PHYSICAL PHARMACY Report - pH and Buffers.pptx

pH and
Buffer
A PHYSICAL PHARMACY
PRESENTATION

Hi! Di Kita
Durogen:
A GENERAL GUIDE TO HYDROGEN
TERMS

ELECTROLYTES
VS
NONELECTROLYTE
S

What is an Electrolyte?
An electrolyte is a substance that in an aqueous
solution ionizes to positive ions and negative ions
Salts such as sodium chloride (NaCl) is an example of
an Electrolyte

TWO GROUPS OF
ELECTROLYTES
Depending on their ability to ionize in an aqueous
solution electrolytes can be classified as :

What is a Nonelectrolyte
Nonelectrolytes are substances that do not ionize in
water at all and therefore do not conduct an electric
current in solution. Examples of nonelectrolytes include
sucrose, fructose, urea, and glycerol.

What’s The Difference?
Electrolyte Nonelectrolyte
Electrolytes are chemical
compounds that can break
down into ions when
dissolved in water
Can conduct electricity
Composed of ionic bonds
Include acids, base and salts
DISSOLVED
IN WATER
Nonelectrolytes are chemical
compounds whose aqueous
solutions cannot conduct electricity
through the solution
Cannot conduct electricity through
their aqueous solution
Composed of covalent bonds
Include carbon-containing
compounds, fat and sugar

PRODUCT SHARAWT
POCARI SWEAT is a health drink that
contains a balance of ions (electrolytes)
that resembles the natural fluid balance
in the human body. Quickly and easily
replenishes the water and ions that your
body needs
A Product of Otsuka Pharmaceuticals
based in Japan

ACIDS AND BASES
In chemistry there are three primary theories of acid-
base that are often taught together; Arrhenius Theory,
Brønsted-Lowry theory and Lewis acid-base theory.
(7.1A: Acid-Base Theories and Concepts, 2017).

Arrhenius Theory
The first theory was proposed by Arrhenius in 1884.
According to Arrhenius an acid is a substance that produces
hydrogen ion (H+) in aqueous solution, whereas a base
produces hydroxyl ions (OH-) in same solution.
The opposite nature of their characters is emphasized.
There is no account for their behavior in non aqueous media.

Brønsted-Lowry Theory
In 1923, Brønsted-Lowry defined an
acid as a species with a tendency to
lose a proton, whereas a base has a
tendency to accept a proton.
The greater the tendency of a
substance to lose a proton, the
stronger that substance is as an acid.
Conjugated acid-base pair refers to a
pair of substances related by loss or
gain of a proton.

The stronger an acid, the weaker its conjugate base, and vice versa.

Lewis Electronic Theory
In 1923, G.N. Lewis introduced a new theory of acids and bases.
An acid is a molecule or ion that accepts an electron pair to form a
covalent bond. A base is defined as a substance that provides the pair
of unshared electrons by which the base coordinates with an acid.
According to this definition, some species that do not contain a
hydrogen can be considered acids.

REFERENCE
7.1A: Acid-Base Theories and Concepts. (2017, June 3).
Chemistry LibreTexts.
https://chem.libretexts.org/Bookshelves/Inorganic_Chemistry/Ma
p%3A_Inorganic_Chemistry_(Housecroft)/07%3A_Acids_bases
_and_ions_in_aqueous_solution/7.01%3A_Introduction/7.1A%3
A_Acid-
Base_Theories_and_Concepts#:~:text=There%20are%20three
%20primary%20theories

What is Ionization?
Ionization is defined as the process by which an atom or
molecule gains or loses a positive or negative charge as a
result of chemical changes.
An ion is an electrically charged atom or molecule that results.
 Anion - an ion that has a negative charge
 Cation - an ion that has a positive charge

Water acts either as an acid or a base.
•When one molecule react with another to form
hydronium ion H3O+ and hydroxyl ion OH− ion this
process called auto-ionization or self-ionization.

