UNIT 5:
PH, BUFFER AND BUFFERED ISOTONIC
SOLUTION
Dr. Abdikarim M. Mohamoud (Guudcade)
MPH in Epidemiology, P. G Research methodology and Data Analysis, BDVM and
diploma laboratory science
5.1 INTRODUCTION:
1. pH:
pH is the negative logarithm of hydrogen ion concentration [ 𝐻+] in a
solution.
It indicates how acidic or basic a solution is.
Acids and Bases:
♠ Acids are substances that donate hydrogen ions (H ⁺) to a solution.
♠ Example: HCl → H⁺ + Cl⁻
♠ Bases are substances that accept hydrogen ions (H ⁺) or produce
hydroxyl ions (OH⁻).
♠ Example: NaOH → Na⁺ + OH⁻
IONIC REACTIONS AND THE LAW OF MASS ACTION:
♠ An Ionic Reactions is a chemical reaction that occurs between ions in
an aqueous solution.
♠ These reactions usually involve the exchange of ions to form new
products such as precipitates, water, or gases.
♠ Example: 𝐻𝐶𝑙(𝑎𝑞) + 𝑁𝑎𝑂𝐻(𝑎𝑞) → 𝑁𝑎𝐶𝑙(𝑎𝑞)+𝐻2𝑂(𝑙).
(Acid-base neutralization reaction between hydrogen ions and hydroxyl
ions).
♠ Law of Mass Action is the states that the rate of a chemical reaction is
directly proportional to the product of the concentrations of the reactants, each
raised to the power of their stoichiometric coefficients.
♠ Example: 2𝐻2+𝑂2 → 2𝐻2𝑂
♠ In the case of weak acid dissociation:
𝐻𝐴 ⇌ 𝐻++𝐴−
♠ The equilibrium constant expression is:
𝐾𝑎= [𝐻+] [𝐴−]
♠ Dissociation Constant (Ka): A measure of the strength of an acid in
solution.
o High Ka → Strong acid (dissociates more).
o Low Ka → Weak acid (dissociates less).
♠ Hydrogen Ion Concentration [𝐻+] is The molar concentration of
hydrogen ions in a solution, expressed in mol/L.
♠ Hydroxyl Ion Concentration [𝑂𝐻−] is the molar concentration of hydroxyl
ions in a solution, expressed in mol/L.
♠ pH: is a scale used to measure the acidity or alkalinity of a solution, defined
as:
o pH =−log[H+]
• Low pH (<7) = acidic
• pH = 7 = neutral
• High pH (>7) = basic
Examples of pH Values:
o Stomach acid → pH 1–2 (strongly acidic).
o Pure water → pH 7 (neutral).
o Blood plasma → pH 7.35–7.45 (slightly alkaline).
o Soap solution → pH 9–10 (alkaline).
5.2 SORENSEN’S pH SCALE:
Sorensen’s pH scale is introduced by Danish biochemist Søren Peter
Lauritz Sørensen in 1909, is a logarithmic scale used to measure the
acidity or alkalinity of an aqueous solution.
Every aqueous solution contains hydrogen ions (H ⁺), and their
concentration is a key factor in describing the properties of a solution.
Origin of the Term “pH”:
o pH = “pondus hydrogenii” (Latin for potential of hydrogen) or power of
hydrogen.
o The “p” comes from German Potenz = power.
o written as “PH”
pH refers to potential of hydrogen ions concentration.
Sorenson's has defined pH of a solution as the logarithm of the
reciprocal of the hydrogen ions or hydronium ions concentration [H30+].
Mathematical Expression of pH:
o Sorensen defined pH as the logarithm of the reciprocal of hydrogen ion
concentration.
1. Definition:
o 𝑝𝐻 = log1 ............................................................................(1)
[𝐻+]
2. Applying log rule:
o log1 = log1 − log[𝐻+]
[𝐻+]
o 𝑝𝐻 = log1 − log [𝐻+] …………………………………………..(2)
3. Since log1=0
o 𝑝𝐻 = 0 − log [𝐻+]
o 𝑝𝐻 = −log[𝐻+] …………………………………………..(3)
Final Formula:
o pH = −log [H+]
This means pH is the negative logarithm of hydrogen ion concentration,
expressed in mol/L.
Example: If [𝐻+]=1×10−7 𝑀
o then: 𝑝𝐻 = −log(1×10−7) =7
o So, pure water has a neutral pH of 7.
