CHM 101 2018-2019

Learning Objectives:

Important applications of equilibra like

•pH
•Solubility
•Solubility of Ionic Solids
Dr Oladoyinbo F. O.
 PH
&
its Applications
COMMON PH VALUES AROUND US

•pH of cheese is between 4.8−6.4.

pH of bananas is between 4.5−5.2.
pH of grapes is between 3.5−4.5.
pH of lime juice is between 2.0−2.4.
IMPORTANCE OF PH

• Our body works within the pH range of 7.0 to 7.8.

• Living organisms can survive only in a narrow range
of pH change.
• When pH of rain-water is less than 5.6, it is called
acid rain.
• When acid rain flows into the rivers, it lowers
the pH of the river water.
• The survival of aquatic life in such rivers becomes
difficult.
PH IN DIGESTIVE SYSTEM -

• The pH in the human digestive tract varies greatly.

• The pH of saliva is usually between 6.5 - 7.5. The

fundic or upper portion of the stomach has
a pH between 4.0 - 6.5,
• lower portion of the stomach secrete hydrochloric
acid (HCI) and pepsin until it reaches a pH between
1.5 - 4.0
PH METER

• A pH Meter is a scientific instrument that measures

the hydrogen-ion concentration (or pH) in a solution,
indicating its acidity or alkalinity.

• The pH meter measures the difference in electrical

potential between a pH electrode and a reference
electrode.
PH IN GROWING CROPS - DEFINITION

• pH is a scale that chemists use to measure

acidity. Values below 7 are considered acidic,
values above 7 are alkaline ( the opposite of
acidic) and 7 is neutral.
• Most plants can tolerate a wide pH range in
solution culture, but they cannot tolerate a
wide range of acidity in the soil.
RANGE OF PH SCALE
• The range of pH scale is from 0 to 14.
The pH value from 0 to 7 indicates the
acidic nature of solution whereas from 7
to 14 indicates the basic nature of
solution. The intermediate value that is
7 indicates neutral nature of solution
such as pure water.
Ammonia or Sodium Hydroxide
show the pH value in the range 7-14,
which reflects their basic nature.
On the contrary, acidic substances like
vinegar, stomach acid, battery acid, coke
etc show pH range from 0-7 that shows
their acidic nature.
 EFFECT OF PH ON PLANTS AND ANIMALS
• High levels of either acidity or alkalinity can be harmful to plants and
animals.
Effect on Plants: Most of the plants do best when soil’s pH is in the neutral
range i.e. 6 to 7. Acidic soil can prevent certain nutrients from being absorbed
by plants that are best absorbed in alkaline soil. In very alkaline soil, certain
important micro-nutrients such as zinc and copper become chemically
unavailable to plants.

Effect on Animals: Effect of pH is most observed for the animals that stay in
water. Acidic water robs fish and other aquatic species of sodium in the blood
and oxygen in the tissues. Additionally, it affects the functioning of fish
gills. Acidic water also poisons fish eggs, as they will not hatch if water pH is
too low.
In addition to the direct effects on fish, acid water also destroys ecosystems by
killing organisms lower on the food chain.
EFFECT OF PH ON TOOTH DECAY
• The saliva in a healthy mouth has a pH of 7.1.

• Certain foods increase the acidity of the mouth and reduce the pH
level. Saliva helps neutralize the acid, but the pH of saliva can
become more acidic after eating acidic foods. It can take between a
few minutes to a few hours for the pH of the mouth to neutralize.

• In that time, the lower pH of the mouth creates an optimal

environment for bad bacteria, which eventually causes tooth decay.
PH OF SOIL IN BACKYARD
• Soil pH is dictated by type of parent material from which soil is
formed, rainfall, organic matter content among others.