Ionization Constant for Water
Where: Kw = Ionization constant
for water.
In pure water at 25 ℃, The
concentration of hydronium ion and
hydroxyl ion is equal at equilibrium
between water and (hydronium,
hydroxyl) ions.
[H3O+] = 1× 10 -7 mol/L
[OH-] = 1× 10 -7 mol/L

For example, if we add 1.00 mol of the strong acid HNO3 to
H2O to make a total volume of 1 L, essentially all the HNO3
molecules donate their protons to H2O: and a solution in which
[H3O+] = 1.00 mol/L is obtained.

Although this solution is very acidic, there are still hydroxide ions
present. We can calculate their concentration by rearranging Eq.
Formula:
Solution:

Relationship Between pKa and
pKb
Ka and Kb are related to each other through the ion constant
for water, Kw:
Kw = Ka x Kb
Ka and pKa relate to acids, while Kb and pKb deal with bases.
• Ka = is the acid dissociation constant.
• pKa = is simply the -log of this constant.
• Kb = is the base dissociation constant
• pKb = is the -log of the constant.

pKb
> A large Ka value indicates a strong
acid because it means the acid is
largely dissociated into its ions.
> A large Ka value also means the
formation of products in the reaction
is favored.
> A small Ka value means little of the
acid dissociates, so you have a weak
acid.
> The Ka value for most weak acids
ranges from 10-2 to 10-14.

pKb
The pKa gives the same information, just in a different way. The
smaller the value of pKa, the stronger the acid. Weak acids have a
pKa ranging from 2-14.

REFERENCES
https://chem.libretexts.org/Bookshelves/General_Chemistry/Che
mPRIME_(Moore_et_al.)/14%3A_Ionic_Equilibria_in_Aqueous_
Solutions/14.02%3A_Ionization_of_Water
https://byjus.com/chemistry/ionization-of-water/

Strong Acids and Strong
Bases
• defined as those that are completely ionized at all pH
values
• their extent of ionization is pH-independent
• Hydrochloric acid in water is considered a strong acid
• The conjugate acid 𝐶𝑙− is very weak

Weak Acids
• are incompletely ionized at some pH values
• extent of ionization is pH-dependent
Phenol in the presence of water.
• Weak tendency to ionize, and the conjugate base,
phenoxide ion, is moderately strong

Organic Weak Acids
The organic weak acid HA dissolves in water with the
following ionization equilibrium
The concentration of water is generally omitted from this
equilibrium for simplicity.
or

At equilibrium, rate 1 = rate 2 or
- The ratio is called the acidic ionization constant 𝐾_𝑎.
- In the absence of any common ion in solution, one should
expect the [𝐻^+] to be equal to [𝐴^−]. Ionization constant can be
expressed as :

If the ionization of the acid is very low, one can substitute the
total concentration of the acid (C) equal to [HA].
Taking the (-log) on both sides:
The ratio of ionized form to unionized form of the drug in fluids
may be calculated as
where 𝐴^− is the conjugate base

Calculate the pH of a 0.1 M solution of a weak acid at
25°C (77 °F). The 𝑝𝐾𝑎 of the acid is 4.76 at 25°C (77
°F).
Example

Salicylic acid is an organic weak acid with a 𝑝𝐾𝑎 of 3.0.
Calculate the ratio of ionized form to the unionized form
of this drug in the stomach with the pH 1.2.
A. For weakly acidic drug, use the equation
Example
[𝐴−
]
[𝐻𝐴]
= 10(1.2−3)
[𝐴−]
[𝐻𝐴]
= 0.016
Therefore, the ratio of
ionized to unionized salicylic
acid will be 0.016/1.

What will be the ratio of ionized to unionized form of a
weak acid if the pH of the solution is 6 and pKa is 3?
Example
[𝐴−
]
[𝐻𝐴]
= 10(𝑝𝐻−𝑝𝐾𝑎)
[𝐴−
]
[𝐻𝐴]
= 10(6−3)
[𝐴−]
[𝐻𝐴]
= 1000
Therefore, the ratio of ionized to
unionized of a weak acid is 1000/1.

