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Pharmaceutical inorganic chemistry:- PDF

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Best And Easy Notes For First Semester Pharmacy Students

FIRST YEAR B.PHARM SEMESTER-1

PHARMACEUTICAL INORGANIC CHEMISTRY

Prepared by

A.M.Sekar., M.Pharm,
Assistant Professor,
Department of Pharmaceutical Chemistry,
Surya School of Pharmacy,

Surya Group of Institutions,
Vikravandi-605652

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SYLLABUS

BP104T. PHARMACEUTICAL INORGANIC CHEMISTRY

UNIT I 10 Hours

Impurities in pharmaceutical substances: History of Pharmacopoeia, Sources
and types of impurities, principle involved in the limit test for Chloride, Sulphate,
Iron, Arsenic, Lead and Heavy metals, modified limit test for Chloride and
Sulphate

General methods of preparation, assay for the compounds superscripted with
asterisk (*), properties and medicinal uses of inorganic compounds belonging to
the following classes

UNIT II 10 Hours

Acids, Bases and Buffers: Buffer equations and buffer capacity in general,
buffers in pharmaceutical systems, preparation, stability, buffered isotonic
solutions, measurements of tonicity, calculations and methods of adjusting
isotonicity.

Major extra and intracellular electrolytes: Functions of major physiological
ions, Electrolytes used in the replacement therapy: Sodium chloride*, Potassium
chloride, Calcium gluconate* and Oral Rehydration Salt (ORS), Physiological
acid base balance.

Dental products: Dentifrices, role of fluoride in the treatment of dental caries,
Desensitizing agents, Calcium carbonate, Sodium fluoride, and Zinc ecugenol
cement.

UNIT I 10 Hours

Gastrointestinal agents
Acidifiers: Ammonium chloride* and Dil. HCl

Antacid: Ideal properties of antacids, combinations of antacids, Sodium

Bicarbonate*, Aluminum hydroxide gel, Magnesium hydroxide mixture
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Cathartics: Magnesium sulphate, Sodium orthophosphate, Kaolin and Bentonite

Antimicrobials: Mechanism, classification, Potassium permanganate, Boric acid,
Hydrogen peroxide*, Chlorinated lime*, Iodine and its preparations

UNIT IV 08 Hours

e Miscellaneous compounds
Expectorants: Potassium iodide, Ammonium chloride*.
Emetics: Copper sulphate*, Sodium potassium tartarate
Haematinics: Ferrous sulphate*, Ferrous gluconate
Poison and Antidote: Sodium thiosulphate*, Activated charcoal, Sodium nitrite

Astringents: Zinc Sulphate, Potash Alum

UNIT V 07 Hours

e Radiopharmaceuticals: Radio activity, Measurement of radioactivity, Properties
of a, B, y radiations, Half life, radio isotopes and study of radio isotopes – Sodium
iodide [131 , Storage conditions, precautions & pharmaceutical application of
radioactive substances.

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UNIT-1
IMPURITIES IN PHARMACEUTICAL SUBSTANCES

IMPURITY

A compound is said to be impure if it is having foreign matter is called impurity.
Eg:
Substances such as cane-sugar( sucrose ) , dextrose, common salt and many
inorganic salts, are found with over 99% purity while many others are only having traces
of impurities.

TEST FOR PURITY:

Test for purity for substances so as to ensure their reasonable freedom from the
undesirable impurities. The “Test for Purity” have been in fact the tests for the presence
of impurities and fix the limits of tolerance for these impurities.

Eg:
Arsenic and lead have been dangerous even when ingested in traces.

LIMIT TEST:

Limit tests are quantitative or semi-quantitative tests designed to identify and control
small quantities of impurity which are likely to be present in the substance.

Eg:
1. Limit test for chlorides
2. Limit test for sulphates
3. Limit test for iron
4, Limit test for heavy metals
5. Limit test for arsenic
6. Limit test for Lead

IMPORTANCE OF LIMIT TEST:
e To find out the harmful amount of impurities.

e To find out the avoidable or unavoidable amount of impurities.

SOURCES OF IMPURITIES IN PHARMACEUTICAL SUBSTANCES

The type and amount of impurity present in the pharmaceutical substances, depends upon several
factors. Some of such factors arogqgqybesisebaucation.in
9.

. Raw materials employed in manufacture.

. Reagents used in the manufacturing process.

. Method (or) the process used in manufacture.

. Chemical process used in the manufacture.

. Atomospheric contamination during the manufacturing process.
. Intermediate products in the manufacturing process.

. Defects in the manufacturing process.

. Manufacturing hazards.

Storage condition.

10. Decomposition of the product during storage.

11. Accidental substitution or deliberate adulteration with spurious or useless materials.

1. Raw materials employed in manufacture:
Impurities known to be associated with these chemicals may be carried through the
manufacturing process and contaminate the final compound.
Eg 1:

Rock salt contains small amounts of calcium sulphate and magnesium chloride , so that
sodium chloride prepared from this source will almost certainly contain traces of calcium
and magnesium compounds.

Eg 2:

Zinc sulphate may be prepared by the action of sulphuric acid on zinc metal or zinc

oxide (raw materials).

Zn + H280O4 ————» ZnSO, + H2
ZnO + H28SOQ4—————» ZnSO, + H20

Both zinc and zinc oxide are known to have aluminium, copper, manganese, nickel,
arsenic and iron as impurities. If these impurities are present in appreciable amounts in
the raw materials (zinc metal or zinc oxide), these impurities are likely to be carried to
the final product (ZnSO4. 7H20).

2. Reagents used in the manufacturing process:
If reagents used in the manufacturing process are not completely removed by washing,
these may find entry into the final products.
Eg:

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Ammoniated mercury may be prepared by adding a solution of mercuric chloride to
dilute ammonia solution.

HgCh + 2NHsOH ——» NHoHgCl + NHACI + 2H20
(Soluble) (Soluble) Ammoniated (soluble)
mercury
(Precipitated)

The precipitate of ammoniated mercury (final product) contains ammonium hydroxide.
Therefore, this precipitate is washed with cold water to remove ammonium hydroxide. If it is
not removed completely by washing with water, the final product may contain in it
ammonium hydroxide as impurity.

3. Method or the process used in manufacture

Many drugs and chemicals (especially organic), are manufactured from different raw
materials, by using different methods or processes. Some impurities are incorporated into
the materials during the manufacturing process. The purification of the intermediates has
been also essential, otherwise impurities present in the intermediates, will get
incorporated into the final compound.
a)Reagents employed in the process:
Soluble alkali in calctum carbonate arises from sodium carbonate used in the process.
Calcium carbonate is obtained by interaction of a soluble calcium salt and a soluble
carbonate, and the product is therefore liable to contain traces of soluble alkali, which
the washing process has failed to remove.
b) Reagents added to remove other impurities:
Potassium bromide is liable to contain traces of barium, which is added in the course
of the manufacturing process to remove excess sulphate which in turn arises from the
barium used.
c)Solvents:
Water has been cheapest solvent available and has been used wherever possible,
especially in the manufacturing of inorganic chemicals. Tap water is having ca**,
mg**, Na* , Cl, SO. 2″ and CO3* as impurities in very small amounts. So only used
demineralised water in the manufacturing process.

4, Chemical process used in the manufacture:
For synthesis of drugs, many chemical reactions such as nitration, halogenations,
oxidation, reduction, hydrolysis etc, are involved. In these chemical processes,
different chemicals etc are used. For instance, Potassium iodide is manufactured
from iodine which is obtained from kelp, a sea weed cyanides tend to get formed
when nitrogenous organic matter is burnt with alkalies. Limit tests have been prescribed
for cyanides in KI.

5. Atmospheric contamination during the manufacturing process:
There are many pharmaceutical products which when manufactured are contaminated

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with atmospheric carbon WukWeraanxedugation.in
Eg:
Sodium hydroxide absorbs atmospheric carbon dioxide.

2NaOH + CO2 ——» Na2CO3 + H20

Because of this reaction, sodium hydroxide should not be exposed for a long duration
during its manufacture. Because of this reason, I.P has prescribed that sodium hydroxide
should not contain more than 3 % of sodium carbonate.

6. Intermediate products in the manufacturing process:
There are some intermediates which are produced during the manufacturing process.
Sometimes, these intermediates may be carried through to the final product.
Eg:
Potassium iodide is prepared reacting iodine with potassium hydroxide.

6KOH + 312 ———> 5 KI + KIO; + 3H20
The resulting solution is first evaporates to dryness and then heated with charcoal.

KIO3+3C =——* KI+3CO

In this process, if the intermediates product KIO3 is not completely converted into KI,
then it may be carried through to the final product as an impurity. This impurity is not
desirable and hence pharmacopoeia prescribes a test for iodate in potassium iodide.

7. Defects in the manufacturing process:
In many manufacturing processes, there are defects like imperfect mixing,
incompleteness, non-adherence to proper temperature, pressure, and PH or reaction
conditions. Which may yield chemical compounds with impurities in them.
Eg:
Zinc oxide may be prepared by heating metallic zinc to bright redness in a current of air.
The vapours of zinc burn to form zinc oxide which is collected as a fine white powder.

2Zn +O2 ——» 2ZnO

However, if there is lesser heat or air or both, Zinc metal is not completely converted into
Zinc oxide. Thus, the final product, ZnO may still contain metallic Zinc as impurity.
Therefore, I.P has prescribed, a test for zinc metal in zinc oxide.
8. Manufacturing hazards:

Even in a well-run manufacturing house, certain hazards exist which can give rise to
product contamination. Control analysis will be aware of the more likely hazards, but
even so specifications for drugs and formulated products must be designed to exclude
contamination ranging from the accidental inclusion of particulate matter to microbial
contamination, or even labeling errors.

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The pharmaceutical requirement of sterility test for all products intended for
parental administration and ophthalmic preparations, irrespective of whether they are
prepared by end sterilization processes or produced under septic condition , provides an
adequate level of control for such preparations.

Recommended control of microbial contamination in natural pharmaceutical substances

Freedom from salmonellac:
Acacia: Senna : Tragacanth

Freedom from salmonellae and E.coli:
Cochineal; Digitalis; Gelatin; Pancraetin; Starch; Thyroid

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Freedom from pseudomonas:
Aluminium hydroxide gel: Dried aluminium hydroxide gel: Aluminium phosphate gel.

9, Storage conditions:
The chemicals, substances when prepared, have to be stored in different types of
containers, depending upon the nature of the material, batch size and the quantity.
Various types of materials are used for storage purpose. These may be plastic, polythene,
iron vessels, stainless steel, aluminium, copper etc.
Reaction of these substances with the material of the storage vessels occurs and the
products formed, are found as impurities in the stored material. This reaction may occur
directly or by the “leaching out effect” on the storage vessel. There are many chemical
substances which undergo changes due to careless storage.
Eg:
1. Ferrous sulphate slowly gets changed into insoluble ferric oxide by air and moisture.
2. Surgical solution of the chlorinated soda rapidly deteriorates upon exposure to light
and heat and hence has to be stored in well-closed amber coloured bottle in a cool place.
3. Solution of potassium hydroxide should be stored in well-stoppered bottles of green
glass to avoid a solvent action on lead glass.

All chemicals are stored in tightly-closed containers made of metal or dark glass and
avoid extremes of temperatures, as inorganic chemicals are not much influenced by
ordinary temperature changes. Sunlight affects a large number of chemicals for eg.
Bismuth carbonate gets blackened on long exposure on a shelf exposed to sun light.
10. Decomposition of the product during storage:

Some substances decompose on keeping. The decomposition becomes greater in the
presence of light-air (or) oxygen. The result of decomposition brings about contamination
of the final product. While deliquescent substances absorb water from the atmosphere
and get liquefied.

Many organic substances get spoiled due to decomposition on exposure to the
atmosphere.

Eg: . . .
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Amines, phenols, potent drugs

The decomposition products this appears as impurities in the substances. The use of
ionizing radiations for sterilizing pharmaceutical products may also lead to
decomposition with consequent loss of the medicament and possible formation of toxic
breakdown products.

11. Accidental substitution or deliberate adulteration with spurious or useless
materials:
It is possible to prevent accidental substitution by stocking all more toxic
substances together separately, or in a locked cupboard. Deliberate adulteration is
carried out at many places in india due to improper enforcement of drugs and
cosmetic acts, therefore purchases have to be carried out vigilantly.

There are many pharmaceutical chemicals which are adulterated with cheaper
substances .

eg:

The expensive KBr may be adulterated with cheaper sodium bromide. In order to
avoid the chances of adulteration of KBr, I.P has prescribed a test for sodium in
them.

LIMIT TEST FOR CHLORIDE

Principle:

The limit test for chloride is based on the reaction between silver nitrate and soluble chloride in
the presence of Dil nitric acid. Silver nitrate reacts with chloride ions and form opalescence of silver
chloride which is imsoluble in dil nitric acid. The opalescence produced depends on the amount of
chloride present in the sample. The test opalescence is compared with the standard opalescence which

contain prescribed amount of chloride. This reaction is due to common ion effect.

Nitric acid is used in the test mainly to dissolve the inorganic compound which 1s usually soluble
in HNO3 and also to reduce the solubility product ie. solubility of AgCl is very minimal in HNO3
compared to water. If the test is carried out in neutral medium other acid radicals like carbonate,

bicarbonate may also give precipitate with silver ion.

If the test turbidity is less than the standard turbidity, then the sample passes the limit test for
chloride. Or else it fails the limit test for chloride.

The test is carried out in Nessler’s cylinder.

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HNO;
cl + AgNO; =————>_ AgCly + NOs

Silver nitrate silver chloride

Procedure:

Two Nessler cylinders were taken and labelled one as TEST and other as STANDARD.

TEST STANDARD

1 | Transferred 1 ml of the given sample into | Transferred 1 ml of 0.5845%w/v sodium

the Nessler cylinder and labelled it as test. | chloride solution into the Nessler cylinder and

labelled it as standard.
10 ml of dil HNO3 added.
10 ml of dil HNO3 was added.
5 The volume was made up to 50 ml with
distilled water. The volume was made up to 50 ml with
3 distilled water.
1 ml of AgNO; solution added.
1 ml of AgNO; solution added.
Stirred with glass rod and allowed to
4 | stand for 5 min. Stirred with glass rod and allowed to stand for

5 min.

Both the Nessler’s cylinders were placed against a black background and viewed transversely and

the opalescence produced was compared.
Observation:

The turbidity or opalescence produced in sample was LESS than standard opalescence.
Report:

The given samples PASS the limit test for chloride

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LIMIT TEST FOR SULPHATE
Principle:

The limit test for sulphate is based on reaction between soluble sulphates and barium chloride in
the presence of dil Hydrochloric acid. During reaction, barium sulphate from which, turbidity is produced.
The extend of turbidity 1s high (or) low depends upon the sulphate impurity present in the test substance.
The test turbidity 1s compared with the standard turbidity containing known amount of sulphate turbidity.

This reaction is due to common ion effect.

Barium sulphate reagent contains barium chloride, sulphate free alcohol and a small quantity of
potassium sulphate. The inclusion of potassium sulphate increases the sensitivity of test and acts as a
seeding agent for the precipitation of barium sulphate. Alcohol prevents the super saturation and more

uniform opalescence develops.