• Soil in the backyard would mean it consists of kitchen garden

growing grass, vegetables, trees etc., and it would have been
supplied with some kind of organic amendments, fertilizers etc.,
over a period of time.
• In such a scenario pH of acidic soils would improve and move
towards neutral and pH of alkali soils would also move towards
neutral.
PH OF SALTS
• Salt can be made of either a weak acid and strong base, strong acid
and weak base, strong acid and strong base, or a weak acid and weak
base.
1. Salts that are formed from strong bases and strong
acids will give a pH of 7 in their solution.
2. Salts that are formed from strong bases and weak
acids give a pH greater than 7 in their solution.
3. Salts that are formed from weak bases and strong
acids give a pH of less than 7 in their solution.
pH in Chemistry
• pH is defined as the decimal logarithm of the
reciprocal of the hydrogen ion activity, aH+ in a
solution.

pH= - log +
[H ]
For example,
• For a solution with a hydrogen ion activity
of 5×10−6 (at that level, this is essentially the number
of moles of hydrogen ions per litre of solution)
• There is 1/(5×10−6) = 2×105,
• Thus such a solution has a
•pH of log10(2×10 ) = 5.3 5
pH depends on temperature

For instance at 0 °C the pH of pure

water is about 7.47.

At 25 °C it is 7.00,

and at 100 °C it is 6.14.

 Ion-selective electrodes,
• This definition of pH was adopted because ion-selective
electrodes:
• which are used to measure pH, respond to activity.
• Ideally, electrode potential, E, follows the Nernst equation,
which, for the hydrogen ion can be written as

where E is a measured potential, E0 is the standard electrode potential, R is the gas constant, T is the
temperature in kelvins, F is the Faraday constant.
 pH indicators
• Indicators may be used to measure pH, by making
use of the fact that their color changes with pH.

• Visual comparison of the color of a test solution with

a standard color chart provides a means to measure
pH accurate to the nearest whole number.
• More precise measurements are possible if the color
is measured spectrophotometrically, using
a colorimeter or spectrophotometer.

• Universal indicator consists of a mixture of

indicators such that there is a continuous color
change from about pH 2 to pH 10. Universal indicator
paper is made from absorbent paper that has been
impregnated with universal indicator. Another method
of measuring pH is using an electronic pH meter
 Spectrophotometer

- pH meter -

Universal Indicator
pOH

• pOH is sometimes used as a measure of the concentration

of hydroxide ions, OH−.
• pOH values are derived from pH measurements. The
concentration of hydroxide ions in water is related to the
concentration of hydrogen ions by

where KW is the self-ionization constant of water.

 Taking logarithms

• So, at room temperature, pOH ≈ 14 − pH.

• However this relationship is not strictly valid in other

circumstances, such as in measurements of soil alkalinity.
Neutrality

•Neutrality is defined as the condition

+ −
where [H ] = [OH ] (or the activities
are equal)
• Since self-ionization of water holds,

• the product of these concentration [H+]×[OH−] = Kw, it can be

seen that at neutrality

Therefore, [H+] = [OH−] = √Kw, or

pH = pKw/2. pKw is approximately 14

but depends on ionic strength and temperature, and so the pH of

neutrality does also
Dissociation of Ionic Solids (& Compounds)
• Dissociation in chemistry is a general process in which
molecules (or ionic compounds such as salts, or complexes)
separate or split into smaller particles such as atoms, ions,
or radicals, usually in a reversible manner.
Dissociation in water

• Water is a polar molecule. If we represent water using Lewis

structures we will get the following
 Dissociation of sodium chloride in water
• It is the polar nature of water that allows ionic compounds to dissolve in it.

• In the case of sodium chloride (NaCl) for example, the positive sodium ions (Na+) are
attracted to the negative pole of the water molecule, while the negative chloride
ions (Cl−) are attracted to the positive pole of the water molecule.

• When sodium chloride is dissolved in water, the polar water molecules are able to
work their way in between the individual ions in the lattice.

