In 1884 the Swedish chemist Svante August Arrhenius

(1859-1927) proposed that acids and bases can be

defined in terms of the chemical species they form when
they dissolve in water.
Arrhenius Acid: According to Arrhenius theory, acid is a
substance which has hydrogen atom and can be given in the
form of hydrogen ion in aqueous solution. Such substances are
called as Arrhenius acids. For example, when acetic acid
(CH3COOH)dissolves in water, it will form acetate ion (CH3COO-)
and hydronium ion (H3O+).
 In the same way, HCl acts as Arrhenius acid in water and it converts to Cl-
ion by transferring hydrogen ion towater.

When Arrhenius acids are in pure state (not in solution) they are
covalent compounds, that is, they do not contain H+ ions. The ions are
formed through an interaction between water and the acid when they
are mixed. Ionization is the process in which individual positive and
negative ions are produced from a molecular compound that is
dissolved in solution.
 STRENGTH OF ARRHENIUS
ACIDS

On the basis of ionization of acid , they can be classified into two types:
Strong acid: Those acids, which are completely ionized and give
maximum number of proton (H+) in a solution are known as strong acid.
The value of acid dissociation constant or strong acids (Ka) is very high.
Hence, the strength of acid is directly proportional to the acid
dissociation constant (Ka).
Example: HCl, HNO3, H2SO4etc.

Weak acid: Those acids which are partially ionized in solution, like,
acetic acid, hydrofluoric acid etc. are known as weak acids. The acid
dissociation constant is less for weak acids compared to strong acids.
Example: CH3COOH,H2CO3, H3PO4 etc.
Arrhenius Base: An Arrhenius base is a hydroxide
containing compound that produces hydroxide ions (OH-
ions) in water. The basic species in Arrhenius theory is
thus the hydroxide ion. For this reason Arrhenius bases
are also called hydroxide bases.
-
Example: NaOH(aq)→ Na + OH produces OH- in water
+

Some other examples of Arrhenius bases are KOH, Ca(OH)2

etc.
KOH(aq)→ K++ OH-
NaOH(aq)→ Na++ OH-
STRENGTH OF ARRHENIUS BASES
On the basis of ionization of base , they can be classified into
two types:
Strong base: Those bases, which when dissolved in water
dissociate completely to give OH- ions are known as strong
bases.
The value of base dissociation constant or strong bases (Kb) is
very high. Hence, the strength of base is directly proportional
to the base dissociation constant(Kb).
Example: NaOH, KOH etc.

Weak base: Those bases which are partially ionized in solution,

are known as weak bases. The base dissociation constant is
less for weak bases compared to strongbases.
Example: NH4OH,Ca(OH)2, Al(OH)3etc.
LIMITATIONS OF ARRHENIUS CONCEPT

I. This concept could not explain acidic and basic

character of certain substances such as NH3,Na2CO3,
CaO(Basic) and CO2, SO2,SO3(Acidic) which do not
contain H+or OH-ions.
II. It could not explain the reaction between an acid
and base in absence of water.
THE BRøNSTED –LOWRY ACIDS AND BASES

In 1923, J.N. Brønsted and T.M. Lowry independently

developed the theory of proton donors and proton
acceptors in acid-base reactions, coincidentally in the
same region and during the same year. The main effect of
the Brønsted-Lowry definition is to identify the proton
(H+) transfer occurring in the acid-base reaction. This is
best illustrated in the following equation:
HA + Z↔ A-+HZ+
Acid Base

Donates hydrogen ions Accepts hydrogen ions.

HCl + HOH → H3O+ + Cl-

+ -
HOH + NH3  NH4 + OH
 Acid: An acid is defined as a substance which has a tendency to give
a proton (H+) i.e. an acid is a proton donor.
Base: A base is defined as a substance which has a tendency to
accept a proton (H+) i.e. a base is a proton acceptor.
Example: (i) HCl + H2O → H3O++ Cl-
H2O→ NH4++ OH
-
(ii) NH3 +
(iii) HCl + NH3 → NH4++Cl-