Acidic and Basic Solutions According to Sorensen’s pH Scale:
1. Acidic solutions:
o Solutions having [H⁺] > 1 × 10⁻⁷ M are acidic.
o Their pH < 7.
o Example: Gastric juice (pH ≈ 1–2).
2. Basic (alkaline) solutions:
o Solutions having [H⁺] < 1 × 10⁻⁷ M are basic.
oTheir pH > 7.
o Example: Soap solution (pH ≈ 9–10).
[Link] solution:
o When [H⁺] = [OH⁻] = 1 × 10⁻⁷ M,
o pH = 7, such as pure water at 25°C.
Applications of pH Control in Pharmacy:
Controlling pH is essential in the preparation, stability, and activity of
pharmaceutical products such as eye drops, ear drops, injections, and oral
liquids.
1. Enhancing Solubility and Stability:
o The pH of pharmaceutical preparations must be adjusted so that the active
pharmaceutical ingredient (API) remains soluble and physically stable.
o Example: Some weakly acidic or basic drugs dissolve better at specific pH
ranges.
2. Absorption of Drugs:
oThe gastrointestinal tract (GIT) has varying pH levels in different regions.
o Drug molecules are absorbed differently depending on the local pH.
o Example: Weakly basic drugs absorb better in the intestine (alkaline pH),
while weak acids absorb better in the stomach (acidic pH).
3. Storage of Products:
oGlass containers may impart alkalinity and alter the pH of the stored
product.
o Adjusting pH ensures the stability and safety of drugs during storage.
4. Comforting the Body:
o Pharmaceutical formulations administered to the body must have an
optimum pH to avoid harmful effects.
• Eye drops: should not cause irritation.
• Injections: must not cause haemolysis (destruction of red blood cells).
• Topical solutions: must not cause burning on abraded skin.
pH DETERMINATION:
The are two widely accepted methods for the determination of the pH of a
solution, which are:
1. Colorimetric method.
2. Electrometric method.
1. Colorimetric method:
o Colorimetric method is a simple way of finding the pH of a solution by
matching its color (after adding an indicator) with standard colors of known pH.
Principle:
o Based on colour comparison of the test solution with that of standard
solutions, both treated with a universal indicator.
oThe universal indicator produces different colours depending on the pH of
the solution.
oThe method is useful for measuring pH in the range of 3 to 11.
Indicators Used:
oIndicator strips (pH papers):
• Filter paper impregnated with universal indicator is used to directly identify
approximate pH by comparing colours with a chart.
oStandard solutions:
• Prepared by mixing buffer solutions with universal indicators.
Advantages
• Less expensive.
• Easy estimation of pH unless the drug shows buffer action.
Disadvantage:
• This method is less accurate and less convenient.
• It is not useful for coloured or turbid solution.
2. Electrometric Method:
o A method of determining the pH of a solution by measuring the electrical
potential (voltage) between special electrodes placed in the solution.
Principle:
o The potential difference between the glass electrode and the solution
depends on the hydrogen ion concentration.
oThis variation in voltage is directly related to the pH of the solution.
o Common electrodes: Glass electrode and Hydrogen electrode. The
instrument used is the pH meter.
Note: This method is more accurate than the colorimetric method and can
measure pH outside the 3–11 range.
Advantages:
• It gives an accurate measurement of pH.
• Glass electrode is not affected by oxidation-reduction system.
• The electrode establishes equilibrium rapidly.
• The indicator need not required.
Disadvantages:
• The cost of pH meter is high compared to colorimetric method.
• This method is not suitable for viscous solutions and gels because of poor
ionic mobility.
INDICATORS:
o A pH indicator is a weak acid or weak base that changes color depending on
the pH of the solution. This helps to determine whether a solution is acidic,
neutral, or basic.
othe color of the indicator depends on the hydrogen ion concentration
[H⁺].
oCommon indicators: Phenolphthalein, Methyl red, and Thymol blue.
Universal Indicator:
A mixture of several indicators.
oProvides a wide range of color changes for different pH values (pH 1–11).
oUseful for estimating the approximate pH of a solution.