• The water molecules surround the negative chloride ions and positive sodium ions
and pull them away into the solution.
This process is called dissociation
Sodium chloride dissolves in water
form
For Acids , Bases & Ionic Solids
 Calculating pH for Acids , Bases & Ionic Solids
• [pH] or potential of Hydrogen, is measured on a scale from 0 to 14. 0
being the most ACIDIC, while 14 being the most BASIC
• To find pH from the concentration of H3O+ (or just simply H+) you
need to do the following:
pH= -log[H3O+] or -log[H+]
The [H3O+] or [H+] is just the concentration (in molarity)
If you have the concentration of OH−, however, simply find the pOH by:
pOH=-log[OH−]
• After you get this number, you do the following:
pH= 14-pOH
Related questions
• The importance of water pH is to keep your
body in balance and to regulate metabolic
processes. A diet high in acidity will lead to
weight gain, slower immune response, and
susceptibility to disease, while a diet too
alkaline will lead to inability to metabolize
key nutrients.
OR
Answer
• Correct option is C
• 1 M H2​SO4​ solution
• Given concentration of all the acidic solutions is equal.
However, H2​SO4​ being the strongest acid will dissociate completely
thus giving highest concentration of H+ ions.
pH balance disorders
• A blood pH imbalance can lead to two
conditions: acidosis and alkalosis.
• Acidosis refers to having blood that’s too acidic, or a blood pH
of less than 7.35. Alkalosis refers to having blood that’s too
basic, or a blood pH of higher than 7.45.
• There are different types of acidosis and alkalosis based on the
underlying cause.
• When acidosis or alkalosis is caused by a lung disorder or issue
with exhalation, it’s referred to as “respiratory.” When
acidosis or alkalosis is caused by a problem with the functioning
of the kidneys, it’s referred to as “metabolic.”
Similar Concepts in dissociation
Recap -------Revision
 Table of Common Ions
Common Positive Ions (Cations)
Monovalent Divalent Trivalent
Hydronium (aqueous) O+
H3 Magnesium Mg2+ Aluminium Al3+
Hydrogen (proton) H+ Calcium Ca2+ Antimony III Sb3+
Lithium Li+ Strontium Sr2+ Bismuth III Bi3+
Sodium Na+ Beryllium Be2+
Potassium K+ Manganese II Mn2+
Rubidium Rb+ Barium Ba2+
Cesium Cs+ Zinc Zn2+
Francium Fr+ Cadmium Cd2+
Silver Ag+ Nickel II Ni2+
Ammonium NH4+ Palladium II Pd2+
Thalium Tl+ Platinum II Pt2+
Copper I Cu+ Copper II Cu2+
Mercury II Hg2+
Mercury I Hg22+
Iron II Fe2+ Iron III Fe3+
Cobalt II Co2+ Cobalt III Co3+
Chromium II Cr2+ Chromium III Cr3+
Lead II Pb2+
Tin II Sn2+
You should know the
strong acids & bases
 pH, a Concentration Scale
pH: a way to express acidity -- the concentration of H+ in solution.

Low pH: high [H+] High pH: low [H+]

Acidic solution pH < 7
Neutral pH = 7
pH = log (1/ [H+]) = - log [H+] Basic solution pH > 7
Acid Formula pH at half
equivalence
point
Acetic CH3COOH 4.7
Nitrous HNO2 3.3
Hydrofluoric HF 3.1
Hypochlorous HClO 7.4
Hydrocyanic HCN 9
 pH, a Concentration Scale
• A convenient way to express the acidity and basicity of a solution is the pH
and pOH scales.
• The pH of an aqueous solution is defined as:

Acid Formula pH

Acetic CH3COOH 4.7

Nitrous HNO2 3.3

Hydrofluoric HF 3.1

Hypochlorous HClO 7.4

Hydrocyanic HCN 9
 1. Add solution from the
Titration buret.
2. Reagent (base) reacts with
compound (acid) in solution
in the flask.
3. Indicator shows when exact
stoichiometric reaction has
occurred.
4. Net ionic equation
H+ + OH- --> H2O
5. At equivalence point
moles H+ = moles OH-
Titrant
Equivalence Point
Primary Standard
End Point
Secondary Standard
Titration
http://www.chem1.com/acad/webtext/abcon/abcon-2.html
 Autoionization of Water
• Because water is amphiprotic, one water molecule can react with another
to form an OH– ion and an H3O+ ion in an autoionization process:
2H2O(l)⇋H3O+ (aq) + OH– (aq)
• Equilibrium constant K for this reaction can be written as
[H3O+] [OH–]
Kc =
[H2O]2