IMPORTANT RESULTS:
HCl is an acid because it donates a proton to water in (i) and to
NH3in (ii) .
NH3 is a base because it accepts a proton from water in (ii) and HCl
in (iii).
Water act both as an acid as well as a base and hence is called
amphoteric.
To determine whether a substance is an acid or a base, count the
hydrogens on each substance before and after the reaction. If the
number of hydrogens has decreased that substance is the acid
(donates hydrogen ions). If the number of hydrogens has increased
that substance is the base (accepts hydrogen ions). These definitions
are normally applied to the reactants on the left. If the reaction is
viewed in reverse a new acid and base can be identified. The
substances on the right side of the equation are called conjugate acid
and conjugate base compared to those on the left. Also note that the
original acid turns in the conjugate base after the reaction is over.
CONJUGATE ACID-BASE PAIRS
The conjugate acid-base pairs of a compound differs by H+ ion.
Conjugate A cid Conjugate Base + H+

CONJUGATE PAIR I

CONJUGATE PAIR II
 ADVANTAGES OF BRONSTED -
LOWRY CONCEPT
I. It is not limited to molecules but includes even the ionic
species to act as acids or bases.
II. It does not require aqueous medium to explain acidic or
basic nature.
III. It can explain the basic nature of ions or molecules having
no OH-ion. E.g. NH3, Na2CO3etc.

LIMITATIONS OF BRONSTED -LOWRY CONCEPT

I. It could not explain the acidic and basic nature of
compounds having no tendency to lose or gain H+ions. E.g.
CO2,NH3,SO2,SO3etc.
II. It could not explain the basic nature of compounds having
OH-ions. E.g. NaOH, Ca(OH)2, KOHetc.
An important way in which scientific knowledge
advances is by modifying and extending a model
to include unstudied species.
In 1923, G.N. Lewis proposed a broader concept
of acids and bases. This concept eliminated the
necessity of the presence of hydrogen in an acid
and this included many more substances as acids
and bases.
According to this concept, an acid is an electron
pair acceptor while a base is an electron pair
donor.
Lewis Acid: A Lewis acid is an electron pair acceptor. The
accepted electron pair is shared between the acid and the
base in the covalent bond. Thus, Lewis definition of acidity
includes many species in addition to H+.

For example, various metal cations, such as Mg2+and metal

compounds such as AlCl3 are Lewis acids because they
have unfilled valence orbitals and can accept electron
pairs from Lewis bases.
 TYPES OF LEWIS ACIDS
i. Molecules having a central atom with incomplete octet. E.g.
BF3,AlCl3,FeCl3.
ii. Simple cations. E.g. Ag+, Cu+, Fe3+.
iii. Molecules having central atoms with empty d- orbitals. E.g.
SiF4, PCl5.
 STRENGTH OF LEWIS ACIDS
Lewis acid strength is very important for explaining the
interactions of different metal ions with specific interaction
partners within toxified cells. The Lewis acid strength of metal
ions is said to be proportional to the generalized
electronegativity of metals in their oxide form.
The Lewis acid strength expressed as the electronegativity of
metals in their highest oxides is significantly higher for Cr(20.8),
Mo(16.9), W(18.2), Mn(11.2), Re(22.5), Ge(18.0) and Sn(15.3)
than for other metals.
Lewis Base: The substance that donates the
electron pair. The donated electron pair is shared
between the acid and the base in the covalent
bond. In a more general sense, most oxygen and
nitrogen containing organic compounds can act as
Lewis bases because they have pairs of electrons.