If the test turbidity is less than the standard turbidity, then the sample passes the limit test for
sulphate. Or else it fails the limit test for sulphate.

Reaction:
SO? +Backh —p» BaSOQg yy +2ch
Barium chloride Barium sulphate
Procedure:

Two Nessler cylinders were taken and labelled one as TEST and other as STANDARD.

TEST STANDARD

Transferred 1 ml of given sample into | Transferred 1 ml of 0.1089 %w/v of potassium sulphate

Nessler cylinder and labelled as test. solution into Nessler cylinder and labelled as standard.

2 ml Dil Hel was added and diluted to 45 | 2 ml Dil Hcl was added and diluted to 45 ml with distilled

ml with distilled water. water.

5 ml of Barium sulphate reagent was | 5 ml of Barium sulphate reagent was added.

added.

Stirred well and kept aside for 5 mins.
Stirred well and kept aside for 5 mins.

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Both the Nessler’s cylinders were placed against a black background and viewed transversely and

the opalescence produced was compared.
Precautions:
All the apparatus were rinsed with distilled water before use.
All the reagents except standard sulphate solution were sulphate free.
Observation:
The turbidity or opalescence produced in sample was LESS than standard opalescence.
Report:

The given sample PASSE the limit test for sulphate.

LIMIT TEST FOR IRON

Principle:

The Limit test for iron is base on the reaction between ferrous ion and thioglycollic acid in the
presence of citric acid and ammonia producing a pale pink to deep reddish purple colour complex known
as ferrous thioglycolate. The colour is formed due to the formation of ferrous compound with

thioglycollic acid.

Thioglycollic acid acts as a reducing agent and reduces Ferric ion to ferrous ion and the
compound ferrous thioglycolate is produced. Ferrous thioglycolate is colour less in acid and neutral
conditions. The colour develops only in alkalme medium. Hence ammonia is used in this limit test to
maintain the alkaline conditions. Citric acid forms a soluble complex with iron and prevents its
precipitation by ammonia as ferrous hydroxide. Ferrous thioglycolate is stable in absence of air but fades
when exposed in air due to the oxidation of ferrous to ferric compound. Therefore the colour should be

compared immediately after the time allowed for full development of colour 1s over.

S-CH2COOH
2Fe* + 2CH2SHCOOH > 2Fe* + + 2H
S-CH2,COOH

Ferric ion Thioglycollic acid Ferrous ion

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Procedure:

Citric aad
+ 2CH2SHCOOH

=>

Ammonia

CH2SH

A
Cco-O / ne

(Ferrous thioglycolate complex)

0-OC

Two Nessler cylinders were taken and labelled one as TEST and other as STANDARD.

TEST

STANDARD

Dissolved a specified quantity of sample

in 20 ml of water.

2 ml of 20% w/v solution of iron free citric

acid and 0.1 ml of thioglycollic acid were
added.

Iron free ammonia solution was added to

make alkaline.

The volume was made upto 50 ml with

distilled water.

Stirred with glass rod and allowed to

stand for 5 min.

Diluted 2 ml of standard iron solution to 20 ml

of water.

2 ml of 20%w/v solution of iron free citric acid

and 0.1 ml of thioglycollic acid were added.

Iron free ammonia solution was added to make

alkaline.

The volume was made upto 50 ml with distilled

water.

Stirred with glass rod and allowed to stand for

5 min.

The intensity of the colour produced in test and standard solution were compared by placing both the

Nessler cylinders against a black background and viewed transversely.

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Observation:

The intensity of colour produced in sample was LESS than standard.

Report:

The given samples PASS the limit test for iron.

LIMT TEST FOR HEAVY METALS

Principle:

The limit test is for detecting and limiting the impurity of heavy metals likely to
be present in many drugs. The heavy metals are precipitated as their sulphides by the
addition of H2S or Na2S. The sample is dissolved in acid or alkali for making a solution.
If acid is used, the pH is adjusted to a value of 3-4 by adding either dilute acetic acid or
dilute ammonia solution. The limit test 1s done in two 50 ml Nessler cylinders. The test
solution is prepared in one cylinder and standard solution is prepared in the other cylinder

taking the prescribed volume of standard lead solution.

Acetic acid
Pot! + H2S > PbS + H2

(Hydrogen Sulphide)

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Procedure:

Two Nessler cylinders were taken and labelled one as TEST and other as STANDARD.

TEST STANDARD
1 | Dissolved 1 g of sample in 2 ml of dilute | Pipetted out 2 ml of standard lead solution (20
acetic acid and added enough distilled | ppm Pb) into the Nessler cylinder and diluted
water to make up the volume to 25 ml. with distilled water to 25 ml.
2
Either dilute acetic acid or dil ammonia
solution was added to adjust the pH
Either dilute acetic acid or dil ammonia
between 3-4.
solution was added to adjust the pH between 3-
4.
3
10 ml of freshly prepared hydrogen
sulphide solution was added and mixed.
10 ml of freshly prepared hydrogen sulphide
4
Diluted with water to 50 ml and allowed to | solution was added and mixed.
stand for 5min.
Diluted with water to 50 ml and allowed to
stand for 5 min.
Observation:

When viewed downwards over a white surface the intensity of the colour produced in sample was LESS

than standard.
Report:

The given samples PASS the limit test for heavy metals

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LIMIT TEST FOR LEAD

Lead is a most undesirable impurity in medical compounds and comes through use of sulphuric acid, lead

lined apparatus and glass bottles use for storage of chemicals.

Principle

It is based on the violet colour produced in chloroform due to the reaction between lead impurity and
dithizone. Which results in the formation of lead-dithizonate.The intensity of final violet colour produced

in the chloroform medium in compared with standard.

Ce6Hs-N=NCS-NH-NH- CeHs
( Dithizone dissolves in chloroform)
Green colour

It has ability to extract lead as a complex
From substance containing lead as impurity
Trace of other metals, particularly copper and iron, interfere with the test since they also yield dark

precipitate (or) colouration with sodium sulphide.

Addition of ammonia and potassium cyanide before the addition of sodium sulphide, by
formation of complex cyanide, prevents their precipitation as sulphide. So under these conditions lead

alone is precipitated.

ps ys
H
NH-NH-CeHs Alkaline N-N N=N
—
Pb+2S=C~% +> s=c” P< _Cc=s
N=N-CGHs Medium \N=N N-N
| | Hu
CoHs CeHs
Lead Dithizone (Lead- dithizonate complex)
Violet colour
Procedure

Test sample

Standard compound

1.A known quantity of sample solution is

transferred in a separating funnel

1.A standard lead solution is prepared
equivalent to the amount of lead permitted in

the sample under examination

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2.Add 6ml of ammonium citrate 2.Add 6ml of ammonium citrate

3.Add 2 ml of potassium cyanide and 2 ml [3.Add 2 ml of potassium cyanide and 2 ml of

lof hydroxylamine hydrochloride hydroxylamine hydrochloride

4. Add 2 drops of phenol red 4. Add 2 drops of phenol red

5.Make solution alkaline by adding 5.Make solution alkaline by adding ammonia
ammonia solution. solution.

6. Extract with 5 ml of dithizone until it 6. Extract with 5 ml of dithizone until it becomes

becomes green green

7.Combine dithizone extracts are shaken for |7.Combine dithizone extracts are shaken for 30
30 mins with 30 ml of nitric acid and the mins with 30 ml of nitric acid and the

chloroform layer is discarded chloroform layer is discarded

8.To the acid solution add 5 ml of standard |8.To the acid solution add 5 ml of standard

dithizone solution dithizone solution
9. Add 4 ml of ammonium cyanide 9.Add 4 ml of ammonium cyanide
10.Shake for 30 mins 10.Shake for 30 mins
11.Observe the color 11.Observe the color
Observation

The intensity of the color of complex, is depends on the amount of lead in the solution. The color produce
in sample solution should not be greater than standard solution. If color produces in sample solution is

less than the standard solution, the sample will pass the limit test of lead and vice versa.

Reasons

Ammonium citrate, potassium cyanide, hydroxylamine hydrochloride is used to make pH optimum so
interference and influence of other impurities have been eliminated.
Phenol red is used as indicator to develop the color at the end of process
Lead present as an impurities in the substance, gets separated by extracting an alkaline solution with a

dithizone extraction solution.

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LIMIT TEST FOR ARSENIC

Principle:

The test substance is dissolved in hydrochloric acid or an aqueous solution or extract is
acidified. The arsenic present in the sample is converted to either arsenious acid ( trivalent ) or
arsenic ( pentavalent ). Then it is further treated with a reducing agent such as stannous chloride

or sulphurous acid. All the arsenic acid present is reduced to arsenious acid.

The arsenious acid is further reduced to arsine by nascent hydrogen produced by the

action of granulated zinc and hydrochloric acid.

When arsine comes into contact with dry paper saturated with mercuric chloride it
produces a yellow or brown stain. The intensity of the stain is compared by daylight with
standard stain which is similarly and simultaneously prepared by taking a specified quantity of

standard dilute arsenic solution in place of the substance. This test is modified Gutzeit test.

/ 3+ ————————- H3ASO3 ( Arseneous acid)
AS
\ 5+ –n———2————- H3ASOsg (Arsenic acid)
He
H3ASO4_ ——————– H3ASO3 ( Arseneous acid )
Sncb/ Hel
H+
H3ASO3 — ——————– H3AS ( Arsine gas) + H2O0
Znclz / Hcl

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ASH?2

/

2H3AS + Hgcly —————— Hg + Fp

\ ASH:

(Mercuric arsenide- yellow stain)

Apparatus:

The apparatus consists of a wide- mouthed glass bottle or conical flask fitted with a rubber
bung or ground glass stopper. A glass tube of specified dimensions is passed through the rubber
bung. The internal diameter of the tube ( 5mm) is important and should be uniform throughout
the tube is open at the upper end but tapers to a small diameter at the lower end. Near the lower
end a hole is present at the side to allow any condensed moisture to escape.

The tube is first lightly packed with cotton wool saturated with lead acetate and dried. This
is to trap any hydrogen sulphide which may be formed during the reaction if any sulphur
impurity is present in substance. If this not done, the hydrogen sulphide will affect the mercuric
chloride paper.

The mercuric chloride paper is fixed at the upper end of the tube between two rubber
bungs by means of a spring clip. The two rubber bungs contain the tube in two parts and the
mercuric chloride paper is correctly positioned between them.

Mercuric chloride
paper

Lead acetate cotton wool

Fig.1 : Gutzeit apparatus for limit test for Arsenic

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Procedure:

Two clean and dry arsenic apparatus were taken and labeled one as test and another as
standard. Detached the upper part of each apparatus; filled the glass tube of the upper part with
lead acetate dipped cotton swab for a length of 3cm. Mercuric chloride paper was fixed in
position.

S.No TEST STANDARD

1. | Dissolved 0.2g of sample in 50 ml of water. Taken | ml of standard arsenic
solution. ( 10 ppm As) and added 50 ml
of water.

2. | 10ml of stannated hydrochloric acid was

10ml of stannated hydrochloric acid
added.

was added.

lgm of potassium iodide and 10g of

” 1gm of potassium iodide and 10g of
granulated zinc were added.

granulated zinc were added.

Closed the flask immediately and the Closed the flask immediately and the
4. | apparatus was placed in a water bath under apparatus was placed in a water bath

suitable temperature. under suitable temperature.

Heated it for 40 min, mercuric chloride paper

Heated it for 40 min, mercuric chloride
5. | was removed and observed.

paper was removed and observed.

The depth of the colour in the test and standard stain were compared by daylight.
Observation:

The intensity of the stain in the mercuric chloride paper of sample was LESS than the
standard.

Report:

The given sample was PASS the limit test for arsenic.

LIMIT TEST FOR CHLORIDES AND SULPHATES IN POTASSIUM PERMANGANATE.

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Principle:

If the limit test is done in the usual ways , it will be difficult to make an observation since
the sample itself is highly coloured. So potassium Permanganate is eliminated by reduction with
alcohol. This process is called pre-treatment. The sample is dissolved in water, heated on a water
bath, alcohol is added. It is filtered to remove Manganese di oxide. The colourless solution was
used for three tests.

2KMnO, + 3CH3CH2OH ————- 2KOH + 2CH3sCHO + 2H20
Pot. Permanganate ethanol
Cl + AgNO; ne AgCl y + NOs
Silver nitrate silver chloride
SO? + Bach -——–— BaSOs y+ cl

Barium chlorideBarium sulphate

LIMIT TEST FOR CHLORIDES AND SULPHATES IN SODIUM BICARBONATE.
Principle:

Here the Pre-treatment consists of neutralizing the sodium bicarbonate with an
appropriate mineral acid and using the neutralized solution for the particular limit test. In the
case of limit test for chlorides, the sample is dissolved in distilled water and neutralized with

nitric acid.
NaHCO; + HNO; —– NaNO; + CO. + moO

In the case of sulphates the sample is suspended in distilled water and neutralized with

hydrochloric acid.
NaHCO; + HCI —- NaCl + CO. + 20

In both cases, the solutions should be stirred well and the effervescence should be
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UNIT-II

2.2 MAJOR EXTRA AND INTRA CELLULAR
ELECTROLYTES

“+ In the body fluids, there are various inorganic and organic compounds. In a healthy
person, the electrolytes concentration is maintained constant in the body fluids.

“* If a person undergoes surgery or remain ill or remains under undesirable condition for a
long time, the body cannot maintain (or) correct the electrolyte balance, then it is done by
external administration which is termed as “replacement therapy”.

“+ The electrolyte concentrations of body fluids have been different in various body fluid
compartments.

i. Intracellular fluid:

This is the fluid which is present inside the cell. This constitutes 12-15% of body
weight and its volume is 30 litres.

u. Interstitial fluid:

This is the fluid which is present between the cells. This constitutes 12-15% of
body weight and its volume is 10 litres.

ii. Plasma( Vascular fluid):

This is the fluid which is present within the blood vascular system. This
constitutes 4-5% of body weight and its volume is 3-5% litres.

** The body fluids are having various inorganic ions which are either anionic (or) cationic in
character.

Eg. Anionic electrolytes includes HCOz, Cl, SOx? and HPO.” .
A cationic electrolyte includes sodium, potassium, calcium and magnesium.

“+ The concentration of some important electrolytes in the plasma are given in the table.

IONS Plasma (range) MEg/ L
Cations
1. Na* 135 – 145
2. Kt 4.5-5.5
3. Ca’ www.remixeducation.in! ~ 2-6

4. Mg** 1.5-3.0
Anions

1. cr 98-105

2. SO. 0.3-1.5

3. HCOx 25-31

4. HPO4* 1.2-3.0

“* Replacement therapy is to be used when the body itself is unable to correct an electrolyte
imbalance because of a change in the composition of the fluids.

“+ Products which could be used under replacement therapy have been electrolytes acids,
and bases, blood products, carbohydrates, amino acids and proteins. Certain such
conditions are as follows

a) Dehydration:

It refers to the state in which the water volume, but not usually the amount of
solute, has been low in all three compartments.

b) Hypovotemia:
It refers to the state in which the intravascular volume has been low.
c) Edema:

It refers to a condition in which fluid gets accumulated in the interstitial space
because of low osmotic (protein) pressure. Proteins contribute about 1.4m osm/
Litre to the blood plasma. The volume of the third space gradually expands at the
expense of the vascular space and in the most severe cases, death may occur from
too low a circulating blood volume ( hypovolemia) in the presence of total body
edema.