Examples of Indicators and Their pH Ranges:
Indicator pH Range Color Change
Methyl yellow 3.1 – 4.4 Red → Yellow
Methyl red 4.2 – 6.2 Red → Yellow
Bromothymol blue 6.0 – 7.6 Yellow → Blue
Thymol blue 8.0 – 9.6 Yellow → Blue
Phenolphthalein 8.3 – 10.0 Colorless → Pink
Universal indicator 1.0 – 11.0 Multiple color changes
BUFFER:
A buffer is a solution (or mixture of compounds) that resists a change in
pH when small amounts of acid or base are added.
o Buffer action: The resistance to pH change.
o Buffer capacity (B): The amount of acid/base required to change the pH
of 1 liter of buffer solution by 1 unit.
BUFFER EQUATION:
For a weak acid and its salt Terms stands for:
o pH: measure of hydrogen ion concentration
(acidity/basicity).
For a weak base and its salt: o pKa: the negative logarithm of the acid
dissociation constant (Ka) of the weak acid. It
tells how strong/weak the acid.
o [Salt]: concentration of the conjugate base
(salt of the weak acid).
o [Acid]: concentration of the weak acid.
APPLICATIONS OF BUFFERS IN PHARMACY:
Solubility enhancement: Maintain drugs in soluble form during shelf-life.
Stability: Prevent hydrolysis and degradation.
Purity: Protein solubility is lowest at isoelectric point (used to identify
purity).
Biological activity: Enzymes function best at specific pH values.
Comfort & safety: Adjust pH of eye drops, injections, and oral liquids to
avoid irritation or hemolysis.
Storage: Prevent glass containers from altering pH of formulations.
Buffer Capacity:
oThe ability of a buffer solution to resist changes in pH when small amounts
of acid or base are added.
• Greatest when [salt] = [acid].
• Not fixed, depends on concentration and ratio of salt/acid.
• High capacity = better resistance to pH change.
Pharmaceutical Buffers:
o Buffer solutions specially prepared and used in medicines and drug
formulations to maintain the required pH for stability, solubility, and
effectiveness of the drug.
Ophthalmic Solutions:
oThese are sterile liquid preparations intended for direct application to the eye.
They must be free from particles, have suitable pH and tonicity (close to that
of natural tears), and often use buffers (like borate or phosphate buffers) to
o Example: Eye drops such as artificial tears, antibiotic drops, or anti-allergy
drops.
Biological Buffer Systems:
o Biological buffer systems are natural buffer solutions present in the body
that help maintain a stable pH, which is essential for proper cellular and
biochemical functions.
oThey prevent harmful changes in hydrogen ion concentration when acids or
o Examples include:
• Bicarbonate buffer system: regulates blood pH (~7.4).
• Phosphate buffer system: maintains pH in intracellular fluids.
• Protein buffer system (e.g., hemoglobin in blood): buffers both acids and
bases.
BUFFERED ISOTONIC SOLUTION:
o A buffered isotonic solution is a solution that maintains the same osmotic
pressure (isotonicity) and pH as body fluids, such as blood and tears.
o It prevents irritation, haemolysis, and tissue damage when applied to
delicate membranes.
Applications of Buffered Isotonic Solutions:
o The application of buffered isotonic solutions including the following:
1. Used for injections and infusions must match blood plasma (e.g., IV
infusions and subcutaneous).
2. Used for eye drops must match tears to avoid irritation.
3. Used to prevent burning or irritation.
4. Used for washing of wounds and tissues.
Preparation Steps:
oThe preparation of steps including the following:
1. dissolve drug + ingredients in water.
2. Measure and adjust pH.
3. Calculate tonicity value.
4. Add required NaCl (or equivalent) to adjust tonicity.
5. Add isotonic diluting solution to maintain drug dose.
6. If pH also needs adjusting → use buffered isotonic diluting solution.
o Examples of isotonic diluting solutions:
0.9% NaCl (normal saline).
5% Dextrose.
Ringer’s solution.
Types of Solutions:
o There are three types of solution, which are:
1. Isotonic Solution:
o A solution that has the same osmotic pressure as body fluids or cells, so
there is no net movement of water across the cell membrane.
o Safe for use with body tissues.
o Examples: 0.9% Sodium chloride (normal saline),and 5% Dextrose.
2. Hypertonic Solution:
o A solution with a higher solute concentration than body fluids.
o Causes cells to lose water and shrink (crenation).
o Examples: 2% Sodium chloride and 10% Dextrose.
3. Hypotonic Solution:
o A solution with a lower solute concentration than body fluids.
o Causes cells to take in water, swell, and possibly burst (hemolysis).
o Examples: 0.2% Sodium chloride and Distilled water.