• TYPES OF LEWISBASES
• Neutral molecules like NH3,R-NH2,etc.
• All negative ions like F-,Cl-,Br-, I-, OH-,etc.
 STRENGTH OF LEWIS BASES
Lewis base
strength
correlates well
with other
measures of
basicity such as
the pKa. They are
given for a variety
of anions in the
adjacent table.
LIMITATIONS OF LEWIS CONCEPT
I. The necessary requirement in Lewis concept is
the formation of a coordinate bond between
the acid and base.
II. The catalytic activity of an acid is due to H+
(aq.) ion. Since the presence of hydrogen is not
an essential requirement for a Lewis acid,
many Lewis acids will not have this property.
 Acid Dissociation Constant
• The magnitude of the equilibrium constant for an
ionization reaction can be used to determine the
relative strengths of acids and bases.
• For an aqueous solution of a weak acid, the
dissociation constant is called the acid ionization
or dissociation constant (Ka).
• Similarly, the equilibrium constant for the
reaction of a weak base with water is the base
ionization or dissociation constant (Kb).
• Ka is commonly expressed in units of mol/L.
 The Acid-Dissociation Constant (Ka)
Strong acids dissociate completely into ions in water:
HA(g or l) + H2O(l) H3O+(aq) + A-(aq)
In a dilute solution of a strong acid, almost no HA molecules
exist: [H3O+] = [HA]init or [HA]eq = 0
[H O+][A-]
Qc = 3 at equilibrium, Qc = Kc >> 1
[HA][H2O]
Nitric acid is an example: HNO3 (l) + H2O(l) H3O+(aq) + NO3-(aq)
Weak acids dissociate very slightly into ions in water:
HA(aq) + H2O(aq) H3O+(aq) + A-(aq)
In a dilute solution of a weak acid, the great majority of HA
molecules are undissociated: [H3O+] << [HA]init or [HA]eq = [HA]init
[H O+][A-]
Qc = 3
at equilibrium, Qc = Kc << 1
[HA][H2O]
The Meaning of Ka, the Acid Dissociation Constant
For the ionization of an acid, HA:
HA(aq) + H2O(l) H3O+(aq) + A-(aq)
+] [A-] Since the concentration of water is
[H O
Kc = 3
high, and does not change significantly
[HA] [H2O]
during the reaction, it’s value is absorbed
Therefore: into the constant.
[H O +] [A-] The stronger the acid, the higher the [H O+]
Kc = 3 3
[HA] at equilibrium, and the larger the Ka:
Stronger acid higher [H3O+] larger Ka
For a weak acid with a relative high Ka (~10-2 ), a 1 M solution
has ~10% of the HA molecules dissociated.
For a weak acid with a moderate Ka (~10-5 ), a 1 M solution
has ~ 0.3% of the HA molecules dissociated.
For a weak acid with a relatively low Ka (~10-10 ), a 1 M solution
has ~ 0.001% of the HA molecules dissociated.
pH, Buffers and Isotonic
Solutions
 pH
• Definition
pH is defined as negative logarithm of
hydrogen ion concentration.

pH = - log [H3O+] OR pH = log 1/[H3O+]

pH = -log10 [H+]

Where [H+] is the concentration of H+ ion in

solution
27
 pH
• Sorensen’s pH Scale
Aqueous solns – acidic, basic, neutral contains H+ and OH- ions.
The concentration of H+ is 1 x 10-7 and for OH- is 10-7
Therefore the product is 1 x 10-14 which is a constant.
The H+ ion concentration varies from 1- 14 which is conveniently
measured by using Sorensen’s pH scale to express acidity and
alkalinity of the solution and they are measured by using H+ ion
concentration.
pH = 1-7 indicated acidic solution
pH = 7 indicates neutral solution
pH = >7 indicates basic solution
At pH 7 [H +] = [OH-]
pH of 1N HCl = 0 & pH of 1N NaOH = 14
28
29
 Applications of pH
• Enhancing Solubility
– Sodium Salicylate precipitates in acidic pH as Salicylic
acid. Acidic drugs are more soluble in basic pH & vice
versa
• Inceased Stability
– Epinephrine eye drops pH 2.2 – 4.5
– Calcium gluconate inj pH 6.0 – 8.2
– Chloramphenicol ear drops pH 4.0 – 8.0
• Improving Purity
– Insulin precipitates from aqueous solutions pH 5.0 – 6.0
– Amphoteric compounds are least soluble at their isoelecric
point
30
 Applications of pH
• Optimizing Biological Activity
– Optimum pH values are required for enzyme acition. Eg Pepsin pH 1.5

• Comforting the Body

– Blood pH 7.4
– Saliva pH 6.4
– Gastric juices pH 1.0 – 3.0
– Instestinal juices pH 5.0 – 7.0

• Storage of Products
Type III glass containers leach alkali into the formulation
resulting in increased pH. In such cases either a buffer is
employed or Type II or Type I (for parenteral preparations) glass
container have to be employed.
31
 pH- Determination
• pH Indicators.
• pH can also be found out using universal indicators
• Colorimetric method : The color of buffers of known
pH can be matched with the colors of unknown
soution
• pH can be determined using pH meter
• Conductivity meter can be used to determine the pH
by measuring the conductivity of the soln