“+ Important functions served by electrolytes in general, are as follows.
a) To control osmosis of water between body compartments.
b) To maintain the acid-base balance needed for normal cellular activities.

c) To generate action potentials and graded potentials and control secretion of some
hormones and neurotransmitted.

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FUNCTIONS OF MAJOR PHYSIOLOGICAL IONS

PHYSIOLOGICAL ROLE OF SODIUM:

Sodium (Na‘) is considered to be the most abundant extra-cellular ion. It constitutes
nearly 90% of extra-cellular cations.

Normal plasma sodium concentration is 136 to 142mEg/ Litre. The normal intake of
sodium chloride per day varies from 5 to 20g and the daily requirement is between 3 to 5

g.
The Na’ level in the blood is controlled by aldosterone and anti diuretic hormone (ADH).

The main component of the extra-cellular fluid is sodium ion which is associated with
chloride and bicarbonate in regulating the acid-base equilibrium.

It helps in the maintenance of osmotic pressure of various body fluids and thereby
protecting the body against excessive fluid loss.

It is of vital importance in preserving normal irritability of muscle and the permeability of
cell.

It plays important role in the transmission of nerve impulses in the nerve fibres.
Conditions under which a high serum sodium level exists(hypernatremia) may be put as
follows

a) Severe dehydration

b) Hyper adrenalism(cushing syndrome)
c) Certain types of brain damage

d) Excessive treatment with sodium salts.

Low serum sodium levels gives rise to dehydration, acidosis and excess leads to edema
and hypertension.

Sign of hyponatremia include muscular weakness, Dizziness, Headache, Hypotension,
Tachycardia and shock.

PHYSIOLOGICAL ROLE OF POTASSIUM:

Normal plasma K* concentration is 3.8 to 5.0 mEq/ L. It is the most abundant cation in
intracellular fluid.

The normal intake of potassium chloride varies from 5 to 7g per day. Human body
usually has about 2.6g per kg body weight of potassium. The daily requirement is about

1.5 to 4.5¢. . . .
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The concentration of muscles, especially that of cardiac muscle.
The transmission of nerve impulses.

Maintaining the electrolyte composition of various body fluids.
In many biochemical activities inside the cells.

Helps to regulate Pâ„¢ by exchange against for hydrogen ions.

Elevated serum potassium levels(Hyperkalemia) are usually seen with patients who are
suffering from renal failure, advanced dehydration (or) shock.

In Addison’s disease there occurs an adrenal insufficiency which elevates, the serum
potassium along with high intracellular potasstum symptoms of Hyperkalemia are mainly
cardiac and C.N.S. depression.

Low serum potassium levels(hypokalemia)develop in various conditions as follows

a) Illness in which post operative treatment which includes IV administration of
solutions not having potassium for a prolong period.

b) They have been associated with malnutrition, gastrointestinal losses, as in diarrhea
and in metabolic alkalosis.

PHYSIOLOGICAL ROLE OF CALCIUM:

The total calcium (ca**) content in body is about 22g per kg body weight and daily
requirement is about 0.8g.

Most of the calctum occurs in bones and remaining is largely found in extra-cellular fluid
compartment.

Daily intake for calcium in adults is about 800 — 1000mg where as the minimum
requirement in an adult is about 400mg per day.

Calcium which plays a vital role in the functioning of nerves and muscles.

Ionized calcium concentration becomes low —+» Tetanic spasms (or) convulsions
may take place

Ionised calcium concentration becomes high —» Cardiac functions are disturbed

The level of calcium ions in the plasma is regulated by parathyroid hormone and
calcitonin.

Calcium is known to get associated with vit.D and phosphorus in the hardening of bones.
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It also gets involved in the coagulation of blood and in impulse propagation and in
muscle contraction.

Calcium is also needed for the release of acetylcholine from the preganglionic nerve
terminals.

PHYSIOLOGICAL ROLE OF MAGNESIUM:

Magnesium is regarded as the second most common intra-cellular electrolyte and the
body’s fourth most abundant.

The daily requirement is about 350mg

Magnesium ions are able to activate enzymes which are involved in carbohydrates and
protein metabolism.

It is also important in neutral transmission, myocardial function and neuromuscular
activity. It is needed for the operation of Na* – kt ATPase pump system.

If patients suffering from malabsorption, diarrhea (or) chronic alcoholism, excessive
losses of dietary magnesium are likely to take place.

Addison’s disease, acute diabetic acidosis, severe dehydration, hypothermia (or) renal
failure, the total body magnesium level increases.

PHYSIOLOGICAL ROLE OF CHLORIDE:
Daily body requirement is about 5 to 10g as sodium chloride.
Chloride ions get excreted mainly through skin during sweating and through urine.

Chloride ion along with sodium ion is able to maintain osmotic balance between different
body fluids.

Chloride ion is able to maintain the charge balance between the body fluids, 1.¢., intra-
cellular and extra-cellular both as they can pass through all membranes.

Chloride ions take part in formation of gastric hydrochloric acid and also in maintenance
of acid-base balance. Under the normal physiological conditions there occurs no
deficiency of chloride ions, but if there occurs more utilization, then deficiency can give
rise to “hypochloremic alkalosis” causing vomiting.

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PHYSIOLOGICAL ROLE OF PHOSPHATE:

The phosphate ions such as H2PO«, HPO.” and PO,* are the main anions of the intra-
cellular fluid compartment.

Among these ions, HPO,*, is found to be the most prevalent form at the physiological P#
7A.

Normal plasma phosphate concentration is 1.7 to 2.6 mEq/L.
Almost 4/5 of the total body phosphate is present in teeth and bones along with calcium.
In the body fluids it occurs as monohydrogen phosphate and dihydrogen phosphate.

One of the important metabolic process in the body is phosphorylation which is able to
convert organic compounds into phosphate esters. This is essential for the proper calcium
metabolism and thus for proper development of teeth and bones.

Phosphate ester bonds in the body happen to be a source of energy.

Phosphate depletion occurs as a result of renal tubular disorders (or) in patients
consuming a large amount of antacids, specifically aluminium hydroxide.

PHYSIOLOGICAL ROLE OF BICARBONATE:
In the extra-cellular fluid compartment, it is second largest anion.

Bicarbonate along with carbonic acid, it acts as one of the important buffer system in the
maintenance of acid-base balance.

A lack of bicarbonate causes the blood P® to go below 7.25 (metabolic acidosis) and an
excess causes metabolic alkalosis.

ELECTROLYTE USED IN REPLACEMENT

THERAPY

Under the normal physiological conditions the body mechanisms are able to adjust the
electrolyte balance and no replacement becomes necessary.

In various conditions such as prolonged fever, severe vomiting or diarrhea, there occurs
heavy loss of water and electrolytes. In order to compensate this, administration of lost
electrolyte in appropriate concentration of tonicity becomes essential.

There are two types of solutions of electrolytes which are used in replacement therapy.

a) A solution for rapid initial replacement:
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This solution is having sodium in the concentration range of 130 — 150mEq/L, 98 —
110 mEq/ L of chlorine, 28 — 55 mEq/ L of bicarbonate, 4 — 12mEq/L of potassium,
3 — 5mEq/L of calcium and 3mEq/L of magnesium.

b) A Solution for subsequent replacement:

The electrolyte composition of such solution is 40 — 120 mEq/L of sodium, 30 — 105
mEq/ L of chlorine, 16 — 53 mEq/ L of bicarbonate, 16 — 35mEq/L of calcium, 3 —
6mEq/L of magnesium and 13mEq/L of phosphorus.

SODIUM CHLORIDE

Molecular Formula: NaCl
Molecular Weight: 58.5 g
Synonyms: Rock salt, Table salt, Common salt

Method of Preparation:

i. In the laboratory it is prepared from common salt (impure) in water by passing
hydrochloric acid gas. The crystals are precipitated out.

ii. Industrially, it is prepared
a) By evaporating purified saline (sea water) deposits and further purification.
b) Itis prepared by purifying rock salt.
NaOH + HC] ———» NaCl + H20
Properties:
e It occurs in the form of a white or colourless powder.
e It is odourless and having saline (salty)taste. It is soluble in water but insoluble in alcohol.
e It can be oxidized chemically and liberates chlorine gas.
2Cl + MnO, + 2H2SO, ——® Mn?* + 280. + 2H20 + Clo

e With silver nitrate solution, it gives a white water insoluble precipitate of silver chloride
which is soluble in ammonia.

NaCl+ AgNO; ——> AgCl 4+ NaNO3
Assay: ( Modified Volhard’s Method-Precipitation Titration):
Principle:

Assay depends upon indirect volumetric precipitation titration. In this case a solution of
the sample of sodium chloride is acidified with nitric acid and is treated with a measured excess

quantity of standard solution of silver nitrate in {he pacgence gn nitrobenzene. Some of the silver
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nitrate is consumed due to reaction with sodium chloride. The remaining unreacted silver nitrated
is then determined by titration with a standard solution of ammonium thiocyanate using ferric
alum (ferric ammonium sulphate) as indicator. Nitrobenzene prevents interaction of silver
chloride with ammonium thiocyanate. The nitric acid to prevent hydrolysis of the indicator i.c.,
hydrolysis of ferric ammonium sulphate.

Naclt AgNO; |= ————> Agel} + NaNO;

The precipitation of silver chloride 1s coagulated by dibuty] phthalate.
AgNO3 + NHsSCN =——* AgSCN_ + NH«NO3
Silver nitrate Ammonium Silver

thiocyanate thiocyanate

NHaSCN + FeNHy4(SOa)2 ————»® Fe(SCN)3 + 2(NHa4)2SO4
Procedure:

Weigh accurately 0.2gm sodium chloride, dissolved 50ml distilled water and then add 0.1M silver nitrate
solution , nitric acid and dibutyl phthalate . Shake the solution add ferric ammonium sulphate indicator
titrate with 0.1M ammonium thiocyanate solution till the colour becomes reddish yellow colour

Uses:

> It is a source of both sodium and chloride ions. The dosage forms are solutions, tablets
and parental solutions.

> 0.9% W/V solution is isotonic and is used as wet dressing and irrigating body cavities or
tissues.

» Hypertonic solutions are used in conditions when there is excessive loss of sodium along
with water.

>» When hypertonic solution is given orally, it induces vomiting and thus can be used in
case of poisoning as a first aid.

> It is constituent of Ringer’s injection, Sodium chloride and potassium chloride I.V
infusion and ORS.

Official Preparations of NaCl:

1. Sodium chloride eye lotion (B.P)

It contains 0.85% to 0.95% W/V of NaCl . It is prepared by dissolving NaCl in purified
water, filtered, transferred to final container, avoiding the entry of micro-organisms and
sterilized by heating in an autoclave.

2. Sodium chloride solution(B.P) . . .
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It contains 0.9% W/V of NaCl, prepared in purified water and clarified by filtration.

3. Sodium chloride injection:

It is a sterile isotonic solution of NaCl in water for injection. It contains not less than
0.85% and not more than 0.95% W/V of NaCl.

Composition:
Sodium chloride———————————– 9g
Water for injection sufficient to produce—–1000ml
4. Sodium chloride injection (Hypertonic)
Composition
Sodium chloride———————————– l6g
Water for injection sufficient to produce—–1000ml
5. Sodium chloride and dextrose injection

6. Mannitol and sodium chloride injection (U.S.P)

POTASSIUM CHLORIDE

Molecular Formula: KCl
Molecular Weight: 74.55 g
Synonyms: Kali Chlordium, Chloropotassuril

Method of Preparation:

I. It is prepared by the action of HCI on Potassium carbonate (or) bicarbonate.
K2CO3 + 2HCl_ ~————» 2KCl1 + H20+ CO2
KHCO3 + HC] ————»_ KCl + H20 + CO2
Properties:
e It occurs as colourless prismatic (or) cubical crystals or as a white granular powder
e It is having saline taste, it is soluble in water, insoluble in alcohol and solvent ether
e It finds use as an electrolyte replenisher

e It also finds use when hypokalemia (or) hypochloremic alkalosis exists as has been the
case after prolonged diarskawwrremixeducation.in
e It is sometimes used as diuretic
e Potassium chloride has been an ingredient of NaCl compound injection, Ringer’s solution.
e It finds use as adjuvant in treatment of “Myasthenia gravis” ( severe muscular weakness)

Official Preparations of KCL:
1. Potassium chloride and glucose I. V infusion (B.P)
2. Potassium chloride and sodium chloride I.V infusion (B.P)

3. Potassium chloride, sodium chloride and glucose I. V infusion (B.P)

CALCIUM GLUCONATE
Molecular Formula: C12H22014 Ca.H20 Molecular Weight: 448.40 g
Structure:

Foo
(CHOP) 4 Ca.H20

CH20H

Method of Preparation:

The gluconic acid is reacting with calcium carbonate to yield the calcium gluconate. The
solution is filtered and calcium gluconate is crystallized from the filtrate.

CH2OH. (CHOH)s. COOH + CaCO; —————» Cpe
(CHOH)4 | Ca. H20 + CO2.
|

CH2OH

Properties:

e It is exists as odourless white crystalline granules or powder.
e It is stable in air, but loses its water of crystallization with decomposition at 100°C.

Assav: (Direct Complexometric titration)

Principle www.remixeducation.in
Calcium gluconate is assayed by Complexometric direct titration method. Some metal
ions like calcium gives a poor end point if titrated directly in these cases replacement or
substitution reaction is used. In this another metal ion is added, eg:-0.05M magnesium sulphate
solution.

Under these conditions mordant black II (Erichrome black, solochrome black) is a
suitable indicator. In the P* range 9 — 11, this indicator is blue and forms red complex with
metals. A buffer mixture with ammonia and ammonium chloride solution is used to maintain the
P# at 10. Four complexes are possible in this titration and the order of decreasing stability in
calcium ededate, magnesium — indicator, calcium — indicator. So it is the order of decreasing
stability.

Hence during the titration, ededate reacts first with free calcium ions then with free
magnesium ions and finally with magnesium indicator complex. Thus, at the end point the colour
changes from wine red to clear blue. It is evident that the volume of 0.05M magnesium sulphate
must be subtracted from the volume of 0.05M disodium ededate used.

Na*OOCH,C CH,COONa*

\ “
Ca2t + / N-CH2-CH2-N \

HOOCH2C CH2COOH

Disodium edetate

|

MePoecrac cHpcoones
/ \ cue. CH2- i
CH2 Ca \
cC— Oo
O O

Ca- EDTA COMPLEX

Procedure:

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Weigh accurately about 0.3g of calcium gluconate and add 50ml of water and add 5ml of

0.05M magnesium sulphate. Add 10ml1 of P® 10 ammonia buffer solution titrate with 0.05M
disodium ededate using mordant black II mixture as indicator the end point is the colour change
from wine red to deep blue, from the volume of EDTA used subtract the volume of magnesium

sulphate added.

Uses:

It finds use as a source of calcium ion for treating hypocalcaemia tetany (or) in calcium
deficiency

Official preparation of calcium gluconate

1.

