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Acids, Bases & Buffers

Introduction
• Acids and bases are the most important pharmaceutical
substances.
• Many active pharmaceutical ingredients are insoluble in water
and aqueous solutions of such agents cannot be prepared.
• Many acid and bases are use in the preparation od suitable
salt of drugs.
• E.g. Diclofenac sodium, atropine sulphate
• Almost 80% of drugs are in suitable salt form.
• Buffers are equally important in case of pharmaceutical
formulations.
• Body has its own buffer system and it gets altered giving rise
to certain ailments.
Various concepts of Acids and Bases
• Although various concepts have been evolved for acids
and bases, all have certain limitation and wherever these
theories are applicable, they can be applied with equal
confidence.
• Earlier concept of Acid And Base:
• An Acid – any substance which has a sour taste and its
aqueous solution turns blue litmus red.
• A Base - any substance which has a bitter taste and its
aqueous solution turns red litmus blue.
Various concepts of Acids and Bases
• Arrhenius Concept:
• The concept of acid and base was first of all introduced by
Arrhenius.
• According to him,
• Acid – any substance that produce H+ ions in aqueous
solution or any substance capable of providing hydrogen ions
(Protons, H+) in aqueous solution.
• Base - any substance that contain OH group or any substance
capable of providing hydroxyl ions (OH-) in aqueous solution.
HCl ↔ H+ + Cl-
NaOH ↔ Na + + OH-
Various concepts of Acids and Bases
• Arrhenius Concept:
• According to him, the neutralization process can be
represented by a reaction involving the combination of H+
and OH- ions to form water.
H+ + OH- ↔ H2O
• Limitations:
• Although the Arrhenius acid base theory is most simple and
convenient in explaining the reaction in aqueous solution.
– The definitions of acids and bases are only in terms of aqueous
solution and not in terms of substances.
– Theory cannot explain acidic and basic properties of substances in
non-aqueous solvents. E.g. NH4NO3 in liquid NH3 acts as an acid,
though it does not give H+ ions
• Limitations:
– The neutralization of acid and base in absence of solvent could
not be explained.
– few basic substances which do not have OH- ions can not be
explained by the theory. E.g. NH3
– It cannot explain the acidic character of certain slats such as
AlCl3 in aqueous solution.
Various concepts of Acids and Bases
• Bronsted Lowry Concept:
• According to them,
• Acids – any particle that donate proton in a chemical reaction.
• Bases - any particle that accept proton in a chemical reaction.
HCl ↔ H+ + Cl-
Acid: donate Proton
H3O+ ↔ H+ + H2O