32
 pH- Determination

• ELECTROMETRIC METHOD
• More accurate

• COLORIMETRIC METHOD
• Involves comparison of solutions of known pH

33
 pH Indicators
• The pH indicator is defined as a solution when added
to a test solution produces a color change, which
helps in determining the pH of the test solution.
Example: Phenolphthalein, Litmus Paper etc.
• Indicators may be weak acid or a weak base
• As the pH varies, the color of the solution changes
due to changes in the degree of ionization.
• Eg Methyl red pH 4.0 RED & 6.0 YELLOW COLOR

34
 Principle of Color change of Indicators
Unionized benzenoid form,

Ionized Quinonoid form,

PINK COLOR
COLORLESS

Phenolphthalein

• The color of the indicator depends on the ionized form and

unionized form of the indicator.
• The con of the unionized form = ionized form when pH = pKa of
the indicator
• Maximum sensitivity of the indicator is seen at this point (pKa
value).
• And the range of the pH lies 1.5 units in either side of the pka
value. 35
Figure 7.3:
The pH
scale and
pH values
of some
common
substances
The pH Values of
Some Familiar
Aqueous
Solutions

[H3O+]
KW
[OH-] =
[H3O+]

[OH-]
[H3O+]> [H3O+]<
[OH-] [OH-]

acidic neutral
solution solution
basic [H3O+] =
solution [OH-]
 The Relationship Between Ka and pKa

Acid Name (Formula) Ka at 25oC pKa

Hydrogen sulfate ion (HSO4-) 1.02 x 10-2 1.991

Nitrous acid (HNO2) 7.1 x 10-4 3.15

Acetic acid (CH3COOH) 1.8 x 10-5 4.74

Hypobromous acid (HBrO) 2.3 x 10-9 8.64

Phenol (C6H5OH) 1.0 x 10-10 10.00

 Acid and Base Character and the pH Scale
In acidic solutions, the protons that are released into solution will not
remain alone due to their large positive charge density and small size.
They are attracted to the negatively charged electrons on the oxygen
atoms in water, and form hydronium ions.
H+(aq) + H2O(l) = H3O+(l) [H+] = [H3O+]
To handle the very large variations in the concentrations of the hydrogen
ion in aqueous solutions, a scale called the pH scale is used which is:
pH = - log[H3O+]
What is the pH of a solution that is 10-12 M in hydronium ion ?
pH = -log[H3O+] = (-1)log 10-12 = (-1)(-12) = 12
What is the pH of a solution that is 7.3 x 10-9 M in H3O+ ?
pH = -log(7.3 x 10-9) = -1(log 7.3 + log 10-9) = -1[(0.863)+(-9)] = 8.14
pH of a neutral solution = 7.00
pH of an acidic solution < 7.00
pH of a basic solution > 7.00
Classifying the Relative Strengths of Acids and Bases–I

Strong acids. There are two types of strong acids:

1. The hydrohalic acids HCl, HBr, and HI
2. Oxoacids in which the number of O atoms exceeds the number of
ionizable H atoms by two or more, such as HNO3, H2SO4, HClO4

Weak acids. There are many more weak acids than strong ones. Four
types, with examples, are:
1. The hydrohalic acid HF
2. Those acids in which H is bounded to O or to halogen, such as
HCN and H2S
3. Oxoacids in which the number of O atoms equals or exceeds by one
the number of ionizable H atoms, such as HClO, HNO2, and H3PO4
4. Organic acids (general formula RCOOH), such as CH3COOH and
C6H5COOH
Classifying the Relative Strengths of Acids and Bases–II

Strong bases. Soluble compounds containing O2- or OH- ions are strong
bases. The cations are usually those of the most active metals:
1) M2O or MOH, where M= Group 1A(1) metals (Li, Na, K, Rb, Cs)
2) MO or M(OH)2, where M = Group 2A(2) metals (Ca, Sr, Ba)
[MgO and Mg(OH)2 are only slightly soluble, but the soluble
portion dissociates completely.]