• When pure liquid water is in equilibrium with hydronium and hydroxide

ions at 25ºC, the concentrations of hydronium ion and hydroxide ion are
equal:

[H3O+]=[OH–] = 1.0 x 10–7 M [H3O+][OH–] = 1.0 x 10–14 M = Kw

pH = pOH = 7 pH + pOH = pKw = 14
Kc [H2O]2 = Kw = [H3O+][OH–] = 1.0 x 10–14
New Topic
Solubility and
Complexation
Equilibria
CHAPTER OBJECTIVES
• To be able to calculate the solubility of an ionic compound
from its Ksp

• To understand the factors that determine the solubility of ionic

compounds

• To be able to describe complex-ion formation quantitatively

• To understand why the solubility of many compounds depends

on pH
 What is Solubility
• Solubility is the property of
a solid, liquid or gaseous chemical
substance called solute to dissolve in a
solid, liquid or gaseous solvent.

• The solubility of a substance fundamentally

depends on the physical and chemical
properties of the solute and solvent as well
as on temperature, pressure and presence
of other chemicals (including changes to
the pH) of the solution
• Solubility may be stated in various units of concentration such as
molarity, molality, mole fraction, mole ratio, mass (solute) per volume
(solvent) and other units.
• A number of other descriptive terms are also used to qualify the extent of solubility
for a given application. For example, U.S. Pharmacopoeia gives the following
terms:
Determining the Solubility of
Ionic Compounds
 Definition of TERMS: The Solubility Product, Ksp
• When a slightly soluble ionic compound is added to water, some of it dissolves to
form a solution, establishing an equilibrium between the pure solid and a solution
of its ions.

• The equilibrium constant for the dissolution of a sparingly soluble salt is the
solubility product of the salt, Ksp.

• The concentration of a pure solid is a constant and does not appear in the
equilibrium constant expression.

• Solubility products are determined experimentally by either directly measuring the

concentration of one of the component ions or by measuring the solubility of the
compound in a given amount of water.

• Ksp is defined in terms of molar concentrations of the component ions.

 Definition of TERMS: The Ion Product
• The ion product (Q) of a salt is the product of the concentrations of
the ions in solution raised to the same powers as in the solubility
product expression.
• The ion product describes concentrations that are not necessarily
equilibrium concentrations, whereas Ksp describes equilibrium
concentrations.
• The process of calculating the value of the ion product and comparing
it with the magnitude of the solubility product is a way to determine if
a solution is unsaturated, saturated, or supersaturated
and whether a precipitate will form when solutions of two soluble
salts are mixed.
 Definition of TERMS: The Ion Product
• Three possible conditions for an aqueous solution of an
ionic solid
1. Q < Ksp: the solution is unsaturated, and more of the ionic solid will
dissolve
2. Q = Ksp: the solution is saturated and at equilibrium
3. Q > Ksp: the solution is supersaturated, and ionic solid will precipitate
 Definition of TERMS: The Common Ion Effect and Solubility

• Solubility product expression

– Equilibrium concentrations of cation and anion
are inversely related

– As the concentration of the anion increases, the

maximum concentration of the cation needed for
precipitation to occur decreases, and vice versa

– Ksp is constant
Solubility of ionic compounds in water

• Some ionic compounds (salts) dissolve in water, which arises

because of the attraction between positive and negative
charges.

• For example, the salt's positive ions (e.g. Ag+) attract the
partially negative oxygens in H2O. Likewise, the salt's negative
ions (e.g. Cl−) attract the partially positive hydrogens in H2O.

• Note: oxygen is partially negative because it is

more electronegative than hydrogen, and vice versa
Solubility product, Ksp.
• However, there is a limit to how much salt can be dissolved in a
given volume of water.

• This amount is given by the solubility product, Ksp.