Calcium gluconate injection
Calcium gluconate tablets.
ORAL REHYDRATION SALT (ORS)

A large number of number of formulation of oral rehydration preparations are available
in the market, which contain anhydrous glucose (or glucose), sodium chloride, potassium
chloride, and either sodium bicarbonate (or) sodium citrate.

These dry powder preparations are to be mixed in specific amount of water and are used
for oral rehydration therapy. These preparations may contain a flavouring agent and a
suitable agent for free flow of the powder.

The following three formulations are usually prepared. When glucose is used, sodium
bicarbonate is packed separately. The quantities given below are for preparing one liter
solution.

Ingredient Formula I Formula II Formula II

Sodium chloride 1.0g 3.5g 3.5g
Potassium chloride 1.5g 1.5g 1.5g
Sodium bicarbonate 1.5g 2.59 | wenn
Sodium citrate fm eee 2.92
Anhydrous glucose 36.4g 20.0g 20.0g
(or) Glucose 40.0g 220g | nese

The formula II and II are recommended by WHO and UNICEF for control in diarrhoeal
diseases.

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PHYSIOLOGICAL ACID-BASE BALANCE AND ITS

IMPORTANCE

Acids are constantly being produced during metabolism. Most metabolic reactions occur
only within a very narrow P® range of 7.38 — 7.42.

The body utilizes several efficient buffer systems
a) Bicarbonate —carbonic acid (HCO3* : H2COs) present in the plasma and kidney.

b) Monohydrogen phosphate —dihydrogen phosphate (HCO.*” ; H2PO.) found in the
cells and kidney.

Carbon dioxide produced in the cells is diffused from the cells into the plasma. A small
portion of CO is dissolved in plasma and another small portion reacts with water to form
carbonic acid which is buffered by plasma protein.

Most of the CO2 enters the erythrocytes where it rapidly combines with haemoglobin or
forms carbonic acid by reacting with carbonic anhydrase.

The P® of the erythrocytes increased due to concentration of carbonic acid is
compensated by haemoglobin.

The bicarbonate anion then diffuses out of the erythrocyte and chloride anion diffuses in.
Carbonic anhydrase

H20 + CO2. —> ECO;

H2CO3 + K* + HbO* + ———» K* + HCO* + HHb + O2

The bicarbonate and plasma carbonic acid acts as an efficient buffer system in plasma ([email protected]
7.4). Oxygen combines with protonated (deoxyhaemoglobin, releasing protons).

“* These combines with bicarbonate yielding carbonic acid which then dissociated to

CO>2 and water. The CO2 is liberated from the lungs.

2.3 DENTAL PRODUCTS

In order to maintain dental hygiene, numerous dental products are available in market.

A large number of inorganic chemicals and their preparations are known which find
application in the practice of dental and oral disorders.

Dental products includes

a) Anticaries agents

b) Cleaning agents (or) BeMMtemixeducation.in
c) Polishing agents
“+ Tooth consists of three layers of calcified tissue namely:

i. Dentine:

It surrounds the pulp cavity and extends throughout the entire portion of
tooth

ii. Cementum:
It is a layer covering the portion of tooth lying buried in the gum
iii. Enamel:
It is white, hard material covering the portion of tooth projecting above the
gum
“* Dentine having 75% of mineral is hard and dense. Enamel having 98% mineral is even
denser.
“+ Vitamin A, C and D are necessary for the proper tooth formation.

Vitamin A deficiency ——» Causes hypo plastic enamel (imperfectly calcified)

Vitamin C deficiency ——» Affects calcification of dentine.

Vitamin D deficiency ——» Vitamin D not only helps the absorption of
calctum from GIT, but also for the proper
deposition of calcium and phosphorous in tooth

Other ions like Mg** , Cl, COs” and citrate are also present in tooth like bones.

“+ A large variety of inorganic compounds are used as dental products in dental care and
treatment. Most dental products are non-prescription and OTC products.

Anti-Caries Agents

Dental caries (or) tooth decay is more (or) less a disease of the teeth caused by acids
produced by the action of micro-organisms on carbohydrates. This disease is
characterized by decalcification of tooth accompanied by foul mouth odour.

Acids produced by bacterial metabolism of fermenting carbohydrates act on teeth,
produce lesions where bacteria’s get localized and dental caries gets produced.

e To prevent dental caries and to maintain clean and healthy teeth, it becomes necessary to
use dentifrices.

Primary function of dentifrice is to clean the accessible surface of the teeth. Use of
ammoniated toothpaste, urea ammonia containing powders, antibiotic containing
mixtures and anti-enzymes. These compounds are having their advantages and limitations.

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Role of Fluorides as Anti-Caries Agents

“+ Role of fluoride in preventing dental caries has been well accepted. Administration of
traces of fluoride having salts or their use in topical use to the teeth has been reported to
give encouraging results.

“+ Fluoride ion is a trace material which occurs in our body. It is generally adequately
obtained from food and water.

“+ In some parts of the world, ground water is totally lacking fluoride. In such places
occurrence of dental caries.

«+ Addition of fluoride to the municipal water supply, known as fluoridation (note: not
fluorination) is able to help in reducing and preventing dental caries.

“+ When a fluoride having salt or solution is taken internally, it is readily absorbed,
transported and deposited in the bone (or) developing teeth and remainder gets excreted
by the kidneys.

“* The deposited fluoride on the surface of teeth does not allow the action of acids or
enzymes in producing lesions. A small quantity (lppm) of fluoride thus becomes
necessary to prevent caries.

«+ If more quantity of fluoride ( more than 2-3ppm) is ingested it is carried to bones and

teeth and gives rise to mottled enamel known as ‘’Dental fluorosis’.

“+ The use of fluoridation of public water supply has been the most common and effective
way of oral administration water supply containing about 0.5 to Ippm is provided which
is sufficient.

«+ Sodium fluoride tablets or solution of sodium fluoride in a dose of 2.2mg per day are
used. For topical application 2% solution is generally used on teeth.

Sodium Fluoride

Molecular Formula: NaF
Molecular Weight: 41.99 g

Synonyms: Chemiflour, Natri fluoridum
Method of Preparation:
It may be prepared by neutralizing hydrofluoric acid with sodium carbonate.

QHF + NaxcCO; ——————> 2NaF + H20 + COQ, *

It involves the double decomposition of calcium fluoride with sodium carbonate wherein
insoluble calcium carbonate can be removed by filtration.

CaF + NasCO; ———» 2NaF + CaCO; 4

Properties:
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It forms colouless, odourless, crystals or as white powder.
It is soluble in water but is insoluble in alcohol.

Assav : (complexometric Titration)

Weighed quantity is dissolved in water. To it a small amount of sodium chloride and

alcohol is added. Now contents are heated to boiling and drop wise excess lead nitrate is added
with stirring. On cooling, coagulated precipitate is filtered, residue washed with dil.alcohol and
the combined filtrate and washings are made to titrate with disodium edate. Xylenol orange as
indicator.

Uses:

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Sodium fluoride due to its fluoride ion is an important agent in dental practice for
retarding (or) preventing dental caries.

DENTIFRICES

Dentifrice is a material which is used for cleaning of teeth and adjacent gums.
One can apply it with finger (or) preferably with a tooth paste. The main drawback is that
it will not be able to clean surface inside cavities and crevices between teeth, even if the
material reaches them during application.
A good cleaning agent must remove stains from teeth and to achieve this suitable
abrasiveness is essential.
The role of phosphate as anticaries and dentifrice is well-known. Calctum phosphate
dibasic and tribasic, sodium metaphosphate are common dentifrice in tooth paste and
tooth powder.

Calcium carbonate and pumice powder also serve as dentifrice agents.

Calcium Carbonate

Molecular Formula: CaCO;
Molecular Weight: 100.1 g

Synonyms: Precipitated chalk, limestone

Method of Preparation:

Calcium carbonate is obtained by mixing the boiling solutions of calcium chloride

and sodium carbonate and allowing the resulting precipitate to settle down.

CaCh + Naxc03 ————> CaC03 V +2NaCl

The precipitate is collected on calico filter , and washed boiling water.

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Properties:

e Itis occur as fine , white , micro-crystalline powder. It is colourless and tasteless.

CaCO3 + H203 Ca (HCO3)2
—_>

Calcium bicarbonate

CaCO3 +2 NH4 . Ca2* +2NH3+ H20 + CO?
—_—_>

Calcium carbonate neutralizes acid with effervescence
CaCO3 + 2HCl ———> CaCl2 + CO2 + H20

Assay (Complexometric method):

Accurately weighed 1g sample is moistened with sufficient quantity of water
and sufficient HCl is added to get clear solution

|

By adding more water, the volume is increased to 250ml. To 50ml to this solution is added
100ml of water. Its PH is adjusted to 12 with 15ml of freshly prepared IN NaOH solution.

|

Add 40mg of murexide and 3ml of naphthol green. Titrate with 0.05M EDTA solution until a
deep blue colour is obtained.

Na*OOCH2C CH2COONa*

\ oO

Ca2* + N-CH2-CH2-N

HOOCCH2 CH2COOH

Disodium edetate

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MePoecrac cHpcoones

ww
\ /\ \

Ca- EDTA Complex

Uses:

e It also finds use internally as an antacid.

e Itisa rapidly acting non-systemic antacid

DESENSITIZING AGENTS

“+ Teeth are somewhat sensitive to heat and cold. Especially during teeth decay (or)
toothache. The perception of heat and cool has been felt strongly.
“+ Desensitizing agents are used in dental preparation so as to reduce sensitivity of teeth to

heat and cold.

“+ The exact mechanism is not know. They probably act as local anaesthetic

Eg.

Ammonical Silver nitrate solution, Formaldehyde, Liquified phenol, Zinc chloride 80%

solution, Strontium chloride.

Molecular Formula: SrClz.6H20 Molecular Weight: 266.6 g
Method of Preparation:

It is prepared by adding strontium carbonate to hydrochloric acid until effervescence gets
ceased. The solution is filtered, concentrated and allowed to crystallize.

SrCO3+ 2HCl ———————> SrCh +H20 +CO> 4

Properties:

e It forms colourless crystals (or) white granules. It effloresces in dry air.
e It is soluble in water and alcohol.

Uses:

e It acts as desensitizing agent in dental remedies.
e It occasionally finds use in medicated dentifrices, usually as a 10% w/w tooth paste, to
relieve dental hypersensitivity.

Zinc eugenol cement

>» Zinc oxide -Eugenol (ZOE) is a low strength bite resistance base used as a
temporary cement filling. It is a material prepared by combination of zinc oxide
and Eugenol contained in oil of cloves.

> It has been extensively used in dentistry since 1890’s. The ZOE cement is
available as a powder, liquid and two paste systems.

» Following reactions occur during setting
ZnO +H20 — Zn (OH)
Zn(OH)2 + 2H* Eugenol ——» Zn-( Eugenolate)z2 + 2H2O

The chelate (Zinc Eugenolate) formed is an amorphous gel that tends to crystallize imparting
strength to the set mass.

Chemical composition of Zinc eugenol cement

Components Appoximate (W/W % ) | Functions

Zinc oxide 69% Principle ingredient

White Rosin 29.3% . To reduce the brittleness
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of set cement and to

maintain homogencity
Zinc Acetate 1.0% Accelerator, Improve
strength
Zinc Stearate 0.7% Accelerator, Plasticizer
Eugenol 85% React with zinc oxide,
act as anaesthetic
Olive oil 15% Plasticizer

Classification of Zinc eugenol cement (ZOE)

Type | ZOE: For temporary cementation

Type 2 ZOE: Permanent cementation

Type 3 ZOE: Temporary filling and thermal base

Type 4 ZOE: Cavity liner

Uses:

e Itis used for temporary and permanent cementation

It is used for temporary filling, pup capping agent and cavity liner.

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UNTT-HT
3. GASTROINTESTINAL AGENTS

INTRODUCTION

e The digestive system is the (GIT) which is a group of organs. It extends from the
esophagus to the anus. Thus entrance to the system is the buccal cavity.

e The main portion of GIT include the stomach, the small intestine ( Duodenum,
jejunum and ileum ) , the large intestine ( Caecum, ascending, transverse and
descending colons ) and the rectum the exit anus.

Stomach

Duodenum

Jejunum

lleum
Caecum

STOMACH:

In stomach, digestion of protein in acidic medium takes place with pepsin enzyme. Both
acid (HCI) and enzyme are secreted in the stomach by specialized cells.

SMALL INTESTINE:
In small intestine, the following changes take place
“+ Digestion of protein takes place in alkaline medium in the presence of enzyme.

“+ Digestion of carbohydrate and lipids take place in the presence of enzymes and
bile salts.

“* Absorption of foods, Vitamins and minerals take place.
Whenever the above functions go wrong, there occur diseases (or) undesirable conditions.

Whenever inadequate secretion of acid takes place in the stomach, this causes
“Achlorhydria (or) Hypochlorhydria’”’

Whenever excess secretion of acid takes place in the stomach, this causes
“Hyperacidity (or) Wwew.remixeducation.in
There may occur accumulation of toxic substances or gases.

There may occur insufficient peristaltic movement of large intestine thereby causing
*’Constipation”’

There may occur inadequate absorption of fluids and minerals from large intestine ,
thereby causing ‘’Diarrhoea’”’

There may occur inadequate secretion of saliva, thereby making the food to swallow
with difficulty.

3.1 ACIDIFIERS

«+ These are the drugs which are able to increase the acidity in gastrointestinal tract. Some
of these drugs are used to increase metabolic acidosis where as some of these are used to
increase the gastric Hydrochloric acid.

“+ Mainly there are four types of acidifiers

Acidifiers

Gastric acidifiers Urinary acidifiers Systemic acidifiers Acids
(Sodium Phosphate, NHaCl) dil.Hcl

Gastric acidifiers:

These are the drugs which are used to restore temporarily the acidify of the
stomach in patients suffering from achlorhydria (or) hypochlorhydria. Such
patients can be treated by administration of hydrochloric acid.

Urinary acidifiers:

These are the drugs which are used to render acidic urine to enable treatment of
some types of urinary tract disorders.

Systemic acidifiers:

These are the drugs which are able to neutralize the alkaline body fluids,
particularly blood, in patients who are suffering from systemic alkalosis. Eg.
Sodium Phospahte, Ammonium chloride.

Acids

These are used as Pharmaceutical aids in the preparation, Laboratory quality
control, etc

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Ammonium chloride

Molecular Formula: NH,Cl
Molecular Weight: 53.49 g

Synonyms: Ammonium muriate, Amchlor,Salmiac
Method of Preparation:

i. Commercially, it is prepared by neutralizing ammonia with HCl. The solution is
evaporated till crude, or crystalline mass of ammonium chloride is obtained.

NH3 + HCl ———~* NH4Cl
The crude salt is purified either by crystallization or sublimation.

iii Ammonium chloride is also produced by heating ammonium sulphate with sodium
chloride

2NaCl + (NH4)2S04. ———> 2NH3 + 2HC1 + Na2S04
NH3 + HCl ————~> NH«Cl

Properties:

° It is a white, fine or coarse crystalline powder.

° It is odourless. It is having a cooling saline taste. It is slightly hygroscopic.