OH- + H + ↔H2O
Base: Accept Proton
NH3 + H + ↔ NH4 +
• Acids and bases exist side by side.
• This theory is not limited to water as a solvent.
• An acid and a base connected in this way are said to be
conjugated acid-base pair.
• Bronsted Lowry Concept:
• Bronsted acid ionizes to produce proton and conjugate base
of acid, which can be explained by following half reactions of
ionization.
Acid ↔ H+ + Conjugated base
HCl ↔ H+ + Cl-
H3O+ ↔ H+ + H2O
• On the other hand, bases are usually considered as neutral
molecules, or anions, and few cation accepting proton. The
species formed when base accepts proton is called as
conjugate acid. E.g.
Base + H + ↔ Conjugate acid
OH- + H + ↔H2O
NH3 + H + ↔ NH4 +
• The acid base pairs, the members of which can be formed
from each other mutually by the gain or loss of proton are
called conjugate acid base pair.
HCl + H2O ↔ H3O+ + Cl-
Acid1 + Base2 ↔ Base1+ Acid2
Acid1 + Base2 ↔ Conjugated Acid + Conjugated base
• Water can accept proton, thus acting as base and can also
give proton, thus acting as acid. Due to this property of water,
it is called as amphoteric substance.
Acid Base Conjugate Conjugate
Acid Base
HCl + H2O ↔ H3O+ + Cl-
H2SO4 + OH- ↔ H2O + HSO4-
• According to above description, a strong acid is one which
easily give away protons to base, so conjugate base of such
acids, must be weak.
• If conjugated base form is strong, then it will accept the
proton more easily and weaken the strength of acid.
• In general,
• strong acids have weak conjugate bases
• Strong base have weak conjugate acids.
• These concepts are important in the considerations of buffers
and buffer mechanisms.
• This theory is useful while considering the strength of acid
and measuring the pH and pKa.
• Advantage:
• Very simple and easy to apply to many acids and bases.
• The relative strength of acids and bases in aqueous solvent
can be very useful in developing suitable buffers.
• This theory can be applied while applying the calculation of
pH, pOH, pKa etc., which is important in deciding the
physiological characteristics and physiological behaviour of
acids and bases.
• Advantage:
• Very simple and easy to apply to many acids and bases.
• The relative strength of acids and bases in aqueous solvent
can be very useful in developing suitable buffers.
• This theory can be applied while applying the calculation of
pH, pOH, pKa etc., which is important in deciding the
physiological characteristics and physiological behaviour of
acids and bases.
• Lewis Concept:
• It is know as electron donor acceptor concept.
• Acid: any substance or species (molecule, ion or radical)
which can accept an electron pair to the form a coordinate
bond OR is an electron pair acceptor.
• Base: any substance or species (molecule, ion or radical)
which can donate an electron pair to the form a coordinate
bond OR is an electron pair donor.
• According to theory, the process of neutralization is simply
the formation of a coordinate bond between an acid and a
base.
H+ + :NH3 → H←NH3 (NH4+)
BF3 + :NH3 → BF3←NH3 (BF3NH3)
Lewis Concept:
• It is know as electron donor acceptor concept.
• Acid: H+, NH4+, Na+, K+,Cu+2, Al+3
• Base: NH3, H2O, OH-, Cl-, CN-,S-2
• Bronsted acid, the proton is also lewis acid but all lewis
acids are not bronsted acids, vice versa.
• Limitations:
• Substances that are not normally considered as acids, behave
as Lewis acids. Eg.BF3
• As the strength of an acid or a base varies with the solvent,
also depends upon the type of reaction, there can be no scale
of acid and basic strength.
Relative Strength of Acid and Bases
• Acids and bases can be identified as monoprotic or
polyprotic depending upon the numbers of dissociable
protons the acid contains or the number of protons with
which the base can combine.
• Irrespective of whether a substance is monoprotic or
polyprotic, the strength of an acid or base refers to the
efficiency with which the substance demonstrates the
properties of an acid or base.
• For acid – the ease with which it donates protons
• For base – the ease with which it accepts protons
• These properties of substance will be affected by its
environment.
Relative Strength of Acid and Bases
• With respect to strength, there are two general classes
• Strong – are ones which are almost completely dissociated in
dilute aqueous media
• Weak – are ones which are only partially dissociated in dilute
aqueous media
• The strength of acid or base is most frequently determined
by the dissociation constant “K”.
• Strength of Acid – Ka
• Strength of Base – Kb or Ka of its conjugate acid
Images: Strong Acids, Department of Chemistry, CSU From the Virtual Cell Biology Classroom on ScienceProfOnline.com
From the Virtual Cell Biology Classroom on ScienceProfOnline.com
Relative Strength of Acid and Bases
• Strength of Acid – is usually based on the degree of
dissociation of proton from conjugate base when acid is
dissolved in water.
• Ka is ionisation constant for acid. it is expressed as product of
equilibrium constant and concentration of water.
HA + H2O ↔H3O+ + A-
Keq = [H3O +] [A-] / [HA] [H2O]
Ka = Keq [H2O] = [H3O+] [A-] / [HA]
• pKa = - log Ka
• pKb = - log Kb
HA(aq) 
 H 
A 
Ka 
H A 
 

HA
(aq) (aq)

 logKa   log H   log


  A  

HA
pK a  pH  log
 A  

HA
 pH  pK a  log
base
acid 
pH  pK a when A   HA
-
If pH = pKa, [HA] = [A-]
If pH < pKa, [HA] > [A-]
If pH > pKa, [HA] < [A-]
Measurement of acidity and basicity
• pH: is a method of expressing the hydrogen ion
concentration [H+] or hydronium ion [H3O+] concentration
in solution. It is equal to the negative log of the molar
hydrogen concentration .
pH = -log[H+]

• pOH: is a method of expressing the hydroxyl ion


concentration [OH-] in solution. It is equal to the negative
log of the molar hydroxyl ion concentration .
pOH = -log[OH-]
Measurement of acidity and basicity
• Ionization of water:
• Water ionizes slightly to yield hydronium and hydroxyl ions
H2O + H2O ↔H3O+ + OH-
Keq = [H3O +] [OH-] / [H2O] [H2O]
The dissociation constant for water (Kw) = [H3O +] [OH-] = 1.0 x
10-14
pKw is equal to the negative log of dissociation of water
pKw = - log kw = pH + pOH = 14
Measurement of acidity and basicity

Sr. Acidity or
Substance Formula Ka pKa Kb pKb
No Basicity

1 Formic acid HCOOH 1.77 X 10-4 3.75


CH3COO ↑
2 Acetic Acid 1.76 X 10 -5 4.75 - Increasin
H
g Acidity
Trimethylacet (CH3)3CC
3 4 X 10-6 5.03 -
icacid OOH
4 Ammonia NH3 5.62 X 10-10 9.25 1.77 X 10-5 4.75

Trimethylami Increasin
5 (CH3)3N 1.55 X 10-10 9.81 8.32 X 10-5 4.19
ne g Basicity
6 Diethylamine (CH3)2NH 1.85 X 10-11 10.73 5.25 X 10-4 3.28
Importance of Acids and Bases in Pharmacy
• They play vital role in pharmacy practice.
• Some of the main application of these are as follows:
– Acid base neutralization reactions find use in preparative procedures
for the preparation of suitable salts and for conversion of certain
salts into more suitable forms, preparing effervescent mixtures.
– They are used in analytical procedures i.e. titration
– Use as therapeutic agents in the control of and adjustment of the
pH of GIT, body fluid and urine.
– Used as buffers.
pH Scale
• pH: is a method of expressing the hydrogen ion
concentration [H+] or hydronium ion [H3O+] concentration
in solution. It is equal to the negative log of the molar
hydrogen concentration .
pH = -log10[H+]