Weak bases. Many compounds with an electron-rich nitrogen are weak

bases (none are Arrhenius bases). The common structural feature
is an N atom that has a lone electron pair in its Lewis structure.
1) Ammonia (:NH3)
:

:
:
2) Amines (general formula RNH2, R2NH, R3N), such as
CH3CH2NH2, (CH3)2NH, (C3H7)3N, and C5H5N
:

:
 Buffers & Buffering Agents
• BUFFER
Buffer solutions are solutions of compounds or mixtures of
compounds which resist changes in their pH upon addition
of small quantities of an acid or alkali.
Most buffer solutions usually consist of a weak acid
and one of its salts or a weak base and one of its salts.

• BUFFER ACTION
The ability of certain solutions to resist change in their pH
upon addition of an acid or a base is known as the Buffer
action

43
 Mechanism of Buffer action
• Acetic acid (weak acid) and Sodium Acetate (salt of same acid)
Acetic acid = slightly dissociated acid
Sodium acetate = completely dissociated salt
Therefore such a mixture consists of
‘CH3COOH’ molecules and ‘CH3COO-’ & ‘Na+’ ions
If a strong acid is added to the above mixture, the H+ ions supplied
by the acid are immediately taken up by CH3COO- ions to form
the very slightly dissociated CH3COOH.
H+ + CH3COO- = CH3COOH
If a strong base added, the OH- ions supplied by the base are
neutralized by acetic acid present in the mixture and again there is
very little change in pH of the solution
OH- + CH3COOH = CH3COO- + H2O

44
 Mechanism of Buffer action
A mixture of a weak base and its salt also behaves in a similar
manner. E.g. equimolar soln of NH4OH & its largely dissociated
salt NH4Cl.
The mixture contains NH4OH (slightly dissociated) molecules and
NH4+ & Cl- ions.
If a strong acid is added to this mixture, the H+ ions supplied by the
acid are neutralized by the base NH4OH.
H+ + NH4OH = H2O + NH4+
If a strong base is added, the OH- ions are neutralized by NH4+ ions
forming slightly dissociated NH4OH
OH+ + NH4+ = NH4OH
In both the cases there is very little change in the pH
45
 Buffer Equation
Henderson – Hasselbalch equation

• Buffer Equation helps in calculating

– The pH of a buffer solution and
– The change in the pH upon addition of an acid or base.

• Buffer Equation is an expression developed by

considering the effect of a salt on the ionization of a
weak acid or a weak base when the salt and the acid
or base have an ion in common.

46
 Buffer Equation for a
Weak Acid and its Salt / Common Ion Effect
• Let us take an example of the effect of addition of sodium acetate on the
ionization of acetic acid. Both sodium acetate and acetic acid have an
ion common between them, i.e., CH3COO-
The dissociation constant for the acid is given by :
CH3COOH = CH3COO- + H3O+
Ka = [CH3COO-][H3O+]
[CH3COOH]
If sodium acetate is added to the acetic acid solution, it ionizes to give
acetate ion.
CH3COONa ----- CH3COO- + Na+
This causes a momentary increase in the concentration of CH3COO- in the
solution. To re-establish the dissociation constant for the solution, the
hydrogen ion term in the numerator is instantaneously decreased. This
results in the increase of the concentration of CH3COOH in the
denominator
47
• Thus the reaction,
H3O+ + CH3COO- = CH3COOH + H2O
is favoured and the Ka remains unaltered.
In other words, the ionization of acetic acid is repressed upon the
addition of the common acetate ion to the solution and this is
known as the common ion effect
The pH of the buffer soln can be obtained by rearranging the above
equation for the dissociation constant :
[H3O+] = Ka [CH3COOH]
[CH3COO-]

Since acetic acid ionizes only slightly, the concentration of acetic acid
may be considered to represent the total concentration of the acid in
the solution. Hence, the term [CH3COOH] = [acid]. Similarly, the
acetate ion is contributed almost entirely by the salt, Sodium
Acetate, hence, the term [CH3COO-] = [salt]
Therefore, [H3O+] = Ka [acid]
[salt]
48
Expressing in log form,
log [H3O+] = log Ka + log [acid] - log [salt]

Reversing the sign

–log [H3O+] = -log Ka – log [acid] + log [salt]

pH = pKa + log [salt]

[acid]
This is known as the buffer equation or the Henderson – Hasselbalch equation for a
weak acid and its salt.