Assay: (Precipitation titration by using the modified Volhard’s method

Weigh accurately 0.2gm ammonium chloride in 40ml distilled water , 3m1 of nitrobenzene ,
nitric acid and 0.1N AgNO3 solution 30ml. Shake Vigorously for one minute and titrate with 0.1N
ammonium thiocyanate using ferric ammonium sulphate as the indicator.

Nitrobenzene is used for this assay 1s to avoid the interaction between the precipitated silver chloride
and ammonium thiocyanate.

NHsCl + AgNO; ————> Agel} + NHUNO;
AgNO3 + NHsSCN ——» AgSCN + NHiNO3
Silver nitrate Ammonium Silver
thiocyanate thiocyanate
NHuSCN + FeNHa (SOa)2 ————» Fe(SCN)3 + 2(NHa)2SOx
Ferric thiocyanate

(Red colour)

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Uses:

° It is used as expectorant, Diuretic and systemic acidifier.

Dilute Hydrochloric Acid

Molecular Formula: HCl

Molecular Weight: 36.5 g
Synonyms: Muriatic acid, Spirit of salt
Method of Preparation:

Ingredients:
Hydrochloric Acid ———————— 274.0 g
Purified Water —————————– 726.0 g

Hydrochloric acid (274.0g) is added gradually to water (726.0g) and mixed.

Properties:

1) It is colorless liquid. It is strongly acidic and has about 1.04 to 1.05 specific
gravity.

2) Hydrochloric acid combines directly with alkalis such as ammonia and sodium
hydroxide. These are known as neutralization reactions.

NH3 + HCl] ——~> NHacl

NaOH + HCl ———> NaCl +H20

3) It gives a curdy white precipitate with silver nitrate.

AgNO3 +HCl ———~> AgCl v + HNO3

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4) It releases carbon dioxide from carbonates and bicarbonates.

Na2C0O3 + 2 HCl —— > 2NaCl+H2C0O3

H2CO3 ———> H20+ CoO?“

NaHCO3 +HCl ———~> NaCl + CO2 x H20

Uses
° Hydrochloric acid is used in the cases of ‘achlorhydria’ ( lack of hydrochloric acid
in the gastric juice). The dose is 0.6 to 8ml(I.P)
° It is also used as a reagent in the laboratory.

3.2 ANTACIDS

These are the drugs which are usually alkaline substances and used for neutralizing excess
acid in the stomach of patients suffering from hyperchlorhydria (hyperacidity). These drugs

give relief of pain due to hyperchlorhydria. It is possible to measure the efficacy of antacid in

terms of neutralizing capacity.

Antacids act on gastrointestinal tract after being converted into soluble salts by hydrochloric
acid. The cations such as calcium, aluminium, etc., are having constipating effect whereas
that of magnesium in having laxative effect because of this reason, combination of calctum-
magnesium ( or ) aluminium-magnesium salts are generally employed as antacids. These

combination help in overcoming constipative effect of aluminium and laxative effect of

magnesium.

QUALITIES OF AN IDEAL ANTACID
** It should be insoluble in water and has fine particle form.
** It should not be absorbable (or) cause systemic alkalosis.
** It should be able to exert its effect gradually and over a long period of time.

** It should be stable and readily available.

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“+ The reaction between antacid and gastric HCl should not produce large volume of
gas.

“* The antacid should buffer in the P# 4 to 6.

** The antacid should probably inhibit pepsin, the proteolytic enzyme.

CLASSIFICATION OF ANTACID

Antacids may be classified as
Classification of Antacids:

1. Systemic Antacid

2. Non systemic Antacid

a) Aluminium containing antacids
b) Calcium containing antacids

c) Magnesium containing antacids

d) Combination antacid preparation

1. Systemic(absorbable) antacids:

These are soluble, readily absorbable and capable of producing systemic electrolytic
alteration and alkalosis.

Eg; Sodium bicarbonate.

2. Non systemic(non-absorbable) antacids:

These are not absorbed to a significant extent and thus do not exert an appreciable systemic
effect. This group if further sub-divided into following.

a) Aluminium containing antacids:

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b)

c)

d)

Examples are aluminium hydroxide, aluminium phosphate, dihydroxyaluminium
aminoacetate, dihydroxyaluminium sodium carbonate gel.

Calcium containing antacids:

Examples are calcium carbonate, tribasic calcium phosphate.

Magnesium containing antacids:

Examples are magnesium carbonate, magnesium citrate, magnesium hydroxide,
magnesium oxide, magnesium phosphate, magnesium trisilicate.

Combination antacid preparation:

Examples are aluminium hydroxide gel and magnesium hydroxide, aluminium
hydroxide gel and magnesium trisilicate, Magaldrate (monoalium hydrate; hydrated
magnesium aluminate), Simethicone (defoaming agent) containing antacids, calcium
carbonate containing antacids mixture.

Preparation Containing Combination of Antacid

e Many preparations which are having combination of antacid are being
marketed. The idea behind such combination is to counteract the constipative
action of calcium and aluminium containing antacids with laxative effect of
magnesium containing antacid.

e The antacid are combined with Simethicone type of compounds which are
having antiflatuluent action as they are antifoaming agents and cause
dispersion of gases. Few such combination are reported to be official in B.P.

Combination preparations

Some combination preparations are as follows;

Aluminium hydroxide magnesium carbonate co-dried gel:

It is a co-precipitate of aluminium hydroxide and magnesium carbonate carefully
dried to contain a critical proportion of water for antacid activity. It acts as an antacid
that is given in doses of up to lg.

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Algicon Tablets:

The tablets are chewable, prepared by aluminium hydroxide-magnesium carbonate
co-dried gel(360mg), Magnesium alginate(500g), Magnesium carbonate(320mg) and
potassium bicarbonate(100mg).

The suspension is prepared by combining aluminium hydroxide-magnesium
carbonate co-dried gel(140mg), Magnestum alginate(250g), Magnesium
carbonate(175mg) and potassium bicarbonate(50mg/5ml). Dose : 1 to 2 tablets or 10
to 20ml of suspension after meals and at bedtime.

Simeco Tablets:
The tablets contain aluminium hydroxide-magnesium carbonate co-dried
gel(282mg), magnesium hydroxide(85mg) and activated dimethicone(25mg).
4. Aluminium Hydroxide gel-Magnesium Trisilicate Combinations:

This is one of the more common combinations. It has laxative, Constipative and
protective effect.

5. Magaldrate:

It is a chemical combination of aluminium hydroxide and magnesium hydroxide.It
contains the equivalent of 28 to 39% magnesium oxide and 17 to 255 of aluminium
oxide.

6. Calcium Carbonate Containing Antacid Mixtures:

Calcium carbonate with aluminium hydroxide gel yields products which have a rapid
onset with prolonged action. Three part combinations of calcium carbonate,
Aluminum hydroxide gel and a magnesium containing actacid are also available.

7. Alginic acid Sodium Bicarbonate-Contaning Antacid Mixtures:

The tablet is chewed when the contents come in contact with water. The alginic acid
reacts with sodium bicarbonate, forming sodium alginate and carbon dioxide.In the
acid environment of the stomach,alginic acid is precipitated in the form of a light,
viscous gel which floats on top of the stomach contents.

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Sodium Bicarbonate

Molecular Formula: NaHCO;
Molecular Weight: 84.01 g
Synonyms: Sodium hydrogen carbonate, Baking soda

Method of Preparation:

It is prepared by passing CO2 gas through a solution of sodium hydroxide. The

solution is concentrated to get the product.

2NaOH + CO2 —* NarCO3 + H20

Na2CO3 + H20 + CO2 ————> 2 NaHCO3

Assay: (Acid — Base Titration)
Principle:

It is assayed by acidimetric acid-base titration. Sodium bicarbonate in aqueous solution is titrated
with 0.1M hydrochloric acid using methyl orange as indicator, the end point is the appearance of faint
pink colour.

2NaHCO; + 2HCl-——————> 2NaCl + 2HO + 2C0,’S
Procedure:

Weighed accurately 0.15g of sodium bicarbonate into a conical flask and dissolve 50ml
of water, titrated with 0.1M hydrochloric acid using methyl orange as an indicator until faint
pink colour appears.

Uses:

e Mainly used for its neutralizing properties. Its aqueous solution are used as local
applicants for burns, insect bites etc.,

e It is used as electrolyte replenisher
e = Its 3.5% solution in warm water is used in eye lotion

e It 5% solution is used in ear drops for softening of ear wax.

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Aluminium hydroxide gel

Molecular Formula: Al(OH)3
Molecular Weight: 77.99 g

Standards: The preparation contains not less than 3.5% and not more than 4.4% w/w of
aluminium oxide (Al2O3).

Method of Preparation:

It is prepared by adding a hot solution of potash alum slowly with constant stirring to
a hot solution of sodium carbonate. After complete removal of carbon dioxide the precipitate
aluminium hydroxide is filtered. It is washed thoroughly with hot water until it becomes free
from sulphate ion and the precipitate is suspended in distilled water to the required strength.

3Na2CO3 + 2 KAI (SO4)2 + 3H20 ————> 3Na2S04 + K2804 + 2Al (OH) 3 V +3002

In washing the precipitate of aluminium hydroxide hot water but not boiling water should
be used because of decompose the aluminium hydroxide

Properties:

° It is white viscous suspension
° A clear liquid gets separated when it is kept standing for some times
° Aluminium hydroxide gel gives astringent aluminium chloride when it reacts

with gastric hydrochloric acid. This results into nausea, vomiting and constipation.

Al (OH)3+3HCl_ ———> AICh + 3H20

Test for purity:

Acid Neutralising capacity of Aluminum hydroxide gel

Principle:
Aluminium hydroxide reacts with hydrochloric acid to form aluminium chloride. This

means that aluminium hydroxide can act as a good antacid and will be able to neutralize the acid

in the stomach.

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Acid neutralizing capacity of aluminium hydroxide gel is determined by allowing the gel
to remain in contact with 0.1IM HCl at 37°C in a thermostatically controlled water bath and
measuring the pH at successive time intervals. Finally the concentration of the acid is increased
further and the neutralizing capacity of the gel is found out by determining the remaining acid by

titration with 0.1 M sodium hydroxide after one hour.

Aluminium hydroxide reacts with HC] to form aluminium chloride.

Al(OH); + 2 HCI ————— AICl +3 H2O

Procedure:

5 g of Aluminium hydroxide gel was dispersed in 100 ml of water, heat to 37°C ina
thermostatically controlled water bath, and 100 ml of 0.1 M HCI previously heated to 37°C was
added. It was stirred continuously and the temperature was maintained to 37°C. The pH of the
solution at 37°C at 10, 15, 20 min were measured and the pH was not be more than1.8 after 10
mins, 2.3 after 15 mins and 3 after 20 mins. At any time the pH was not be more than 4.5.

10 ml of 0.5 M HCl previously heated to 37°C was added and stirred continuously for
maintaining the temp at 37°C for 1 hr and was titrated with 0.1 M NaOH till a pH was attained to
the pH 3.5.

Observation:
Less than 50 ml of 0.1 M NaOH was required for the titration.

Report:
The sample of Aluminium hydroxide gel is standard as per IP.

Uses:

e Aluminium hydroxide gel is very effective slow-acting antacid.
Al (OH) 3 +3Hcl ———> AIC + 3H20

e It does not get absorbed in alimentary canal and does not produce CO2. It is widely used
in treatment of intestinal toxemia and hyperchlorhydria.

e Itis able to neutralize gastric hydrochloric acid and causes absorption of toxins, and gases.

e It does not cause any systemic alkalosis.

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Magnesium hydroxide Mixture

Molecular Formula: Mg (OH) 2
Molecular Weight: 58.32 g

Synonyms: Milk of Magnesia, Magnesium hydroxide oral suspension.

Method of Preparation:

The magnesium hydroxide obtained in the preparation of milk of magnesia is evaporated to

dryness.

Light magnesium oxide is mixed with a solution of sodium hydroxide to form a smooth
cream and purified water is added to further diluted it. This suspension is then poured into a
solution of magnesium sulphate with continuous stirring, Magnesium hydroxide is
precipitated. It is allowed to settle down, the supernatant liquid is decanted and the residue
is washed with purified water on a calico strainer till the filtrate dried.

MgO + H20 ——> Mg (OH) 2

MgSOq4 + 2NaOH ———> Mg (OH) 2 + Na2SO4

Properties:

It is white fine amorphous powder; it is almost insoluble in water yielding
a solution which is slightly alkaline. It dissolves in dilute mineral acids.

It is used as an antacid and osmotic laxative
It is used as an alkaline mouth wash.

5 to 10 ml as an antacid
15 to 30 ml as an laxative

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3.3 CATHARTICS

Cathartics are the agent that promotes the evacuation from the bowel. It facilitates the
passage and elimination of the feaces from the intestinal tract through the colon and
rectum.

Laxative ————» The term is used for mild cathartics
Purgative ————_» __ The term is used for strong cathartics

Cathartics may be defined as those drugs which bring about defecation. They are beneficial in
constipation and for expulsion of intestinal parasites. They may also be given for clearing bowels
before surgery.

Laxative, cathartics and purgative act by retaining of fluid in the bowel. These may be
administered by oral route (by powder or suspension) or by rectal route (enema or supposito

Cathartics or purgatives generally act by four different mechanisms.
i. Stimulant purgatives
iii Bulk purgatives
iii. Lubricants

iv. Saline cathartics

i. imul rgati
These are the drugs or chemicals which act by local irritation or intestinal tract and
bring about stimulation of peristaltic activity.

Eg:

Senna , Rhubarb , Cascara , Podophyllum , Castor oil , Aloe , Bisacodyl

li. Bulk purgatives:

These are the agents which are able to increase bulk of intestinal contents.
Eg:

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Bulk purgatives are methyl cellulose, sodium carboxy methyl cellulose,
Gum , ispagol, etc

Lubricants:

In constipation, contents of intestine become hard because of absorption of water
by body, there results difficulty in clearing of bowels.

Eg:

Liquid paraffin, glycerin, mineral oil etc., as lubricants and cause smooth clearance
of the fecal material.

lin harti

These act by increasing the osmotic load of intestine by absorbing large quantity of
water and thereby stimulate peristalsis. Poorly absorbable cations like calcium,
magnesium and anions like phosphate, sulphate, and tartrate are contributing to this
effect.

The saline cathartics are water soluble mainly inorganic chemicals and they are taken
with plenty of water.

The saline laxatives are relatively free from side effects when taken for brief periods.
Patients on low sodium diet should not use the sodium containing saline laxatives.

These cathartics are in the form of suspension, tablet or in other suitable formulations.
Their action is mainly attributed to their osmotic property in intestinal limen

Eg:
Magnesium hydroxide, Magnesium sulphate and tartarate salts of sodium and

Potassium.

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Magnesium sulphate

Molecular Formula: MgSOq. 7H20

Molecular Weight: 246.32 g
Synonym: Epsom salt

Method of Preparation:

i. It is obtained by the action of dil.H2SO4 on magnesium carbonate or
magnesium oxide or from native carbonate.