• pOH: is a method of expressing the hydroxyl ion


concentration [OH-] in solution. It is equal to the negative
log of the molar hydroxyl ion concentration .
pOH = -log[OH-]
pH + pOH = 14
Relation between [H+], [OH-], and pH
[H+] M
100 A strong acid
10-1
10-2
10-3
10-4
10-5
10-6
10-7
10-8
10-9
10-10
10-11
10-12
10-13
A strong base
10-14

The pH scale goes from 0 to 14—because [H+][OH-] = 10-14


Acidosis And Alkalosis
• Acidosis:
• Altered carbonic acid and bicarbonate levels in blood change
the blood’s pH.
• By decreasing the amount of breathing (Hypoventilation),
insufficient CO2 is released.
• The increased level of carbon dioxide in the blood leads to
increased carbonic acid and hydrogen ion levels and
respiratory acidosis results.
• Fainting can occur from mild acidosis
• Coma can be occur from severe acidosis
Acidosis And Alkalosis
• Alkalosis:
• By hyperventilation (overbreathing), an excessive amount of
CO2 is released. To compensate carbon dioxide level more
hydrogen ions and bicarbonate ions combine to form
carbonic acid, which decomposes to water and carbon
dioxide. The reduction in hydrogen ion concentration leads
to respiratory alkalosis.
Buffers
• Buffers:
• It is a solution that resists changes in pH upon addition
of small amount of acids and bases.
• A buffer solution consists of a mixture of weak acid and
its salt or of weak base and its salt.
• Types of buffer solution:
1. Acidic Buffer Solution:
– The solution having a mixture of weak acid (Acetic acid) and its salt
(Sodium acetate)
2. Basic Buffer Solution:
– The solution having a mixture of weak base (Ammonium
hydroxide) and its salt (Ammonium chloride)
Buffers
• Properties of Buffer solution:
– The pH of buffer solution remains constant
– The pH of solution does not change on dilution
– The pH does not change even after addition of small quantities of
acids or bases
– The pH of solution remaining constant is useful in number of
chemical reactions
– The pH of buffer solution does not change on keeping for long
time
• Buffer action:
• In non buffer solution, when small amount of acid is added,
it has tremendous effect on the hydrogen ion concentration.
• In buffer solution, such a drop or rise in pH is certainly
avoided.
• The two components present in buffer system complement
each other.
• Thus, in case of acidic buffer, on addition of small amount of
acid, the added acid reacts with conjugate base forming the
weak acid, which due to its weak nature cannot dissociate
further.
• Buffer action:
• When small amount of base is added to such buffer, the
added base reacts with weak acid forming water and
conjugate base which because of common ion effect
suppresses the dissociation of weak acid. The net result is no
change in pH is occurs. This is only possible when small
amounts of acid or base is added.
• For Example,
• Acidic buffer is prepared by mixing acetic acid (CH3COOH -
weak electrolyte) and sodium acetate (CH3COONa – Strong
Electrolyte) hence the dissociation of acetic acid get
suppressed due to common ion effect. The result is the
solution is having less H+ ion and more Na+ and CH3COO-
ions.
• When small quantity of an acid is added, H+ ions of it
combine with CH3COO- to form undissociated CH3COOH. pH
does not Change.
H+ + CH3COO- ↔ CH3COOH

• When small quantity of base is added, the OH- ions get


neutralized by acetic acid and pH does not Change.
OH- + CH3COOH ↔ H2O + CH3COO-
• For Example,
• Basic buffer is prepared by NH4OH and NH4Cl addition of
small quantity of base OH- react with NH4+ ions and pH
does not change.
NH4+ + OH- ↔ NH4OH