Organic Weak Bases
Weak bases can be defined
as basic substances that do
not completely dissociate into
their constituent ions when
dissolved in solutions.
When a weak base is
dissolved in water, the
following type of equilibrium
arises:

Organic Weak Bases
The pH of the protonated organic weak base can be
calculated from this formula.
The pH of the organic weak base (free base) in water can be
calculated by using pKa pKw, and the concentration of the
base [B], or C, as given here:

Values for Kb, pKb, and pKa for a weak base

Calculate the pH of a 0.1 M solution of a weak base
(trimethylamine) at 25°C (77°F).
Example

Caffeine, C8H10N4O2 is a weak base. What is the
value of Kb for caffeine if a solution at equilibrium has
[C8H10N4O2] = 0.050 M, [C8H10N4O2H+] = 5.0 ×
10−3 M, and [OH–] = 2.5 × 10−3 M?
Example

A salt is formed by an acid-base reaction involving
either a proton donation or a proton acceptance.
Salts can be classified into the following four
categories:
1. Salts of strong acids and strong bases
2. Salts of weak acids and strong bases
3. Salts of strong acids and weak bases
4. Salts of weak acids and weak bases
IONIZATION OF SALTS

Salts of this class do not undergo hydrolysis; therefore,
the concentrations of hydrogen and hydroxyl ions
remain unchanged.
The salt solution in water therefore shows a neutral
reaction.
An example of this class is Sodium Chloride
Salts of Strong Acids and Strong
Bases

Salts of Strong Acids and Strong
Bases

Salts of this category completely ionize in aqueous
solution, and the hydrolysis reaction results in a basic
solution:
The conjugate anion A− interacts with water to form the
molecular acid and hydroxide ion, resulting in an
alkaline solution:
Salts of Weak Acids and Strong
Bases

Bases

Bases
WHERE:
pKw is the negative base-10 logarithm of the ion product of water. At 25°C, the
value of pKw is approximately 14. The half of which is 7

Have an acidic pH in water.
When a salt of a weak base and a strong acid is added
to water, it is completely ionized in the aqueous
solution.
Salts of Strong Acids and Weak
Bases

Have a basic pH in water.
Salts of this category completely ionize in aqueous
solution, and the hydrolysis reaction results in a basic
solution:
bases

The main purpose of formulating a drug in its salt form
is that, being already ionized, the salt form has greater
water solubility than its free acid or free base
counterpart.
The hydrolysis reaction is like Ka
Salts of Strong Acids and Weak
Bases

1. To calculate the pH of 0.1 M ephedrine
hydrochloride in water, pKa = 9.36:
pH= ½ pKa - ½ log C
=½ (9.36)- ½ log (0.1)
=4.68 + 0.5
= 5.2
Example

2. A solution contains acetic acid (CH3COOH) at
a concentration of 0.10 M. The pKa of acetic acid
is 4.76. Calculate the pH of the solution.
pH= ½ pKa - ½ log C
= ½ (4.76) - ½ log (0.10)
= 2.38 + 0.5
pH= 2.88
Example

BUFFERS
A solution containing either a weak acid with its conjugate base
or a weak base with its conjugate acid has the capacity to
function as a buffer.
It protects the formulation from a sudden change in pH.
Acts by neutralizing any hydrogen ions or hydroxyl ions added to
it.
HA + OH- → A- + H2O
A- + H3O+ → HA + OH

The Buffer Equation
The Henderson-Hasselbalch equation or the buffer equation,
also can be used to calculate the pH of a buffer solution:

1. Calculate the pH of the buffer solution if the
molar concentration of phenobarbital is 0.03 M
and that of sodium phenobarbital is 0.02 M. The
pKa for phenobarbital is 7.4.
pH = 7.4 + log(0.02)/(0.03)
= 7.4 + (-0.18)
= 7.2
Example

2. Calculate the pH of a buffer solution made
from 0.20 M HC2H3O2 and 0.50 M C2H3O2-
that has an acid dissociation constant for
HC2H3O2 of 1.8 x 10-5.
pH = pKa + log ([A-]/[HA])
= pKa + log ([C2H3O2-] / [HC2H3O2])
= -log (1.8 x 10-5) + log (0.50 M / 0.20 M)
= -log (1.8 x 10-5) + log (2.5)
= 4.7 + 0.40
Example