MeCO3 + H2SO4 ——> MgSOu4 + H20 + COr*

The solution is filtered. The filtrate is evaporated to crystallization.

ii. It is manufactured by the action of sulphuric acid on the native carbonate ( magnesite)
or on previously calcined dolomite. When dolomite is used, magnesium sulphate
passes into solution, and sparingly soluble calcium sulphate gets deposited.

MgCO3.CaCO3 + 2H2SO04 ———> MgSO4 + CaSO4 + 2CO2 + 2H20

The liquid is filtered and the filtrate is evaporated to crystallization.

Properties:

e It occurs as colourless crystals having a cool, saline bitter taste.
e It effloresces in warm dry air.
e When heated gently, it loses most of its water and converted to monohydrate(White

powder),
MgsO4.7H20 = ——————>__ Mgs0q.H20
Magnesium Magnesium
Sulphate Sulphate
(heptahydrate) (monohydrate)

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Uses:

e Magnesium sulphate is given orally in dilute solutions. About 5g ( which is
40 milliequivalent of Mg?” ) gives rise to laxative effect.

e Itis given with fruit juices because of bitter and nauseating taste.

Mechanism of action:

Magnesium sulphate does not get absorbed from intestinal tract and thus retains
sufficient water within the lumen. The hydrostatic pressure is able to promote motor
activity or peristalsis.

Dose:
10-15¢
Contraindication;

It is to be used with care in patients with impaired renal function.

Sodium Orthophosphate

Molecular Formula: NasHPOs.12H20

Molecular Weight: 358.14 g
Synonym: Disodium hydrogen phosphate (or) Secondary sodium orthophosphate.

Method of Preparation:

It may be obtained by adding sodium carbonate to a hot solution of phosphoric acid.
Sodium carbonate fails to affect the third hydrogen of phosphoric acid and causes the
formation of disodium hydrogen phosphate

H3PQ4 + NaxCO3_———> NagHPO4 + H20 + CO? “

The solution is neutralized, concentrated and the crystals are separated out by
centrifuging, washed and dried.

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It is also obtained from calcium phosphate which on being treated in correct
proportions with sulphuric acid, Yields calcium phosphate; the former is precipitated
while the latter remains in solution.

Ca3 (PO4)2 + 2H2SO4 ———~> Ca(H2PO4)2 + 2 CaSO4 v

The above mixture after the addition of boiling water if filtered. Now the filtrate is
treated with sodium carbonate when dibasic calcium phosphate gets deposited leaving
sodium phosphate (Disodium hydrogen phosphate) in solution. The reaction may be
put as follows

Ca(H2PO4)2 +NazCO3 ———> CaHPO4 +NasHPO4 +CO2 “+ H20

The solution is filtered off. The crystals of sodium phosphate are obtained by
concentrating the solution and ultimate crystallization.

Properties:

° It occurs in the forms of colourless transparent crystals, having a saline taste.

° It is odourless and strongly effloresces in air. It is soluble in water but
insoluble in alcohol.

° On heating over 300°C it is converted into sodium pyrophosphate.
2Na2HPO4 ————> NagP207 + H20

300°C

e It is used as a saline laxative It is also used as a cathartic and buffering agent.
e It is widely used as cathartics due to poor absorption of HPO.*

e It is used to treat constipation or to clean the bowel before a colonoscopy

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e Inthe form of oral solution, it is also used as anti-hypercalcemic.

Kaolin

Molecular Formula: AlcO3.2Si02.2H2O
Molecular Weight: 258 g
Synonym: The China Clay, Hydrated Aluminum silicate

Method of Preparation:

It is a hydrated aluminium silicate, widely distributed in nature. It is prepared when the rock is
mined, executed, the impurities are washed with the flow of water and then powdered.

Kaolin is found in two form Heavy Kaolin and Light Kaolin. Therefore the rock is
elutriated with water and large sized particles are separated. The turbid liquid is allowed to settle;
heavy kaolin containing large particles and colloidal kaolin containing particles of small size are
separated and dried.

Properties:

e It is white fine powder.

e It is odourless and tasteless.

e It is insoluble in water and mineral acid.

e It is fusion point range between 1700 — 1800°C.
e On heating kaolin loses water molecules.

e It is decomposed by prolonged boiling or treatment with concentrated sulphuric acid.

1. Kaolin is used as adsorbent, antidiarrhoeal and increases the bulk of faeces.
2. Kaolin adsorbs toxins from alimentary tract and is thus beneficial in diarrhoea.
3. Kaolin has also been used in the treatment of chronic ulcerative colitis.

4. Externally, heavy kaolin has some use as poultice, dusting powder, foot powder and as an
ingredient of toilet preparation.

5. It is also used as filtering medium as well as clarifying and decolorizing medium.

6. Sometimes it is also used as tablet diluents.

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Bentonite

Molecular Formula: AlzO3.48i02.H20
Molecular Weight: 422.286 g
Synonym: Clay

e Bentonite is a name given to particular clay that was originally found in fort Benton. It is
native colloidal hydrated aluminium silicate, freed from gritty particles. It occurs
naturally.

e Bentonite is an aluminium silicate having SiOz, AlzO3, FexO3, CaO, MgO and some
sodium and potassium.

Properties:

1. It occurs as a very fine, pale buff or cream coloured powder.
2. It is free from grit
3. It is odourless and has slightly earthy taste.

4. It is insoluble in water but it swell to about twelve times its volume when added to water.
It neither dissolves nor swells in organic solvents.

Test for purity:
Swelling power of Bentonite.

Principle:
When water is added to bentonite, each particle is surrounded by a layer or shell of water.

This produces a particle several times larger than the original particle i.c swelling of mass results.
Bentonite can absorb 5 times its weight of water and its bulk may increase by 12 — 15 times.
Bentonite is insoluble in water but swells into a homogenous mass.

To find out the swelling power, the sample is added in small quantities at intervals of 2
minutes to a solution of Sodium Lauryl Sulphate in a 100ml measuring cylinder. It is allowed to
stand for 2 hours. The apparent volume of the sediment should not be less than 24ml. the
presence of the wetting agent (Sodium Lauryl Sulphate) promotes capability between the

insoluble bentonite and water.

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Procedure:

1) 1 g of Sodium Lauryl Sulphate (SLS) was dissolved in 100 ml of distilled water and
transferred to a 100 ml graduated or measuring cylinder having a diameter of 3 cm.

2) 2 gm of sample (bentonite) was weighed accurately and was added in small quantities (20
portions) at interval of 2 minutes and allow each portion to settle before adding the next.

3) It was set aside for 2-hours

4) The apparent volume of the sediment at the bottom of the cylinder was found out.

Observation:
The apparent volume of the sediment was Less than 24 ml.

Report:
The given sample passes the test

Uses:
1. It is used as Cathartics due to its amazing absorption properties.
2. It can remove toxic metals and chemicals following radiation treatments.
3. Promotes healthy bacteria balance and detoxify the digestive system.
4. It also supports in liver detoxification.
5. As an antidote, it is used in mercury poisoning.
It is helpful in removing the internal parasites from digestive system.
It also helps in colon cleansing
8. It supports in boosting immune system.

9. As a pharmaceutical aid, it is also used as a binder, if chemically compatible with other
ingredients.

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3.4 ANTI MICROBIALS

These are the agents which are used to destroy of inhibit the growth of pathogenic micro-
organisms. They are of six types and their mechanism of action is given below

1.

Antiseptics:

These are substances that are able to kill or prevent the growth of micro-organisms. This
term is specific for preparations which are to be applied to living tissue.

Disinfectants:

These are the substances that prevent infection by the destruction of pathogenic
microorganisms.

Germicides:

These are substances which kill micro-organisms. More specific terminology like
‘bactericide (against bacteria), fungicide (against fungi), Virucide (against virus) etc.
denotes exact action.

Bacteriostatics:

These are substances which primarily function by inhibiting the growth of bacteria. Thus ,
bacteriostatic drugs or agents do not kill but arrest the growth of bacteria.

Sanitizers:

These are the disinfectants used to maintain public health standards and called as
sanitizers. Sanitation is mainly concerned with cleaning or washing away the organism.

Sterilization:

Sterilization is the process of complete destruction of all living microorganisms,
including bacterial spores, it can be done by physical methods (application of heat or
radiation) or by chemical means (use of chemical disinfectant).

Mechanism action of antimicrobial agents:

The mechanism action of antimicrobial agents may range from a mild astringent to powerful
oxidative processes.

Inorganic compounds generally exhibit antimicrobial action by involving either of the
following three mechanisms

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1.

1. Oxidation mechanism
2. Halogenation mechanism

3. Protein binding ( or ) Precipitation mechanism

Oxidation mechanism

Compounds acting by this mechanism belong to class of peroxides of peroxyacids, oxygen
liberating like permanganate and certain oxo-halogen anions. These anti infective agents bring
about oxidation of active functional groups present in proteins or enzymes vital to the growth or
survival of micro-organisms. This causes a change in the conformation of the protein and thereby
alters its function.

aN e™N Oxidation 4 Ss ——— SN
H H

Protein Altered Protein

Eg.

A free sulfhydryl group has been essential for functioning of a variety of proteins and enzymes.
This free nature of sulfhydryl group gets destroyed by oxidation resulting into a formation of a
disulfide bond.

Halogenation mechanism

Compounds which are able to liberate chlorine or hypochlorite or iodine act by this mechanism.
This category of agents acts on peptide linkage and alter its potential and property. The
destruction of specific function of protein causes death of micro-organisms.

Most of the enzymes are protein in nature. A protein molecule is compose of a variety of
amino acids connected through a peptide ( -COONH- ) linkage . As hypo-chlorites ( -OCI- ) are
found to chlorite peptide linkage, antiseptics having hypo-halite functional groups exert their
antimicrobial activity by chlorination of peptide linkage in protein molecule.

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ocr
Amino acid C — N—— Amino acid ———» Amino acid —- C —-N— Amino acid
i cr
Protein Structure Altered Protein

. Protein Precipitation

Many metal ions exhibit protein binding (or) protein precipitation. The nature of interaction with
protein takes place through polar group of protein which acts as ligands and metal ions as lewis
acid. The complex formed may be strong chelate giving rise to inactivation of protein. This
action in general is non-specific.

Potassium Permanganate

Molecular Formula: KMnO,
Molecular Weight: 158.03 g
Synonym: Permanganic acid.
Method of Preparation:

Potassium permanganate is prepared by mixing a solution of KOH with powdered
manganese oxide and potassium chlorate. The mixture is boiled, evaporated to yield to residue
which is heated in iron pans until it has acquired a paste consistency.

KOH + 3mnQ2 + KClO; —————» KomnO, + KCl + 3H20

Potassium manganate (green) so formed is extracted with boiling water and a current of chlorine,
CO2 (or) ionized air is passed into the liquid until it gets converted to permanganate. The
manganate formed is removed continuously so as to prevent its breaking down to the manganate.

6K2mnO4+ 3Cl, —————» _ 6Kmn0O, + 6KC1

When carbon dioxide is passed through the solution in place of chlorine, only two-third of
manganate gets converted into potassium permanganate. One third is converted into manganese
dioxide.

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3KamnO, + 2CO2 ——————» 2K mnOz + mnOet 2K2CO3

The solution of potasstum permanganate is drawn off from any precipitate of mnO2 which is
then concentrated and crystallized. The crystals are then centrifuged and dried.

Properties:

It occurs in the form of dark purple coloured monoclinic prisms
It is soluble in 15 parts of water and 3.5 parts of boiling water.
A solution of potassium permanganate is having a sweetish, astringent taste.

When it is a heated, it decomposes at a high temperature (240°C )

2KmnO4 ————+» KomnO, + mnO2+ O2 4

When hydrogen sulphide gas is passed through potassium permanganate solution which
is acidified with HCl, the violet colour is disappears and sulphur gets precipitate.

2 KmnO, + 6HC1 + 5H2S —————» 2mnCh+ 2KC1 + 5S ¥+ 8H20

When a solution of hydrogen peroxide is added to an acidified potassium permanganate
solution, the colour of the permanganate solution gets discharged.

2 KmnOsz + 3H28O4+ 5H202. ————_ K2804+ 2mnSO4+ 8H20 + 502

When HC1 is added to solution of potassium permanganate, chlorine gas gets produced.

2 KmnO«+ 16HC] ————» 2KC1 + 2mnCh + 8H20 + 5Ch 4

Alkaline (or) neutral solution of potassium permanganate is able to oxidize iodide to
iodate.

2 KmnO, +H20+ KI —————» 2mnO2+ 2KOH + KIO3

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Uses:

e It finds use as an antiseptic, in mouth wash and in cleaning Ulcer or Abscesses.

e It finds use as an antidote in case of poisonings by barbiturates, chloral hydrates, many
alkaloids etc.

e Inveterinary practice it has been very much used as an antiseptic.

BORIC ACID

Molecular Formula: H3BO3
Molecular Weight: 61.83 g

Synonym: Boracic acid, Orthoboric acid

Method of Preparation:

Boric acid is prepared from native borax and from borates by reacting them with hydrochloric
(or) sulphuric acid. In the laboratory, boric acid is obtained by adding a mixture of conc.H2SO,
and water (1:5) to a boiling solution of borax (60g in 160ml of water).

NazB4zO7 + H2SOut 5H20 ———» _NaSO, + 4H3BO3

The solution is filtered and kept aside for crystallization. The crystals of boric acid are separated
and then washed until they becomes free from sulphate ions, finally, they are dried at room
temperature.

Properties:

e Colourless, odourless white powder.
e It is odourless with slightly acidic and bitter taste

e Boric acid is a weak acid. Heating orthoboric acid to certain temperature, yields various
dehydration products.

e Boric acid on heating to 100°C loses one molecule of water, to give meta boric acid
(HBO?)

100°C
H3BO3 =——_¥——»HBO: + H20

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e Heating to still higher temperatures tetra boric acid produces the anhydride of boric acid,
boron trioxide (B2O3), which is having a glassy appearing solid.

ZN
H2B,07 |©————»2B203 +H20

160°C

Uses:

e Boric acid is a local-infective and is used in dusting powders, local antiseptic creams,
ointment, lotions etc. applied to skin or mucous or eye.

e Aqueous solutions have been used as mouth washes, eye lotions, skin lotions.

e It possesses weak bacteriostatic and fungistatic properties.

Hydrogen Peroxide
Molecular Formula: H202
Molecular Weight: 34.01 g

Method of Preparation:

i. It is obtained by adding a thick paste of barium peroxide in ice cold water to a calculated
quantity of ice cold dilute sulphuric acid. The insoluble barium sulphate is filtered off.

BaO2 + H28SO4 —————» BaSOu¥ + H202

ii. It is also obtained by decomposing barium peroxide with phosphoric acid or by passing
CO> through a suspension of barium peroxide in water.

3BaQ2 + 2H3PO, ————» Ba(POs)2 + 3H202

BaOz2 + H20 + CO2 = ———» H202 + BaCO;

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Properties:

Hydrogen peroxide is stable in solution of high purity. However , it decomposes rapidly
in alkaline solutions or under catalytic influences such as copper, iron or manganese ions.

2H202_ —————» 2H20 + O2 4

Hydrogen peroxides in aqueous solution ionizes to give the peroxide ion.

H:02 {= 2H + Or

Potassium permanganate in acid solution is rapidly reduced. Here hydrogen peroxide acts
as a reducing agent.