• When small quantity of acid is added NH4OH neutralize it


and pH does not Change.
H+ + NH4OH ↔ H2O + NH4+
• It is possible to calculate the pH of acidic buffer by
Henderson Hasselbalch equation.
Henderson Hasselbalch equation
• pH of acidic buffer solution and maximum buffer action: the
hydrogen ion concentration obtainable from the dissociation
of a weak acid HA, is given by the equation.
HA ↔ H+ + A-
Ka = [H+ ] [A- ] / [HA]
[H+] = Ka [HA] / [A- ]
Log [H+] = log Ka + log [HA] / [A- ]
- Log [H+] = - log Ka + log [A- ] / [HA]
pH = pKa + log [A- ] / [HA]
pH = pKa + log [conjugated base ] / [acid]
• With the help of this equation it is possible to calculate the
pH of a buffer solution of known concentration.
• Alternatively one can make buffer solution of known pH.
• The maximum buffer action is obtained when the
concentration of the acid and the conjugated base are equal
because under these conditions.
pH = pKa + Log 1 = pKa + 0 = pKa (Constant)
• If the concentration of acid is 10 times the concentration of
the conjugate base
pH = pKa + Log 1/10 = pKa – 1
• If [conjugate base]/[acid] = 10, then
pH = pKa + Log 10 = pKa + 1
• It follows from this that a particular acid can be employed
for making useful buffer solution of pH lying within the range
of pKa-1 to pKa+1.
• The maximum buffer action will be attained in half
neutralized reaction (concentration of conjugate base =
concentration of acid).
• For Example,
• The pKa of acetic acid is 4.75 at 25oC and hence mixture of
acetic acid and sodium acetate can be used to make buffer in
the range of 3.75 – 5.75.
• pH of an alkaline buffer:
• Th epH of an alkaline buffer solution made from a weak base
and its salt with a strong acid can also be calculated in a
similar way.
• The ionization of a weak base BOH is given by
BOH ↔ B+ + OH-
Kb = [B+ ] [OH- ] / [BOH]
[OH- ] = Kb [BOH] / [B+ ]
Log [OH- ] = log Kb + log [BOH] / [B+ ]
- Log [OH- ] = - log Kb + log [B+ ] / [BOH]
pOH = pKb + log [B+ ] / [BOH]
pOH = pKb + log [conjugated acid ] / [base]
pH = 14 – pOH
pH = 14 – (pKb + log [conjugated acid ] / [base])
• Buffer Capacity (β) :
• Often it is necessary to know the effectiveness of a buffer on
a quantitative basis. To do so, we employ the term buffer
capacity (β) first introduced by Van Slyke in 1922.
• “It is defined as the amount of acid or base that must be
added to the buffer to produce a unit change of pH.”
• It is clear that the term refers to how much acid or base the
buffer can consume.
• Other proposed to mean buffer capacity as the quantity of
acid or base can be consumed within a specified amount of
pH change.
• Buffer capacity can be defined in terms of the slope of the
Henderson Hasselbalch equation.
• Equation for Buffer Capacity derived by Van Slyke:
• For an aqueous solution, the buffer capacity is define in
terms of the concentration of acid or base that must be
added to influence pH.
• Β = d[Cb] / d[pH] = d[Ca] / d[pH]
• Where,
• Cb = concentration of added base
• Ca = concentration of added base
• Buffer capacity is always positive.
• Buffer capacity measures how well a solution resists changes in
pH when acid or base is added.
• The greater the buffer capacity, the less the pH changes.

• The amount of
H+ or OH-
• that buffered
solution can
• absorb without a
significant
• change in pH
• The plot of buffer capacity versus pH for
acetate buffer is represented below:

4.5

• Buffer capacity for the acetate buffer system pKa = 4.5.


• A relative maximum occurs at pH = pKa = 4.5
• Buffer capacity is influenced by the concentration of
buffering species.
• Usually, ten fold increase in the concentration of buffering
species results in a ten fold increase in the buffer capacity.
Thus, in following representation, it can be seen that as the
ration of [A-]/[HA] changes, the pH also changes and the
d(pH0 values also changes.
[A-]/[HA] Representativ Representativ
e effective pH e effective
d(pH)
100/100 7.208 -
99/101 7.199 0.009
101/99 7.217 0.009
1000/1000 7.208 -
999/10001 7.1972 0.008
• Thus higher the concentration of buffering species, high is the
buffer capacity.
• This is because buffer capacity increases as d(pH) deceases.
• The criteria for buffers suitable for use in biological research may
be summarized as follows:
– Possess adequate buffer capacity in the required pH range
– Be available in a high degree of purity
– Be very water soluble and impermeable to biological membranes
– Be enzymatically and hydrolytically stable
– Possess a pH which is minimally influenced by their concentration,
temperature and ionic composition or slat effect of the medium
– Not be toxic or biological inhibitors
– Only form complexes with cations that are soluble
– Not absorb light in the visible or UV regions
– Not participate in redox reactions
– Not form complexes with API
– Not alter solubility of the other ingredients
– safe
• Selection of Buffer:
• While selecting a buffer for pharmaceutical purpose or for
analytical purpose, two deciding factors are mainly
considered.
• Physicochemical factor
• Pharmacological factor
• Physicochemical factor:
– The buffer system should not undergo reaction (i.e. acid base
reaction, redox reaction, solubility change, do not form
complexes) with the other chemicals in the preparation.
– The buffer system must possess reasonable chemical stability.
– Buffer acid should be selected so that it is having a pKa near
the middle of the desired pH range of buffer which cause
proper [base]/[acid] ratio.
– Buffer capacity has been found to depend on absolute
concentration of each buffer compound. The higher the actual
concentration selected, the better would be the buffering
capacity of the system for a given [base]/[acid] ratio.
• Pharmacological factor:
– Toxicity of buffers: when selecting buffer system, its toxicity
must be taken into consideration. Some of buffers are having
limited use in pharmaceutical practice due to their toxicity.
– Effect on the pharmacological action of preparations: the
buffer system should neither contribute nor reduce the
pharmacological action of API rom the preparations.
– Contamination by microorganisms: many buffer systems
support microbiological growth because they can serve as
nutrient media for molds and microorganisms particularly
when the pH become close to neutrality. Contamination can
be indicated by clouding of a clear solution. Solutions of such
compounds could be preserved by adding low concentration
of quaternary ammonium antimicrobial agents. E.g. 0.002%
benzalkonium chloride
• Application of buffers:
• It plays a very important role in pharmaceutical preparations
and in analytical procedures.
• Solubility:
• Color:
• Stability of drugs and pharmaceutical agents:
• Chemical instability of compounds:
• Patient comfort:
• Optimum activity of the medicinal preparation:
• In analytical procedures:
Physiological Acid Base balance
• The number of hydrogen ions present in a solution refers to a
measure of the acidity of the solution .
• Body fluids are having balanced quantities of acids
and bases. The maintenance of the normal pH range
within the body fluids becomes essential since the
biochemical reactions that take place in the living
systems are very sensitive to even small changes in
acidity or alkalinity.
Physiological Acid Base balance
• For example, the low pH value in the stomach provides the
environment which is best suited to the functioning of the
enzyme pepsin that helps in digestion of dietary protein.
• Saliva is having a pH range of 5.4 and 7.5 which is necessary
for optimum functioning of ptyalin, an enzyme present in
saliva which digests the carbohydrates. The pH values of
certain body fluids are given as bellows:

Urine 4.5 to 8.0 Blood 7.4 to 7.5

Gastric juice 1.5 to 3.5 Saliva 5.4 to 7.5


Bile 6.0 to 8.5 Semen 7.2 to 7.6
Physiological Acid Base balance
• As the kidneys are able to remove excess acid from the body,
urine can be quite acidic. The range of pH of the blood
compatible with life has been 7.0 to 7.8.
• The metabolic activity of the body cells gives rise to certain
acids and alkalis which are able to alter the blood pH.
• Even though strong acids and bases are continually taken into
and formed by the body, the pH of fluids inside and outside
cells remains fairly constant due to the presence of buffer
systems.
• Most buffers in the human body are having a weak acid and
the salt of that acid.
• The main function of a buffer system is able to convert strong
acids or bases into weak acids or bases.
Physiological Acid Base balance
• The buffer system is able to prevent drastic changes in the pH
values in the blood.
• However, it becomes effective only if there exists some means
by which excess acid or alkali can be excreted out of the body.
• This job is best undertaken by organs like lungs and the
kidneys.
• When respiration gets decreased, the accumulated carbon
dioxide combines with water to form carbonic acid.
• The latter dissociates to release hydrogen ions and gives rise
to acidosis.

CO2 + H2O → H2CO3 → H+ + HCO3-


Physiological Acid Base balance
• Similarly, if there occurs 'over breathing', excessive excretion
of carbon dioxide takes place. This gives rise to alkalosis.
• While the kidneys have the ability to generate ammonia
which neutralizes the acid products of protein metabolism.
The neutralization products then get excreted in the urine
• Besides controlling fluid imbalances, electrolytes also play a
vital role in regulating the body acid-base balance.
• This balance is maintained by controlling the H+
concentration of body fluid especially extracellular fluid In a
healthy adult, the pH of the extracellular fluid happens to be
between 7.35 and 7.45.
Physiological Acid Base balance
• The normal concentration of H+ in body fluids is only 40
Eq/lit.
• Although some hydrogen ions are able to enter the body
in ingested foods, the cellular metabolism of glucose,
fatty acids and amino acids gives rise to a Significant
excess of hydrogen ions.
• As most metabolic reactions take place only within a very
narrow pH range, homeostasis of H+ concentration
Becomes essential for survival and is done through the
major mechanisms.
Buffer System of Body
• In our body, there are many buffer systems which prevent
rapid and drastic changes in the pH of a body fluid by
converting strong acids and bases into weak acids and
bases. Thus, buffers are able to remove the excess H+ ions
from the body fluids but not from the body. The following
are the major buffer systems of the body fluid:
i. Carbonic Add-Bicarbonate buffer system:
ii. Phosphate buffer system:
iii. Protein (Heamoglobin) Buffer System:
Buffer System of Body
• (i) Carbonic Add-Bicarbonate Buffer System: (20:1)
• It is found in plasma and kidneys.
• It is a important regulator of blood pH.
• If there occurs an excess of H+ the bicarbonate (HCO3-) ion
acts as a weak base and accepts H + to form carbonic acid.
• The latter dissociates further to yield carbon dioxide and
water molecules.
H+ + HCO3- →H2CO3 →H2O + CO2
• While if there occurs shortage of the carbonic acid
(another component of buffer system) ionizes to release H+
ions and maintains the pH.
H2CO3 → H+ + HCO3-
Buffer System of Body
• (i) Carbonic Add-Bicarbonate Buffer System:
• In lungs, for example, oxygen reacts with the protonated
deoxy-haemoglobin, releasing protons.
• These protons combine with the bicarbonate, to form
carbonic acid, which then dissociates to yield carbon dioxide
and water.
• Normal metabolism gives rise to more acids than bases. As the
blood is made more acidic, the body requires more
bicarbonate salt than it requires carbonic acid.
Buffer System of Body