The buffer equation is useful expression used in the preparation of buffered

pharmaceutical solutions. It is satisfactory for calculations within the pH range of
4 to 10.

49
DERIVATION FOR BUFFERS
FROM WEAK BASES
 Buffer Capacity
• The Buffer capacity of a solution is a measure of its magnitude
of resistance to change in pH on addition of an acid or a base.
It is also referred to as buffer index, buffer efficiency, buffer
coefficient or buffer value.
The buffer capacity β has been defined as the ratio of the
increment of a strong base (or acid) to the small change in pH
brought about by this addition.
β = ΔB
Δ pH
Where ΔB = small increment in gm per lt of a strong base (or
acid) added to the buffer to bring about a pH change of ΔpH

52
According to the eqn, a soln has a buffer capacity of 1 when 1 lt of it
requires 1 gm ≡ of a strong base (or acid) to change the pH by 1 unit.

Hence buffer capacity can also be defined as the amt of a strong acid or
strong base (expressed in gm ≡ per lt) required to change the pH of 1
lt of a buffer system by one unit.
The smaller the pH change in a soln after addition of a specified
amt of acid or base, the greater is the buffer capacity of the solution.
More exact eqn
β = 2.303 C Ka [H3O+]
(Ka + [H3O+])2
Where C = total buffer con, i.e., the sum of the molar con of the acid
and the salt

53
A buffer solution containing a weak acid and its salts has a maximum
buffer capacity (βmax) when the pH is equal to the pKa value for
the weak acid or in equivalent terms
when [H3O+] equals Ka.

Substituting [H3O+] for Ka in the above eqn, we get

βmax = 2.303C [H3O+]2
(2 [H3O+])2

βmax = 2.303 C = 0.567 C

4
For most buffer systems, a total buffer con of between 0.5 and 0.05
mol per lt gives an adequate buffer capacity over a pH range of
about 2 units.
54
Factors affecting pH of Buffer solutions

• Temperature Effects
• Dilution Effects
• Salt Effects

55
 Factors affecting pH of Buffer solutions -
Temperature Effects
The activity coefficient and the pKa value of a buffer
are dependent on the temperature. Hence, buffer pH
changes with temperature.
Buffer consisting of a base and its salt show greater
changes with temp.

An increase in temp lowers the pH of a buffer soln

containing boric acid and sod borate and raises the pH
of a buffer soln containing acetic acid and sod
acetate.
56
 Factors affecting pH of Buffer solutions -
Dilution Effects
Dilution of an aq buffer solutionn with water in moderate
quantities shows only a small effect on the pH of the buffer
soln.
Dilution of an acidic buffer shows an increase in pH while
dilution of a basic buffer shows a decrease.

Quantification of the dilution effect can be done by the use of

dilution value which has been defined as “the change in pH
brought about by the dilution of a buffer solution with an equal
volume of water ”.

The dilution values for most pharmaceutical buffer systems are

usually less than 0.1 pH units. 57
Factors affecting pH of Buffer solutions – Salt
effects
• When a salt is added to a dil buffer soln, the acitivity
coefficients of the ions are lowered.
• Hence, salt added to acidic buffer lowers its pH while
that added to a basic buffer increases its pH.
• However, the change in pH is not greater than 0.1 pH
units provided the final con of the neutral salt added
is not greater than that of the buffer system itself

58
 Biological Buffers
• pH of blood = 7.4 by

• 1°(Primary) buffer components in plasma

• 2°(Secondary) buffer components in erythrocytes

• Plasma = 1) carbonic acid – carbonate

2) acid/alkali sod salts of phosphoric acid

• Erythrocytes = 1) oxyhaemoglobin – haemoglobin

2) acid/alkali (K) salts of phosphoric acid

• Buffer capacity = 0.025 – 0.039 gm≡≡ per lt per pH unit.

• Physiological pH range of blood = 7.0 to 7.8. below and above
which life is in danger. (acidosis & alkalosis).
59
 Measurement of Tonocity

• Hemolytic Method

• Colligative Properties

60
 Isotonic
• Isotonic cellular environments occur when the
concentration outside of the cell and the
concentration in the cytoplasm (inside) of the cell is
the same.