2KMnOy + 3H2SO,+ 5 H202 —————» K2SO,4 + 2MnSO, + 8H20 +502 4

Assay: (Oxidation-Reduction( Permanganometry))

Hydrogen peroxide and acidified potassium permanganate, both are oxidizing agents. These two
oxidizing agents reduce one another with the evolution of gaseous oxygen. Hydrogen peroxide
reduces KmnOx, solution and causes its decolouration. At the end point, excess drops of KmnO,
gives pink colour. Potasstum permanganate itself acts as an indicator.

The assay of H2O2 is carried out by the permanganate method. 10ml of the sample is diluted to
250ml in a volumetric flask with purified water. To 250ml of this solution, 1Oml of 5N H2SOsg is
added. The, the contents are titrated with 0.1N KmnO, solution, until a faint pink colour is
obtained.

2KmnO, + 3H2SO4 + 5H202, —————» K2SQO,q + 2mnSO, + 8H20 + 502

Uses:

It acts as an antiseptic and a germicide and hence is used for cleaning cuts and wounds.
It is an effective antidote for phosphorous and cyanide poisoning.

It also finds use for cleaning ears and removing the surgical dressings.

It finds use as a germicide and deodorant.

It is also used for removing ear wax

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Chlorinated Lime

Molecular Formula: Ca (OCI) Cl, CaOCle
Molecular Weight: 136.98 g
Synonym: Bleaching Powder, Chloride of lime

Method of Preparation:

Chlorinated lime is a compound which is obtained by the action of chlorine on calcium
hydroxide. Slaked lime is spread on shelves in a suitable container. Then, the chlorine gas is
introduced at the top of the chamber and then allowed to pass through the contents of the shelves.
This is usually carried out at 25°C , thereby minimizing the formation of calcium chloride.

Ca(OH)2 + Clk ————» Ca(OCl)Cl + H20

Properties:

e It occurs as a dull white powder having a characteristic odour, when exposed to air, it
absorb moisture and gradually decomposes.

Assay: ( Oxidation — Reduction (Iodometry)

Principle:

The assay is carried out on the basis of the oxidation-reduction reaction. In the presence of acid
the available chlorine is liberated from chlorinated lime, Available chlorine may be defined as
the chlorine that is liberated from a substance by acids. The free chlorine reacts with potassium
iodide to liberate iodine quantitatively and the quantity of iodine set free is determined by
titration with 0.1N Sodium thiosulphate.

Ca(OC]Cl + 2CH3COOH—————» Ca(CH3COO)2 + HOC] + HCl
Hypochlorous acid
HOC] +HCl + 2KI ———————» 2KC1 + Ib + HO
In + 2Na2S203 ————_________» Na2SsOg + 2Nal
Sodium thiosulphate Sodium tetra thionate
Procedure:

4¢ of the bleaching powder is triturated with successive small quantity of water. This is
transferred to a one liter flask and the volume made upto the mark. A measured volume
(100ml) of the suspension is taken in a iodine flask.

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Uses:

Then, it is treated with an excess of potassium iodide solution(3g), acidified with 5ml of
acetic acid, shaken for 2-3 minutes and kept aside for 15 minutes and the liberated iodine
is titrated with 0.1N Na2S20s3 solution till the deep iodine colour changes to yellow colour.
At this stage, few drops of starch solution are added to the iodine flask. End point is
disappearance of blue colour.

Its main uses have been due to its disinfecting and bleaching properties.
It is also used as an ingredient in the preparation of detergents.

It is powerful bleaching agent and is used in decolorizing most dyes.

Iodine

Molecular Formula: Ib

Molecular Weight: 126.9 g
Method of Preparation:

Iodine is manufactured by extracting (Seaweed’s ash) with water. The solution is
concentrated when the sulphate and chloride of sodium and potassium get crystallized out,
leaving freely soluble sodium and potassium iodide in the mother liquor. Sulphuric acid is
added to the mother liquor and sulphur, which gets liberated, from small amounts of
thiosulphate and sulphide, is allowed to settle down. The mother liquor is decanted, and to
this mnoz is then added and the iodine distils over.

2Nal + 3H2SO4 + MnO2 ————» MnSOs + 2NaHSOs + Ib + 2H20

Properties:

Iodine is a heavy, bluish-black, rhombic prism or plates having a metallic taste.
At higher temperatures, the density of iodine decreases as it dissociates.

It is insoluble in water but soluble in alcohol. It is freely soluble in chloroform and
aqueous solution of iodides.

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Uses:

It reacts directly with some non-metals and with many metals.

2P + 31, ———»>_ 2PIz

Fe + I, ————_ > Felo

Reducing agents reacts with aqueous solutions of iodine and are oxidized.
In+ 2Na2S203 —————> NarSu0c6 + 2Nal

Potassium iodide is able to dissolve large quantities of iodine due to for motion of iodates
ion.

KI+ bk —=——— KI

Iodine finds use in medicine mainly as a counter irritant and disinfectant.
It is used as local germicide.

Proper thyroid functioning iodine is supplied to the body either in the elemental form or
in the form of sodium or potassium iodide.

Elementary iodine is highly toxic and the starch and sodium thiosulphate are useful
antidotes.

Official Preparation Of Iodine

i.

Povidone-Iodine Solution

Povidone — iodine solution is an aqueous solution of povidone — iodine. It is a complex produced
by the interaction between iodine and povidone ( polyvinyl pyrrolidine ). The complex is having
about 10% w/v of available iodine.

Use:

It is used for disinfection of skin, mouth (or) wounds by using povidone-iodine solution.
It has been found to be also effective in the management of bums and cuts.

Povidone-iodine is available in wide variety of preparation for applications to the skin
and mucous membrane and for use as disinfectant.

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i Aqueous iodine solution

Synonym: lugol’s solution

Composition:
Iodine 50g

Potassium iodide————————– 100g
Purified water sufficient to produce—-1000m1
Use:
1. It is used to treat thyrotoxicosis prior to surgery

2. It helps to protect the thyroid gland from harmful effects of radioactive iodine and to treat
iodine deficiency.

3. When applied to the cervix, it is used in screening for cervical cancer.

Ti Weak iodine solution

synonym: Iodine tincture or Tincture of iodine
Composition:

Todine 20g
Potassium iodide————————– 25g
Alcohol(50%)—————————— 1000ml

Use:
e It is a well known and popular antiseptic , which is applied on cuts and wounds.

Iv Strong iodine solution

Iodine 100g
Potassium iodide————————– 60g
Purified water—————————– 100ml
Alcohol (50%) —————————— 1000ml

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UNIT-IV
4. MISCELLANEOUS COMPOUNDS

4.1 EXPECTORANTS

e Expectorants are the drugs that help in removing sputum from the respiratory tract
either by increasing the fluidity (or reducing the viscosity) of sputum (or)
increasing the volume of fluids that have to be expelled from the respiratory tract
by coughing.

Eg.

Inorganic expectorants are ammonium chloride, potasstum iodide, sodium
iodide and related substances.

Classification of Expectorants:

“+ It is possible to classify expectorants in according to their mechanism of action
into categories.

Expectorants

!

Sedative Expectorants Stimulant Expectorants

Sedative expectorants:

e These are stomach irritant expectorants which are able to produce their effect
through stimulation of gastric reflexes.

Eg.
Bitter drugs —————-» _ Ipecac, senega, Indian Squill.
Compounds —————» Antimony potassium tartarate, Ammonium chloride,

Sodium citrate, Potassium iodide etc..

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Stimulant expectorants:

e These are the expectorants which bring about a stimulant of the secretary cells of
the respiratory tract directly (or) indirectly.

Eg:

Eucalyptus, lemon, Anise and active constituents of oil like terpine hydrate,
anethole.

Potassium Iodide

Molecular Formula: KI
Molecular Weight: 166.00 g

Synonym: Potide, Kali iodidum

Method of Preparation:

L

il.

Industrially, it may be obtained by the action of iodine on moist iron fillings to form
ferro-ferric iodide (FeI3 (or) Fel2, 2Fel3) which then gets decomposed with potassium
carbonate.

Fe +I, ———__-_» Felz: 2Fel3
Felo: 2Fel3 + 4 K2CO3_: ———®» 8KI + FeO.Fe2CO3+ 4CO2

Ferroso-ferric oxide is filtered out. The filtrate is concentrated to get KI. The salt may be
purified by recrystallization.

Hot aqueous solution of potassium hydroxide with iodine in slight excess to form a
mixture of potassium iodide and potassium iodate. The solution is concentrated and then
treated with excess of charcoal powder followed by evaporating the mixture to dryness
followed by ignition. The charcoal (carbon) reduces the iodate to iodine, utilizing thus the
total iodine to get the potassium iodide. The product is collected with water, then it is
filtered and potassium iodide is obtained by crystallization.

6KOH + 3l2 ————> 5KI +KI103 + 3H20

KIO3 +3C ———> k1+3co#

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Properties:

e It occurs as colourless, transparent (or) opaque crystals or a white granular powder.
e Itis odourless, and is having a saline and bitter taste.

e The salt is deliquescent in moist air.

Uses:

e Potasstum iodide is used internally for supplying iodine for, treatment of thyroid
deficiency.

e It finds use as expectorant in cough mixture and also as a saline diuretic.

e It has also mild antifungal activity.

Ammonium chloride

Molecular Formula: NH4Cl
Molecular Weight: 53.49 g

Synonyms: Ammonium muriate, Amchlor,Salmiac
Method of Preparation:

i. Commercially, it is prepared by neutralizing ammonia with HCl. The solution is
evaporated till crude, or crystalline mass of ammonium chloride is obtained.

NH3 + HCl ———> NHaCl
The crude salt is purified either by crystallization or sublimation.

ii. Ammonium chloride is also produced by heating ammonium sulphate with sodium
chloride

2NaCl + (NH4)2804 ———> 2NH3 + 2HC1+Na2SO4
NH3 +HCl ————~> NH«CI

Properties:

° It is a white, fine or coarse crystalline powder.

° It is odourless. It is having a cooling saline taste. It is slightly hygroscopic.

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° Its 0.8% w/v solution is isotonic with serum.

Assay: (Precipitation titration by using the modified Volhard’s method

Weigh accurately 0.2gm ammonium chloride in 40ml distilled water , 3m1 of nitrobenzene ,
nitric acid and 0.1N AgNO3 solution 30ml. Shake Vigorously for one minute and titrate with 0.1N
ammonium thiocyanate using ferric ammonium sulphate as the indicator.

Nitrobenzene is used for this assay 1s to avoid the interaction between the precipitated silver chloride
and ammonium thiocyanate.

NEC] + AgNO; ————> Agel} + NELNO;
AgNO; + NHsSCN ———— AgSCN + NH,sNO;
Silver nitrate Ammonium Silver
thiocyanate thiocyanate
NHgSCN + FeNHg4 (SO4), =» +~Fe(SCN)3 + 2(NH4)SOg

Ferric thiocyanate

(Red colour)

Uses:

° It is used as expectorant, Diuretic and systemic acidifier.

4.2 EMETICS

Emetic is derived from the word emesis which means vomiting. Vomiting may be defined as
forceful expansion of the contents present in the stomach through the mouth and sometimes
through nose.

“Emetics are the agents which when administered orally or by injection induce / evoke the
vomiting”

e Sometimes emetics are added in cough preparation in low dose to stimulate the flow of
respiratory tract secretion.

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e Emetics are also used as mechanical antidotes that are given before absorption of poison
into intestines or absorbed in blood. So, patient expel out the toxic substance.

e Most of the salts in higher doses act as emetics.

e Emetics should not be given in conditions like CNS depression, shocks, unconscious or
semiconscious conditions.

Mechanism of Action:
Emetics generally act by two ways:

(i) By stimulation of Chemoreceptor Trigger Zone (CTZ) located in the areas of postrema
medulla oblongata in brain

(ii) By refluxly producing irritation on g.it. tract. E.g: Copper sulphate, Sodium chloride,
Zinc Sulphate, Antimony potassium Tartarate

Commonly used emetics are salt water and mustard. Inorganic salt includes antimony potassium
tarrate, Zinc sulphate and copper sulphate. The common side effects of emetics are dehydration.
So the patient must be kept hydrated.

Copper Sulphate

Molecular Formula: CuSO4.5H20
Molecular Weight: 249.7 g

Synonyms: Blue Vitriol, Cupric sulphate
Method of Preparation:

The preparation of copper sulphate employs two step reactions. In the first step, copper
granules are heated with sulphur; a mixture of copper sulphate and cupric oxide (CuO) is
obtained. The resulting solution is then filtered to separate copper sulphate crystals.

In the second step, the residue i.e. CuO is again treated with dil.sulphuric acid to convert
it completely into copper sulphate.

302
3Cut+ S—~ CuSO4+ 2Cu0
Dil.H2SO4

2CuQ_ ———— —s_- 2Cu SO, + HO

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Properties:

e It exists in the form of deep blue crystals of pentahydrate available in the form of
granules or powder.

e It shows effervescence in dry air slowly
e It is soluble in water, very soluble in boiling water and insoluble in alcohol.
e Itis acidic in nature, changes blue litmus red.

e On heating at 100°C, it loses two molecules of water, at 140°C another molecule of water
and at 200°C, a white anhydrous salt is formed.

100°C 140°C
CuSO4.5H20 ———> CuSO4.3H20 + 2H20 = —— CuSO..2H20 + H20
200°C

CuSO, (Anhydrous salt)

Assay: (Oxidation — Reduction (Iodometry)

Principle:

The assay is done on the basis of the oxidation-reduction reaction of iodine/ sodium
thiosulphate. A solution of copper sulphate is first of all treated with potassium iodide and acetic
acid. Cuprous iodide (Cul) is formed and iodine is liberated. This liberated iodine is made to
titrate with 0.1 N sodium thiosulphate

In the reaction, cupric iodide (Culz) is first of all formed, but as it is unstable it gets
decomposed to cuprous iodide (white precipitate) and free iodine. The iodine is made to titrate
with sodium thiosulphate solution using mucilage of starch as an indicator. When the blue colour
is disappearing, potassium thiocyanate is added and the titration is continued. As the reaction
leading to the liberation of iodine is reversible (2Cul2 gq» Cuzl2 + I), it is completed by the
addition of potassium thiocyanate. Cuprous thiocyanate precipitate has been more sparingly
soluble in water than cuprous iodide. The titration with sodium thiosulphate is continued until
the blue colour disappears.

CuSO, + 2K. —————* Cul + K2SO4

cupric iodide

2Cuk ———_—- Cwh + In
cupric iodide cuprous iodide
(Unstable) (Stable)

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Decomposition of cupric iodide into cuprous iodide and iodine is reversible. Potassium
thiocyanate is added to check this reversible reaction by forming cuprous thiocyanate as follows:

Ch + 2KSCN ———> 2CuSCN + 2KI

Cuprous pot.thio- Cuprous
iodide cyanate thiocyanate

2Na2S203 + Ip ——————» NaoS406 + 2Nal

Sodium thio- Sodium tetra
sulphate thionate

Procedure:

An accurately weighed copper sulphate is first of all dissolved in water with the aid of a small
amount of dilute sulphuric acid and the volume is made up to 100ml mark in volumetric flask. A
solution equivalent to about 1g is put into the iodine flask and treated with an excess of
potassium iodide (3g), 5ml of acetic acid is added and the contents are shaken well. The liberated
iodine is made to titrated with 0.1 N sodium thiosulphate solution till the dark iodine colour in
the flask changes to yellow. At this stage Iml of starch mucilage solution (indicator) is added.
Blue colour is formed. The titration is continued to faint blue colour. Towards the end of titration
2g of potassium thiocyanate is added, the contents are titrated, and the titration is continued until
the blue colour gets disappeared.