• (ii) Phosphate Buffer System: (4:1)
• This buffer system is able to maintain physiological pH at 7.4.
but the phosphate concentration is highest in intracellular
fluids.
• Therefore, the phosphate buffer system is an important
regulator of pH of cytosol.
• This sytem occurs in the cells and kidneys.
• The system consists of monohydrogen phosphate (HPO4-2) /
dihydrogen phosphate (H2PO4-) anions.
• When there exists an excess of H+, the HPO4-2 ion acts as the
weak base by accepting the proton.
HCl + Na2HPO4 → NaCl + NaH2PO4
Buffer System of Body
• (ii) Phosphate Buffer System:
• On the other hand the dihydrogen phosphate ion acts as the
weak acid and neutralize the alkaline condition as,
NaOH + NaH2PO4 → H2O + Na2HPO4
• For Example, in kidneys, NaH2PO4 gets formed when excess
H+ in the kidney tubules combines with Na2HPO4
• Na ion released in this reaction forms NaHCO3 by accepting
HCO3- ion.
• The NaHCO3 then passes into the blood. The kidney are also
able to synthesize new HCO3- and readsorb bicarbonate ions
that have been filtered so this important buffer does not get
lost in the urine.
Buffer System of Body
• (iii) Protein Buffer System:
• This system is the most abundant buffer in body cells and
plasma.
• Proteins are composed of amino acids that are having at least
one COOH group and at least one NH2 group.
• When there occurs an excess of hydrogen ions, the amino
group acts as a base and accepts the proton.
R - NH2 + H+ → R - NH3+
• While the free COOH group can liberate protons to neutralize
an alkaline medium.
R - COOH → R - COO- + H+
• Thus, proteins are able to serve both the functions of acids
and base components of a buffer system due to its amphoteric
nature.
Buffer System of Body
• (iii) Protein Buffer System:
• At physiological pH, Histidine and cysteine are considered to
be most important amino acid buffers.
• Since hemoglobin which is a protein is composed of 37
histidine in its structure, it is an effective physiological buffer.
• When CO2 enters the erythrocytes from the body cells, it
rapidly combines with water to form carbonic acid by the
action of carbonic anhydrase enzyme.
• When there occurs a shortage of H+ ion (alkaline condition) in
erythrocytes, the carbonic acid dissociates into H+ and HCO3-
ions.
• The bicarbonate anion then diffuses out to the erythrocytes.
• The bicarbonate in plasma, along with the plasma carbonic
acid, now acts as an efficient buffer system.
Buffer System of Body
• (iii) Protein Buffer System:
• At the same time, the oxyhemoglobin is able to release its
oxygen to the body cells to become reduced haemoglobin.
• As Hb- carries a negative charge, it accepts a proton and is
able to decrease the excesss of proton (acidic condition) in
erythrocytes.
• In lungs, oxygen combines with the protonated
deoxyhemoglobin, releasing the protons.
• The latter combines with the HCO3- to form carbonic acid,
which then dissociates to carbon dioxide id exhaled out and
water.
• More respiration - ↓ H + concentration – basic pH – alkalosis
• Less repiration - ↑ H + concentration – acidic pH – acidosis
Official Acids

1. Boric acid
2. Hydrochloric acid
3. Dilute Hydrochloric acid
4. Sulphuric acid
5. Dilute Sulphuric acid
6. Phosphoric acid
Boric Acid
• Synonym: Biracic acid, orthoboric acid
• Formula: HH3BO3
• It is having NLT 99.5 % H3BO3
• Preparation:
• It is prepared from native borax and from borates by reacting
them with HCl / H2SO4.
• 1) in the laboratory, it is obtained by adding a mixture of
Conc. H2SO4 and water (1:5) to a boiling solution of Borax
(60gm in 160 ml of water).
Na2B4O7 + H2SO4 + 5H2O → Na2SO4 + 4H3BO3
• The solution is filtered and kept a side for crystallisation. The
crystals of boric acid are separated and then washed until
they become free from sulphate ions. Finally, they are dried at
room temperature.
Boric Acid
• Assay:
An accurately wieghed quantity of boric acid (2g) is dissolved in
a mixture of 50 ml of water + 100ml glycerin