Buffers are characterized by the pH range over
which they can maintain a more or less constant
pH and by their buffer capacity, the amount of
strong acid or base that can be absorbed before
the pH changes significantly. Although the useful
pH range of a buffer depends strongly on the
chemical properties of the weak acid and weak
base used to prepare the buffer
Buffer Capacity and Preparations of
Buffer

Buffer solutions do not have an unlimited
capacity to keep the pH relatively constant If we
add so much base to a buffer that the weak acid
is exhausted, no more buffering action toward
the base is possible. On the other hand, if we
add an excess of acid, the weak base would be
exhausted, and no more buffering action toward
any additional acid would be possible.
Buffer Capacity

In fact, we do not even need to exhaust all of the
acid or base in a buffer to overwhelm it; its
buffering action will diminish rapidly as a given
component nears depletion.`

Should have about equal concentrations of both
of its components. a buffer solution has generally
lost its usefulness when one component of the
buffer pair is less than about 10% of the other.
A buffer that contains approximately equal
amounts of a weak acid and its conjugate base
in solution is equally effective at neutralizing
either added base or added acid.
A GOOD BUFFER MIXTURE

In many situations, chemists must prepare buffer
solutions to maintain a desired pH. There are many
different buffer systems to choose from, depending on
the characteristics and pH required of the solution. The
following steps may be used when preparing a buffer in
the laboratory:
PREPARING BUFFER

1. Choose an appropriate buffer system. Because the buffer
capacity is highest where pH = pKa, the ideal buffer will have
a pKa close to the desired pH. In general, weak acids and their
salts are better as buffers for pHs less than 7; weak bases and
their salts are better as buffers for pHs greater than 7.
2. Use the total buffer concentration and pH desired to
calculate the amounts of acid and base needed to create the
buffer. The Henderson-Hasselbalch equation can be used to
determine the ratio of [base]/[acid] needed.
PREPARING BUFFER

Calculate the pH of a buffer (weak acid) containing 0.1M
sodium acetate (CH3COOH) and 0.2 M acetic
acid(CH3COONa) (pKa=4.76)
pH = pKa + log base/acid
EXAMPLE

IONIZATION OF
AMPHOTERIC
ELECTROLYTES

What are ampholytes?
• are amphoteric molecules that exist primarily as
zwitterions over a given pH range and have both
acidic groups and basic groups.
• in techniques like isoelectric focusing.
• from Greek “amphi-” meaning “both”) is a molecule or
ion that can react as both an acid and a base.
Definition:

AMPHOTERIC
ELECTROLYTES
• “of acting as acids towards bases and as bases
towards acids. One of the simplest types is that of the
amino-acids, for example, glycine, NH2.CH2.COOH,
which in virtue of the NH2 group is an anhydrous
base, whilst in virtue of the COOH group it is an
ordinary organic acid.

SOME EXAMPLES OF
AMPHOTERISM
These metal oxides react with both acids and bases to
produce salts and water.
Examples include:
aluminium oxide (Al2O3).
Other metals like zinc, tin, lead, and beryllium.
Amphoteric Oxides:

SOME EXAMPLES OF
AMPHOTERISM
They can either donate or accept a proton (H+).
Examples include amino acids and proteins, which
have both amine (−NH2) and carboxylic acid (−COOH)
groups.
Water itself is also amphiprotic
Amphoteric Molecules:

IN SUMMARY
Amphoteric compounds are versatile
players in the chemical orchestra,
dancing between acidity and basicity!

IONIZATION OF
POLYPROTIC
ACIDS

Polyprotic acid
• An acid that contains more than one ionizable proton
• vary by roughly five orders of magnitude.
• are Bronsted-Lowry acids that can donate more than
one proton.

Some examples of
polyprotic acids are:
• H 2S (hydrogen sulfide)
• H 2SO 4 (sulfuric acid)
• H 3PO 4 (phosphoric acid)
• C 10 H 16 N 2 O 8 (Ethylenediaminetetraacetic acid,
or EDTA)

SPECIFIC TYPES OF
POLYPROTIC
• Diprotic and Triprotic are specific types of polyprotic
acid capable of donating two and three protons,
respectively.