• This value depends on the type of salt (AgCl vs. NaCl, for
example), temperature, and the common ion effect.
Calculation of Solubility
• One can calculate the amount of AgCl that will dissolve in 1 liter
of water.
• Some algebra is required:
Ksp = [Ag+] × [Cl−]
(definition of solubility product)
• Ksp = 1.8 × 10−10 (from a table of solubility products)
• [Ag+] and [Cl−] are conc of Silver and Chloride ions
respectively
Interpretation
• Ag+] = [Cl−], in the absence of other silver or chloride salts,
• [Ag+]2 = 1.8 × 10−10
• [Ag+] = 1.34 × 10−5
• Meaning of the result: 1 liter of water can dissolve 1.34 × 10−5 moles
of AgCl(s) at room temperature.
• Compared with other types of salts, AgCl is poorly soluble in water. In
contrast, table salt (NaCl) has a higher Ksp and is, therefore, more
soluble.
Factors That Affect Solubility
 Factors That Affect Solubility

• The solubility product of an ionic compound describes the concentrations of

ions in equilibrium with a solid.

• There are four reasons that the solubility of a compound may be other than
expected:
1. Ion-pair formation
2. Incomplete dissociation of molecular solutes
3. Formation of complex ions
4. Changes in pH
(O level concepts…: Temperature, Pressure, Polarity and rate
of dissolution)
Ion-Pair Formation

• An ion pair consists of a cation and anion that are in intimate

contact in solution, rather than separated by solvent.
 Ion-Pair Formation
• Ions in an ion pair are held together by the same
attractive electrostatic forces as for ionic solids.
– Ions in an ion pair migrate as a single unit, whose net
charge is the sum of the charges on the ions.

– The ion pair is a species intermediate between the ionic

solid (in which each ion participates in many cation-anion
interactions that hold the ions in a rigid array) and the
completely dissociated ions in solution (where each is fully
surrounded by water molecules and free to migrate
independently).
Ion-Pair Formation
• Ion pairs
– A second equilibrium must be included to describe the solubility of
salts that form ion pairs.

– An ion pair is represented by the symbols of the individual ions

separated by a dot, to indicate that they are associated in solution
(Ca2+ ·SO42–).

– The formation of an ion pair is a dynamic process, so a particular ion

pair may exist only briefly before dissociating into the free ions, each
of which may later associate briefly with other ions.

– Ion-pair formation has a major effect on the measured solubility of a

salt and is most important for salts that contain M2+ and M3+ ions; it
is unimportant for salts that contain monocations.
Incomplete Dissociation

• A molecular solute may be more soluble than

predicted by the measured concentrations of ions in
solution due to incomplete dissociation.
– Common for weak organic acids
– Weak acids do not dissociate completely into their
constituent ions (H+ and A–) in water
– The molecular (undissociated) form of a weak acid (HA) is
quite soluble in water
– Many carboxylic acids have a limited solubility in water
Incomplete Dissociation
Complex-Ion Formation
 Complex-Ion Formation
• Metal ions in aqueous solution are hydrated—surrounded by a shell of four to six
water molecules.

• A hydrated ion is one kind of complex ion, molecules or ions that contain at least
one lone pair of electrons. , a species formed between a central metal ion and one
or more surrounding ligands (Note the definition)

• A complex ion forms from a metal ion and a ligand because of a Lewis acid-base
interaction.
– The positively charged metal ion acts as a Lewis acid, and the ligand, with one or more lone
pairs of electrons, acts as a Lewis base.
– Small, highly charged metal ions have the greatest tendency to act as Lewis acids and to
form complex ions.
The Formation Constant

• The equilibrium constant for the formation of

the complex ion from the hydrated ion is
called the formation constant (Kf).

• Equilibrium constant expression for Kf has the

same general form as any other equilibrium
constant expression.

