH values between 1.2 to 10.0
• pH values are these buffers are reproducible within ± 0.02 Unit at 25°.

• Precautions to be taken during preparation of Standard Buffers

1. All the crystalline reagents except boric acid should be dried at 110° to 120° for 1 hour before use.
2. Carbon dioxide-free water should be used for preparing buffer solutions
3. The prepared solutions should be stored in chemically resistant, glass-stoppered bottles of alkali-free glass
4. Prepared buffer should be used within 3 months of preparation.
5. Solution which has become cloudy or shows evidence of deterioration should be discarded.
 Buffers in pharmaceutical systems
A. Buffers used to provide a specific pH for analytical purposes (Standard Buffers)

• Names of standard buffers

1. Hydrochloric Acid Buffer
2. Acid Phthalate Buffer
3. Neutralised Phthalate Buffer/Phthalate Buffer
4. Phosphate Buffer
5. Alkaline Borate Buffer

• Preparation of standard buffers

• Standard buffer solutions are prepared by appropriate combinations of 0.2 M HCl or 0.2 M NaOH and
0.2 M solutions of either of :
• Potassium Chloride
• Potassium Chloride and Boric Acid
• Potassium Dihydrogen Phosphate
• Disodium Hydrogen Phosphate
• Potassium Hydrogen Phthalate
 Standard Buffer Solutions (composition)
Sr.
Buffer name pH range Composition
No.

To 50 ml of 0.2M potassium chloride add specified volume of 0.2 M hydrochloric

1 Hydrochloric Acid Buffer 1.2 – 2.2
acid and then add water to make 200 ml

To 50.0 ml of 0.2 M potassium hydrogen phthalate add specified volume of 0.2 M

2 Acid Phthalate Buffer 2.2 – 4.0 hydrochloric acid then add water to make 200 ml

Neutralised Phthalate Buffer; To 50.0 ml of 0.2 M potassium hydrogen phthalate add specified volume of 0.2 M
3 4.2 – 5.8
Phthalate Buffer sodium hydroxide then add water to make 200 ml

To 50.0 ml of 0.2 M potassium dihydrogen phosphate add specified volume of 0.2 M

4 Phosphate Buffer 5.8 – 8.0 sodium hydroxide then add water to make 200 ml

To 50.0 ml of 0.2 M boric acid and potassium chloride in add specified volume of 0.2
5 Alkaline Borate Buffer 8.0 – 10.0 M sodium hydroxide then add water to make 200 ml
Standard Buffer Solutions (composition)
Preparation of Buffer components
 Buffer Solutions
A. Buffers used to maintain pH in drug preparations

• PHOSPHATE BUFFER SYSTEM

• ADVANTAGES
• It is compatible physiologically.
• The pKa of dihydrogen phosphate anion is 7.2 making this very efficient buffer system at pH of physiological
fluid including lachrymal fluid
• DISTADVANTAGES
• Cations such as Ag, Al, Zn are insoluble in the phosphate buffer. Therefore they can not be used in preparation
containing zinc salts
• It precipitate calcium, iron and magnesium if taken internally
• Phosphate buffer allows mold growth at room temperature and requires antifungal agent for preservation
• BORATE BUFFER SYSTEM
• ADVANTAGES
• They are used as alternative to phosphate buffers in preparation containing metals
• DISADVATAGES
• Boric acid and borate are toxic if taken internally
• The pKa of boric acid is 9.2, making this system inefficient at physiological pH.
• Borates are weak bacteriostatic, still support the mold growth at room temperature