Add drops of phenolphthalein

Titrated with 1 N NaOH


Each ml of 1N NaOH = 0.06183 g of H3BO3
Boric Acid
• Uses:
• It is a local anti infective & used as a dusting powder, local
antiseptic cream, ointments, lotion, etc applied to skin or
mucus or eye
• Aq. Solu. Have been used as mouth washes, eye lotion, and as
douches for irrigating the bladder, vagina and hot
formentation for whitlows, boils.
• It is bacteriostatic, fungistatic properties.
Hydrochloric Acid
• Synonym: Muriatic acid, Spirit of Salt, Acidum
Hydrochloricum
• Formula: HCl
• Spirit of salts: it was first of all prepared by distilling sea salt
with sulphuric acid.
• It is having NLT 35 % w/w and 38% w/w HCl
• Preparation:
• 1) During the manufacture of caustic soda by the elctrolysis of
sodium chloride solution, large quantities of hydrogen and
chlorine gase are obtained as by-product. These gases are
combined to yield hydrogen chloride.
Hydrochloric Acid
• Preparation:
• 2) It is manufactured by the action of sulphuric acid on
sodium chloride .
• Calculated quantities of conc. Sulphuric acid and sodium
chloride are heated in the cast iron pans of a salt cake
furnace.
• The HCL Gas is formed which is passed in a tower , is sprayed
with water.
• The duilute HCl is collected at the bottom.
• It is again circulated to the tower to absorb more HCL so that
it gets concentrated.
Nacl + H2SO4 →NaHSO4 + HCl
NaHSO4 + Nacl →Na2SO4 + HCl
• Assay:
An accurately quantity of hydrochloric acid (4g) is dissolved in 40
ml of water to a stooped flask

Add drops of methyl red

Titrated with 1 N NaOH


Each ml of 1N NaOH = 0.03646 g of Hcl
• Uses:
• Used as a pharmaceutical aid
• As a acidifing agent
• Used as a solvent
• Catalyst in basic pharmaceuticals
• An acidifier

• Dilute Hydrochloric acid: From GIT Agent


Phosphoric Acid
• Synonyms: Orthophosphoric acid
• Formula: H3PO4
• It is having NLT 88 % & NMT 90% w/w of H3PO4
• Preparation:
• On a large scale, orthophosphoric acid is prepared by
• 1) the Wet process
• 2) the pyrolytic or thermal process.
Phosphoric Acid
• 1) The Wet Process:
• In this process, ground phosphate rock or bone ash
[Ca3(PO4)2] is digested with sulphuric acid and filtered to
remove calcium phosphate and other insoluble material.
• The filtrate is having dilute phosphaoic acid which is
concentrated by simple evaporation to about 50% H3PO4.
• The acid so obtained is crude and unless purified it cannot be
used for medicinal and allied purpose.
Phosphoric Acid
• 2) The Pyrolytic or Thermal Process:
• In this process, phosphate rock is mixed with coke and silica
and then heated at a high temperature in an electric furnace.
• The elemental phosphorus is burned to produce P2O5 and it
is dissolved in water to yield phosphoric acid.

Ca3(PO4)2 + SiO2 + 5C →3CaSiO3 + 5CO + 2P


4P + 5O2 →2P2O5
2P2O5 + 3 H2O → 2H3PO4
• The above liquid is transferred to a dish and concentrated.
• Assay:
An accurately quantity of phosporic acid (1.5g) is first mixed
with a solution of NaCl (10g in 30ml of water).

Add drops of Phenolphthalein

Titrated with 1 N NaOH


Each ml of 1N NaOH = 0.04900 g of H3PO4
• Uses:
• Used as a pharmaceutical aid in the preparation of dilute
phosphoric acid.
• Treatment of lead poisoning
• Used in dental cements
• Industrially it is used in beverages as an acidulant
• Aids proteolytic enzyme in the preparation of peptones.
Official Bases
1. Ammonia solution strong
2. Ammonia solution dilute
3. Calcium Hydroxide
4. Sodium hydroxide
5. Potassium hydroxide / solution
6. Sodium carbonate
Ammonia solution Strong
• Synonyms: Liquor Ammoniae Fortis, Ammonium Hydroxide
• Formula: NH3
• M. Wt: 17.03 gm
• It is an aqueous solution of ammonia
• It is having NLT 27 % & NMT 30% w/w of NH3
• Preparation:
• It is manufactured by synthesis from atmospheric nitrogen.
Cynamide process / Haber’s process or may be obtained from
the ammoniacal liquors, from gas works by its distillation with
slaked lime.
N2 + 3H2 → NH3
• Assay:
An accurately quantity of Ammonia (3g) is put in flask which is
already having 50 ml of 1N Sulphuric acid.