• The larger the value of Kf, the more stable the

product.
The Effect of Complex-Ion Formation on Solubility

• The solubility of a sparingly soluble salt increases if a

ligand that forms a stable complex ion is added to the
solution.
• The formation of a complex ion by the addition of a
complexing agent increases the solubility of a compound.
• Complexing agents are molecules or ions that increase
the solubility of metal salts by forming soluble metal
complexes. (Note the definition)
Other examples of complexing agents are: EDTA, Ammonia, phosphates, phosphonates,
polycarboxylates, and zeolites
Solubility and pH
Solubility and pH

• Solubility of many compounds depend strongly on the

pH of the solution

– The anion in many sparingly soluble salts

is the conjugate base of a weak acid that
may become protonated in solution.
– The solubility of simple binary
compounds such as oxides and sulfides
are dependent on pH.
The Effect of Acid-Base Equilibria on the Solubility of Salts
• Examining the effect of pH on the solubility of a
representative salt, M+A–, where A– is the conjugate base of
the weak acid HA
– When the salt dissolves in water, this reaction occurs:
M A(s) ⇋ M+(aq) + A–(aq) Ksp = [M+] [A–]
– The anion can also react with water in a hydrolysis reaction:
A–(aq) + H2O(l)⇋OH–(aq) + HA(aq)
– If a strong acid is added to the solution, the added H+ will
react essentially completely with A– to form HA, which
decreases
[A–] and which in turn decreases the magnitude of the ion
product, Q = [M+] [A–]

– More MA will dissolve until Q = Ksp

Solubility and Partition
Phenomena
Contents
Solubility

• Definitions
• Factors influencing solubility
• The effect of pH on solubility
• The effect of pressure
• Influence of solvents on solubility
Contents
Partition Phenomena

• Partition concepts
• For weak electrolytes as solutes
• Drug absorption
• pH partition hypothesis
• Site of drug partitioning
Definitions
• Solubility is the concentration of a solute when the solvent has
dissolved all the solute that it can at a given temperature

• Martin’s Physical Pharmacy & Pharmaceutical Sciences 6th edition

Patrick J. Sinko
Factors influencing solubility
• Dissolution of a crystal

1. A solute (drug) molecule is

removed from its crystal
2. A cavity for the molecule is
created in the solvent
3. The solute molecule is
inserted into this cavity

* Physicochemical Principles of Pharmacy 4th edition

Alexander T Florence and David Attwood
Factors influencing solubility
• Temperature & Pressure

• Solubility is an equilibrium value that

is dependent on a given temperature
and pressure

• Solubility does not depend on how

fast a substance dissolves in
the solvent
Factors influencing solubility
• Temperature * Table. Heat of solution

Solute ΔHsoln (25℃) kcal/mole

• Heat of solution (ΔHsoln) HCl - 17.96
NaOH - 10.6
• The enthalpy change associated CH3COOH - 0.36
with the dissolution of a
substance in a solvent NaCl + 1.0
KMnO4 + 10.4
Mannitol + 5.26
KI + 4.3
 Factors influencing solubility
• Chemical structure

• Dipole moment

• A measure of polarity
Molecules that have a
high dipole moment are
more soluble in polar
solvents such as water
 Factors influencing solubility
• Chemical structure * Table 6-5 Dielectric Constants of
Some Solvents at 25℃

• Dielectric properties Dieletric

Solvent
constant
Water 78.5
• Related to the ability Glycerin 40.1
to store charge Propylene glycol 32.01
Methanol 31.5

• How a substance Acetone

PEG 400
19.1
12.5
interacts with solvents Cottonseed oil 6.4
Ether 4.3
* Applied Physical Pharmacy
Mansoor M.Amiji, Beverly J.Sandmann
 Factors influencing solubility
• Chemical structure

• Hydrogen bonding

• The attractive interaction of a

hydrogen atom with an
electronegative atom, such as • Amines with small alkyl groups
are very soluble in water. This is
nitrogen, oxygen or fluorine because hydrogen bonding occurs
between the amine and water
• Major factor on solubility in molecules
water
Factors influencing solubility
• Chemical structure
*
• Hydrogen bonding