SPECIFIC TYPES OF
POLYPROTIC
• diprotic acid - acid containing two ionizable hydrogen
atoms per molecule.
• diprotic base - base capable of accepting two protons.

SPECIFIC TYPES OF
POLYPROTIC
• monoprotic acid: acid containing one ionizable
hydrogen atom per molecule.
• stepwise ionization: process in which an acid is
ionized by losing protons sequentially.
• triprotic acid: acid that contains three ionizable
hydrogen atoms per molecule.

ACTIVITY AND
ACTIVITY
COEFFICIENT

ACTIVITY OF THE ION
• The effective concentration of ions in solution is lower than the
actual solution. Therefore, activity related to the concentration
is:
• For an electrolyte, the activity of the individual ions is generally
unequal.

c = concentration of molar units (mol/L)
• At a very low concentration, the limiting form of this equation is given
by:

MEAN ACTIVITY OF IONS
The activity of electrolytes is also expressed
as the mean activity coefficient:

LIMITING LAW
To measure the activity of an ion C in a solution, the concentration
and activity coefficient must be known.

Application/Importance in Pharmaceutical Industry
•Gives us a simple empirical expression for the properties of this
solution as compared with a perfect solution of the same
composition.
•Allow chemists to quantify the effects that solutes have on
solution properties
•Acid/base character affects drug potency and selectivity, and
has a great impact on both pharmacokinetic and
biopharmaceutical properties.

ACID-BASE
TITRATION AND
TITRATION
CURVE

TITRATION CURVE
• Determining the pH of the solution after each addition of the
standard base
• Obtained adding the same volume of base to the solvent alone
• Subtracted from titration curve for the acid to give the true
titration for the acid
SOLVENT CORRECTION CURVE

Physiologic pH is vital for the normal
functioning of tissues and varies in different
parts of the body. The varying pH of the body
has been exploited to design pH-sensitive
smart oral, transdermal and vaginal drug
delivery systems (DDS). The DDS
demonstrated promising results in hard-to-
treat diseases such as cancer and
Helicobacter pylori infection. In some cases, a
change in pH of tissues or body fluids has
also been employed as a useful diagnostic
biomarker. This paper aims to
comprehensively review the development and
applications of pH-sensitive DDS as well as
recent advances in the field.
This study describes the application of the
pH and its applications in targeted drug
delivery

Recent pioneering work investigated
bicarbonate buffering in the field of drug
supersaturation and precipitation using
poorly soluble drug bases.
Physiological Buffer Effects in Drug
Supersaturation - A Mechanistic Study of
Hydroxypropyl Cellulose as Precipitation
Inhibitor

REFERENCES
Sadikalmahdi Abdella, Fatima Abid, Souha H. Youssef, Sangseo Kim, Franklin Afinjuomo, Constance Malinga, Yunmei Song,
Sanjay Garg,
pH and its applications in targeted drug delivery,
Drug Discovery Today,
Volume 28, Issue 1,
2023,
103414,
ISSN 1359-6446,
https://doi.org/10.1016/j.drudis.2022.103414.
(https://www.sciencedirect.com/science/article/pii/S135964462200407X)
Sadikalmahdi Abdella, Fatima Abid, Souha H. Youssef, Sangseo Kim, Franklin Afinjuomo, Constance Malinga, Yunmei Song,
Sanjay Garg,
pH and its applications in targeted drug delivery,
Drug Discovery Today,
Volume 28, Issue 1,
2023,
103414,
ISSN 1359-6446,
https://doi.org/10.1016/j.drudis.2022.103414.
(https://www.sciencedirect.com/science/article/pii/S135964462200407X

PHYSICAL PHARMACY Report - pH and Buffers.pptx

PHYSICAL PHARMACY Report - pH and Buffers.pptx

Recommended

Recommended

More Related Content

Similar to PHYSICAL PHARMACY Report - pH and Buffers.pptx

Similar to PHYSICAL PHARMACY Report - pH and Buffers.pptx (20)

Recently uploaded

Recently uploaded (20)

PHYSICAL PHARMACY Report - pH and Buffers.pptx