Add drops of Methyl Red

Excess acid is Titrated with 1 N NaOH


Each ml of 1N H2SO4 = 0.01703 g of NH3
• Pharmaceutical Uses:
• Due to irritant properties, dilute ammonia is used in
laboratory and pharmaceutical or medicinal uses.
• Used as alkylating agent
• Used as a reflux stimulant in persons who have fainted
• Respiratory stimulant, increased heart rate
• As a rubifacient in the form of liniments
• As a vasoconstrictor.
• Used t reduce flow of nasal secretion in cold
• Is an ingredient of Aromatic Spirit of Ammonia & Storng
ammonium acetate solution
• Uses:
• Used in the preparation of a dilute solution of ammonia, a
storng ammonium acetate.
• Its pharmaceutical applications have been antacid, counter
irritant and stimulant.
• Use for its basic properties, as a laboratory reagent.
Ammonia solution Dilute
• Formula: NH3
• M. Wt: 17.03 gm
• It is an aqueous solution of ammonia
• It is having 9.5 – 10.5 % w/w of NH3
• Preparation:
• It is prepared by diluting the strong ammonia solution with
purified water to be having 10 % w/w of NH3.
• Assay:
• Same as strong ammonia.
Calcium Hydroxide
• Synonym: Slaked lime, hydrated lime, lime water
• Formula: Ca(OH)2
• M. Wt: 74.10 gm
• It contains NLT 90 % of total alkali calculated as Ca(OH)2
• Preparation:
• It is obtained by spraying water on quick lime. This process is
called as slaking.
H2O + CaO → Ca(OH)2↓ + Heat
• The quick lime has to be slaked very cautiously by carefully
spraying or adding water on the lumps of CaO, when they
crumble or disintegrate to a fine white powder occupying
double the volume of the original lump, with considerable
evolution of heat.
Calcium Hydroxide
• Preparation:
• Calcium hydroxide, formed with excess of water, is allowed to
settle.
• The supernatant liquid is decanted and the residue is air
dried.
• The quality of finished product depends upon the purity of
the starting material.
• Assay:
An accurately quantity of Ca(OH)2 (3g) is put in to a 500 ml
botte.

To it 10 ml of neutralized alcohol is added and shaken gently.

Then 490 ml of 10 % w/v of neutralised sucrose solution is


added. The bottel is shaken vigorously for five minutes then at
frequent intervals for four hrs and then filtered.

250 ml of the filtrate is titrated with 1 N HCl, add


phenolphthalein as an indicator
Each ml of 1N HCl = 0.037505 g of Ca(OH)2
• Uses:
• Used as an antacid.
• Use as an astringent in infantile diarroea and vomiting in the
form of water.
• Its solution is used topically as a protective.
• It is also used in the preparation of some skin lotions.

• Storage:
• Must be stored in tightly closed containers as it absorbs
moisture and carbon dioxide.
Sodium Hydroxide
• Synonym: Caustic soda
• Formula: NaOH
• M. Wt: 40.00 gm
• It contains NLT 95 % of total alkali calculated as NaOH
including NMT 3% of Na2CO3.
• Preparation:
• It is obtained by the soda lime process in which sodium
carbonate is heated with milk of lime in large tanks.
Na2CO3 + Ca(OH)2 → CaCO3↓ + 2NaOH
• The product is removed immediately to disallow the reversal
of the reaction. The mother liquor is removed. Then, it is
filtered and evaporated and the mass is processed into flakes,
pellets or sticks.
• Assay:
An accurately quantity of NaOh (1.5g) is put in flask which is
already having 40 ml od Carbon free water

Add drops of Peholphthalein

Cooled and Titrated with 1 N H2SO4


When pink color of the solution is discharged the volume of
titrant is noted then add methyl orange and continue titration
until a persistent pink color is prducesd

Each ml of 1N H2SO4 = 0.040 g of NaOH


• Uses:
• As a strong alkali, it is not therapeutically used.
• Used as a disinfectant for veterinary purpose.
• As a chemical in laboratories and industries.

• Storage:
• Must be stored in tightly closed containers as it absorbs
moisture and carbon dioxide.
Potassium Hydroxide
• Formula: KOH
• M. Wt: 56.10 gm
• It contains NLT 85 % of total alkali calculated as KOH including
NMT 4% of K2CO3.
• Preparation:
• It is obtained by causticizing potassium carbonate with milk of
lime.
K2CO3 + Ca(OH)2 → CaCO3↓ + 2KOH
• The product is removed immediately to disallow the reversal
of the reaction. The mother liquor is removed. Then, it is
filtered and evaporated and the mass is processed into flakes,
pellets or sticks.
• Assay:
An accurately quantity of KOH (2g) is dissolved in 25 ml of water

To it 5 ml of a barium chloride solution is added so as to


precipitate the soluble carbonate as barium carbonate.

Hydroxide left in solution is then Titrated with 1 N HCl using


phenolphthalein as an indicator
When pink color of the solution is discharged the volume of
titrant is noted then add bromo phenol blue and continue
titration until a persistent pink color is produced.
Each ml of 1N HCl = 0.06911 g of K2CO3
Each ml of 1N HCl = 0.05611 pf total alkali KOH
• Uses:
• As a pharmaceutical aid.
• Used in veterinary purpose.
• As a chemical in laboratories and industries i.e. potassium
hydroxide solution, cresol solution, etc.

• Storage:
• Must be stored in well closed containers.
• Great care has to be taken in handling hyroxide, because it is
highly destructive to tissue.

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