• The attractive interaction

of a hydrogen atom with
an electronegative atom,
such as nitrogen, oxygen
• The presence of hydroxyl groups
or fluorine or nitro groups can markedly
• Major factor on solubility increase the solubility.
in water
* Physicochemical Principles of Pharmacy 4th edition
Alexander T Florence and David Attwood
Factors influencing solubility
• A high melting point means *
low water solubility

• cis (z) Isomer is more soluble

than trans (e) isomer

* Physicochemical Principles of Pharmacy 4th edition # Kirk-Othmer Encyclopedia of Chemical Technology

Alexander T Florence and David Attwood 18 OCT 2001
 The effect of pH on solubility
• Acidic drugs (HA)

• Total saturation solubility of drug S, the solubility of the

undissociated species HA S0

S = S0 + (concentration of ionised species)

By changing the pH of the solution, you can change the charge state of the solute. If the pH of the solution is such that a
particular molecule carries no net electric charge, the solute often has minimal solubility and precipitates out of the solution.

* Physicochemical Principles of Pharmacy 4th edition

Alexander T Florence and David Attwood
The effect of pH on solubility
• Acidic drugs (HA)

• The dissociation constant Ka

• According to previous page, [HA] = S0, [A-] = S – S0

The effect of pH on solubility
• Acidic drugs (HA)
• Taking logarithms,

• [A-] = S – S0, S0 = [HA]

<Henderson-Hasselbalch Equation>
The effect of pH on solubility
• Basic drugs (RNH2)

• Total saturation solubility of drug S, the solubility of the

undissociated species RNH2 S0

S = S0 + (concentration of ionised species)

The rate at which a drug goes into the solution when it is dissolved in an
acidic or a basic medium is proportional to the solubility of the drug. Many
drugs have different solubilities at different pHs. These pH-dependent
solubility differences lead to pH- -dependent dissolution profiles.
* Physicochemical Principles of Pharmacy 4th edition
Alexander T Florence and David Attwood
The effect of pH on solubility
• Basic drugs (RNH2)

• The dissociation constant Kb

• According to previous page, [RNH2] = S0, [RNH3+] = S – S0

The effect of pH on solubility
• Basic drugs (RNH2)
• Taking logarithms,

• [RNH3+] = S – S0, S0 = [RNH2]

<Henderson-Hasselbalch Equation>
The effect of Pressure
• Henry’s Law

C2= σp

C2= concentration of the dissolve gas (g/l)

p = partial pressure (mm of the undissolvegas)
σ= inverse of the Henry’s law constant, K
• In a dilute solution at constant temperature, the concentration of
dissolved gas is proportional to the partial pressure of the gas above
the solution at equilibrium
Influence of (Co)Solvents on Solubility
• Strong electrolytes

• Strong acids and bases and all salts are soluble in

water
• The polar nature of water attracts the ions

• Weak electrolytes

• Weak acids and bases with high molecular weight are

not soluble in water
• Cosolvents such as alcohol, propylene glycol and
polyethylene glycol are required for solubility
 Influence of Solvents on Solubility
• Cosolvents

• Solubility enhancements caused

by co-solvent addition occur
because of changes in the bulk
properties of the isotropic
solution
Water Solubility of Ionic Compounds
If one ion from the “Soluble
Compound” list is present in
a compound, the compound
is water soluble.
Other Applications of Solubility

• Solubility is of fundamental importance in a large number of

scientific disciplines and practical applications, ranging from

• ore processing and nuclear reprocessing to

• the use of medicines,

• and the transport of pollutants.

• In separation techniques
 Application of Solubility : liquid–liquid
extraction
• The synthesis of benzoic
acid from phenylmagnesium bromide and dry ice.
Benzoic acid is more soluble in an organic solvent
such as dichloromethane or diethyl ether, and
when shaken with this organic solvent in
a separatory funnel, will preferentially dissolve in
the organic layer. The other reaction products,
including the magnesium bromide, will remain in
the aqueous layer, clearly showing that separation
based on solubility is achieved. This process,
known as liquid–liquid extraction, is an important
technique in synthetic chemistry.
 Wishing the best in
CAT and examination