• While water will move in and out, there is no NET

movement of molecules.
 Hypertonic
• Hypertonic environments are created when the
solution outside of the cell has more dissolved solute
than inside of the cell.

• This causes water to move OUT of the cell.

 Hypotonic
• A hypotonic environment for a cell is created when the
solution outside of the cell has LESS dissolved solute
than the cytoplasm of the cell.

• This causes water to move INTO the cell.

Normal Cells in Isotonic Solution Cells in Hypertonic Solution Cells in Hypotonic Solution
 Hemolytic Method
• The solution has essentially the same salt
concentration and hence the same osmotic pressure as
the red blood cell contents and is said to be isotonic
with blood.

• RBCs are suspended in the solution whose tonocity is

to be determined. If the soln cause shrinkage of the
cells, they are said to be hypertonic and if they cause
haemolysis, they are said to be hypotonic.

• Quantitative measurements are also possible using

this method based on the fact that hypotonic
65 solns
liberates oxyhaemoglobin in direct proportion to the
66
 Colligative methods
• Colligative properties of solutions properties
that depend upon the concentration of solute
molecules or ions, but not upon the identity of the
solute.
• Colligative properties include
• freezing point depression,
• boiling point elevation,
• vapor pressure lowering, and
• osmotic pressure.

67
In Vivo biologic buffer systems
• Blood
① Primary buffers : Plasma ;
NaHCO3-- H2CO3, NaHPO4--NaH2PO4, protein
② Secondary buffers : Erythrocytes ;
hemoglobin-oxyhemoglobin, K2Hpo4--KH2PO4

• Lacriminal fluid
- pH: 7.4 (range 7 – 8 or slightly higher)

• Urine
- pH: 6.0 (range 4.5 – 7.8)
- below normal…hydrogen ions are excreted by the kidney.
- above pH 7.4…hydrogen ions are retained by action of the kidney.
68
 Pharmaceutical buffers

• ophthalmic soln.

• colormetric determination of pH

• research studies in which pH must be

held constant

69
 Pharmaceutical buffers
• Clark-Lubs mixtures and pH
(a) HCl & KCl, pH 1.2 - 2.2
(b) HCl & potassium biphthalate, pH 2.2 - 4.0
(C) NaOH & potassium biphthalate, pH 4.2 - 5.8
(d) NaOH & KH2PO4 , pH 5.8 - 8.0
(e) H3BO3, NaOH & KCl, pH 8.0 - 10.0

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Preparation of pharmaceutical buffer solutions
• Steps for development of a new buffer
① Select a weak acid having a pKa approximately equal
to the pH at which the buffer is to be used.

② Calculate the ratio of salt & weak acid required to

obtain the desired pH.

③ Consider the individual conc. Of the buffer salt & acid

needed to obtain a suitable buffer capacity
* Individual conc. : 0.05 ~ 0.5M
* buffer capacity : 0.01 ~ 0.1
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Preparation of pharmaceutical buffer solutions
• Steps for development of a new buffer
④ Availability of chemicals, sterility of the final soln,
stability of the drug & buffer, cost of materials, freedom
from toxicity
ex) borate buffer – toxic effect – not be used for oral or
parenteral products.

⑤ Determine the pH and buffer capacity

using a reliable pH meter

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 Buffer in
pharmaceutical and biologic systems

• Influence of buffer capacity and pH on tissue

irritation
* Tissue irritation will be minimal when…

(a) Buffer solution – β , Volume

(b) Physiologic fluid - β , Volume

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 Buffer in
pharmaceutical and biologic systems

• Stability vs. optium therapeutic response

* Undissociated form of a weakly acidic or basic drug has a

higher therapeutic activity than the dissociated salt form.

* Molecular form is lipid soluble & can penetrate body

membranes readily, where the ionic form, not being lipid
soluble, can penetrate membranes only with greater
difficulty.

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 Buffer in
pharmaceutical and biologic systems
• pH and solubility
* Influence of buffering on the solubility of base
- At a low pH : base is in the ionic form & usually very
soluble in aqueous media

- As the pH is raised : more undissociated base is formed

when the amount of base exceeds the limited water
solubility of this form, free base precipitates from soln.

Base soln. should be buffered at a sufficiently low pH

for stabilization against precipitation.
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