Uses:

1. It is used as an emetic but in large doses, it is corrosive in nature.

2. Itis considered as a chemical antidote in phosphorus poisoning.

3. Externally, it is used as an astringent and fungicidal (1.5% solution).
4. Itis an ingredient of Benedicts and Fehling’s reagent.

5. Itis used in the detection of water and in the preparation of absolute alcohol.

Sodium Potassium Tartarate

Molecular Formula: C4HaKNaOo.4H20

Molecular Weight: 282.22 g

Synonyms: Rochelle salt, seignette salt

Method of Preparation:

It is prepared by the reaction of tartaric acid with sodium and potassium chloride with the

evolution of HCl

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i ‘

HO-e —COOH HO — —COOK

HO~E —COOH +NaCl +KCl ———* _ HO 4 —COONa + 2HCl
H H

Tartaric acid Sodium potassium tartarate

Properties:

1. It is white crystalline powder or available in prismatic crystal form.
2. It is odourless and have cooling saline taste.

3. It effervescence in dry air.

4. It is freely soluble in water and insoluble in alcohol.

5. When it is heated to 74°C, it gives inflammable vapours of burnt sugar with residue of
potassium and sodium carbonate.

CaHaKNaQOs + 502 —————» _K2CQ3 + 6CO2 + 4H20
Dose:
10gm (range 8 — 16gm). Children may be given half the adult dose.
Uses:
1. It is used as a saline cathartic.
2. Depending upon the dose, it is also used as mild laxative.
3. It can also be used as diuretic and urinary alkaliser.
4. It is used as food additive, as a stabilizer in meat and cheese products.

5. It is an ingredient of compound effervescent powder.

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4.3 HAEMATINICS

These are the agents which are required for the formation of blood cells and also used in
the treatment of anaemia. The main haematinics are iron, vitamin Bi2 and folate ions.
These agents increase the number of erythrocytes or haemoglobin content in the blood.

Eg.
Ferrous sulphate, ferrous gluconate, ferrous fumarate, ferrous ascorbate

Haematinics drugs are available in combination with folic acid + zinc + vitamin Bi2 in
tablet, capsule, syrup and suspension forms.

Anaemia is decreased capacity of RBCs to carry oxygen to the tissues. It occurs when the
balance between production and destruction of RBCs is disturbed. The disturbance can
occur due to:

a) Blood cells.

b) Impaired red blood cell formation (due to deficiency of essential factors i.e iron,
vitamin B12, folic acid or bone marrow depression).

c) Increased destruction of RBCs(haemolytic anaemia)

Tron Deficiency Anaemia:

Iron deficiency anaemia results from inadequate intake of iron in routine dict, by blood

loss, g.1.t tract infection or excessive loss of blood in female menstruation cycle etc.

The daily dietary requirement of iron is 1Omg in male and 18mg in females. The main

sources of iron are leafy vegetables, grains, cereals, meat, egg yolk etc.,

Ferrous Sulphate

Molecular Formula: FeSO1.7H20
Molecular Weight: 278 g

Synonyms: Green Vitriol, iron vitriol

Method of Preparation:

i.

i.

It is obtained by adding slight excess of iron to dilute sulphuric acid, iron gets dissolved
to form ferrous sulphate and hydrogen gas is evolved. The liquid is then concentrated and
cooled to get crystals.

Fe + H2SO, ————> FeSO, + Hp 4

On commercial basis, it is obtained by exploring moist iron pyrite (FeS2) to air, it gets
oxidised slowly and forms ferrous sulphate.

2FeS2 + 2H20 + 202 ———2F eSO.4 + 2H2SO4
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Properties:
e It occurs as odourless bluish-green crystals or powder.
e Its taste is metallic and astringent.
e It effloresces in dry air.
e Onexposure to moisture, it gets oxidised and becomes brown in colour.
e On heating, it decomposes to ferric oxide, sulphur dioxide and sulphur trioxide.
2FeSO4 —————> Fe203 + SO2 +SO3
e It reduces the salt of silver and gold to their corresponding metals.
Ag* + Fe?” » Ag+Fe**
Au*’ + 3Fe?* —______-» Au + 3Fe**

e It decolorizes acidified potassium permanganate and turns acidified potassium
dichromate green.

Assay: (Oxidation — Reduction (Permanganometry)
Principle:

The assay is carried out on the basis of the oxidation-reduction reaction. Ferrous salts can be
readily oxidised under ordinary conditions to ferric form. The ferrous sulphate can be titrated in
an acidic medium to ferric form by potassium permanganate until a faint pink colour appears.
Hydrochloric acid or nitric acid cannot be used for acidification of the sample.

2KMnO,4 + 8H2804 + 1OFeSO4 —————PK2804 + 2MnSOz + 5Fe2 (SOx)3 + 8H20
Procedure:

An accurately weighed amount of about 1g of a substance is first of all dissolved in 25-30 ml
of water. To it 20ml of dilute sulphuric acid is added and the solution is made to titrate with 0.1
N potassium permanganate solution until a faint pink colour is produced.

Uses:
1. Itis used as haematinic i.e, promote the formation of haemoglobin.
2. Itis used in the treatment of anaemia caused by iron deficiency.
3. Itis used to dye fabrics and in tanning clothes.

4. Itis used in the manufacturing of ink and in photography.

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5. Itis used as an insecticide in agriculture.

Ferrous Gluconate

Molecular Formula: Ci2H22FeO14.2H20
Molecular Weight: 482.18 g

Synonyms: Iron gluconate, Glucoferron

Method of Preparation:
i. It is prepared from ferrous carbonate(freshly prepared) which is heated with gluconic acid

in aqueous media

CH2OH. (CHOH):. COOH + FeCO3+H20 = —> Coo
(CHOH). | Fe2* + 2H2O + COz.*t
|

CH20H |2

ii. It can also be prepared by double decomposition reaction between calcium gluconate and
ferrous sulphate. Calcium sulphate insoluble and filtered off. The filtrate is concentrated
to get grey colour particles of ferrous gluconate.

coo coo
(CHOH). | Ca?* +FeSO, ————-» |(CHOH). | Fe + CuSO: }
| |

CH20H CH20H

Properties:

It is a fine yellowish grey or pale greenish yellow powder.

It has an odour like burnt sugar.

It is light sensitive as it is oxidised to ferrous ion in light.

Its aqueous solution is stabilizer by the addition of glucose.

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4.4 POISON AND ANTIDOTES

A poison may be defined as any substance administered in whatever in way (by mouth, injection,
inhalation, skin, mucous membrane) produces ill health, disease or death.

The diagnosis of poisoning is then difficult, but acute poisoning may be accidential,
occupational, suicidal or criminal.

Self- medication is also a major cause of drug poisoning.
Classification of Poisoning:
e Intentional Poisoning:

A person taking or giving a substance with intention of causing harm to that person. e.g
Suicide

e Unintentional poisoning

If the person taking or giving a substance without knowing its toxic effects. e.g
Accidentally.

e Undetermined:

When the distinction between intentional and unintentional is not clear e.g poisoning due
to insecticides or pesticides.

Signs and symptoms of Poisoning:
e Reduced breathing rats
e Nausea vomiting and diarrhoea
e Increased or decreased heart rate
e Dilated or shrunken pupils
e Muscle cramps

Heavy Metal Poisoning

Heavy metal poisoning occurs due to intake of salts of arsenic, lead, mercury, iron and
cadmium, depending upon the content and type of heavy metal, toxic effect can be seen in the
future.

Treatment:

Activated charcoal is given initially for absorbing heavy metal or poisons. Then the emetics
are given to eliminate any poison left in the stomach. Some inorganic compounds precipitate the

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heavy metals and prevent their absorption in blood circulation, e.g: Activated Charcoal, light
kaolin, copper sulphate, magnesium sulphate etc.

Cyanide poisoning

Cyanide poisoning may occur by inhalation of fumes of hydrocyanic acid (HCN), ingestion
of inorganic cyanide salt or cyanide releasing substances like cyanamide, cyanogens chloride,
peach of apricot, bitter almond, photographic chemical and silver polishes.

Consumption of 300mg of potassium cyanide may cause death.
Physiology of cyanide in body

Cyanide readily combines with ferric ion of cytochrome oxidase, which prevents the
electron transfer and stops the cellular respiration or oxidation-reduction reaction.

Treatment:

Sodium nitrite and sodium thiosulphate injections both the antidotes one by one are
administered for the treatment of cyanide poisoning.

ANTIDOTES

“* Antidotes may be defined as those substances which react specifically with an ingested
poison or toxic substance or an overdose of a potent drug.

“+ They act either by neutralizing the poison or its toxic effect or pharmaceutically
(antagonistic action) or chemically by converting them to non-toxic or less toxic forms (
eg. Chelates, acids, insoluble derivatives).

“* It is possible to classify antidotes on the basis of their mechanism of action as follows;

“)
Physiological antidotes Chemical antidotes Mechanical Antidotes
Eg. Eg. Eg.
Charcoal, D-Penicillamine, Sodium nitrite (NaNOz2),
Light kaolin. Desferrioxamine, Sodium thiosulphate (Na2S203).
Dimercaprol.

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“* For cyanide poisoning two inorganic antidotes such as sodium nitrite and sodium
thiosulphate are used. Both are used in conjuction with cach other.

Mechanism action of cyanide poisoning:

Cyanide poisoning cyanide ion
Combines with ferric ion
Cytochrome oxidase

Which binds cyanide ions
For electron transfer reaction

This causes stoppage
Of cellular respiration
And metabolic reaction

Haemoglobin
NaNO2

Methaemoglobin

Cyanide-Methaemoglobin
Complex

slowly gets dissociated
Na28203

Non-toxic thiocyanate

|

Excreted by the Kidney

+ Another compound dicobalt edetate is even more specific and directly reacts with cyanide
ions to yield a stable non-toxic ‘cobaltcyanoedetate complex’. Both dicobalt edetate and
sodium nitrite are toxic. Hence either procedure is recommended only when cyanide

poisoning is confirmed.

Sodium Thiosulphate

Molecular Formula: Na28203.5H20

Molecular Weight: 248.18 g
Synonyms: Sodium hyposulfite, Anti-chlor.

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Method of Preparation:

i. One half of a concentrated solution of sodium carbonate is saturated with sulphur dioxide
and the other half is add to, it sodium sulphite is formed.

NaxCO3 + 2SO2+H20 9 ———2NaHSO3 + CO2
2NaHCO3+ Na2CO3 ————Na2S0O3 + H20 + CO2

Sodium thiosulphate solution is prepared by boiling sodium sulphite solution with
flowers of sulphur and stirring till the alkaline reaction has disappeared.

NazSO3+ § > NaS8203

The excess of sulphur is filtered off and the filtrate evaporated to crystallization when
Crystals of sodium thiosulphate ( Na2S203.5H20 ) separate on slow cooling.

ii. It canalso be prepared by passing sulphur dioxide into sodium sulphide solution.
2Naz28S + 3802. ——— 2Nar8203 + S.
Assay: (Iodimetry Titration Method)
0.8g¢ of substance accurately weighed is made to dissolve in about 30ml of water in a
conical flask. This is titrated with 0.1N iodine solution added from a burette towards the end

point, 3ml of starch solution is added as indicator. The end point can be recognized, by the
yellow colour of iodine, which gets discharged by shaking for a few seconds.

2Na2S203 + Ib ————» NaoSu0¢ + 2Nal

Uses:
e It is used as an antidote for cyanide poisoning.
e Sodium thiosulphate is also a very important reducing agent and is used as a standard
titrant in iodimetric analysis.

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Activated Charcoal

A mixture of 50% of activated charcoal, 25% magnesium oxide, and 25% tannic acid is called as
“universal antidote”.

Preparation:
Commercially, it is obtained as a residue during destructive distillation of various organic

matters or from burning of organic materials in a special manner. The coarse material is crusted
and powdered.

Properties:

e Itisa fine black, odourless, tasteless powder having smooth touch and free from

gritty particles.
e It is almost insoluble in usual solvents. The fine powder provides more surface area
for adsorbent properties.

Action and uses:

“+ It is a general type of adsorbent which finds use in poisoning. If not only adsorb heavy
metals, but also adsorb drugs such as hypnotics, sedatives, alkaloids etc. and also gases
like carbon monoxide, CO2, NO etc.,

“* It is normally employed in the ratio of 5:1 or 10:1(Charcoal to poison).

“+ It is administered in the form of tablets.

%¢ It also finds use in diarhoea to adsorb toxins.

Sodium Nitrite

Molecular Formula: NaNO2
Molecular Weight: 69 g
Synonyms: Nitrous acid Sodium Salt, Etinitrit.

Method of Preparation:
This is manufactured by many methods. The most suitable method involves the passing
of nitrogen oxide gas (NO) obtained during the catalytic oxidation of ammonia and oxygen in

sodium carbonate solution. The solution is concentrated to crystallize out the product.

2NaxCO3 + 4NO +O. ————® 4NaNO+ 2COrf

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Properties:

Sodium nitrite occurs in the form of white granular powder or as a white crystal having a
saline taste.

It is water soluble, sparingly soluble in alcohol.

When exposed to air it deliquesces and gets slowly oxidized to sodium nitrate.

In medicine, it was used as a vasodilator but has been now largely replaced by organic
nitrites and nitrates, nitroglycerin and isosorbide dinitrate.
Medicinally, it is mainly used as antidote in cyanide and has a hypotensive effect.

In cyanide poisoning (sodium or potassium cyanide or hydrocyanic acid or bitter
almonds) a 3% w/v solution of sodium nitrite is slowly infused intravenously, until 10ml
(300mg) over a period of 3 minutes has been administered. Then this is fillowed by 25ml
of a 50% w/v solution of sodium thiosulphate ( 12.5 ) infused a period of 10 minutes

4.5 ASTRINGENTS

These are the compounds which bring about protein precipitation. They are usually
applied to damaged skin topically or to the mucous membrane of the GIT including the
mouth.

Mechanism action of Astringents:

Astringents are able to reduce the cell permeability due to their protein precipitation
action.

Transcapillary movement of plasma protein

| Astringents

Reduce local edema, exudation and inflammation

|

Decreased mucous secretion

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When applied topically, astringents in low concentration are found to stimulate growth of
a new tissue.

High concentration of astringents ————-» Corrosive effect on contact with tissue

The metal would form complex with various polar groups present on the protein or an
enzyme. This complexation of important functional groups at the active site of protein or
an enzyme causes a drastic change in the properties of the protein.

Eg.Alum, Zinc sulphate, Zinc chloride

Zinc Sulphate

Molecular Formula: ZnSO4.7H20
Molecular Weight: 287.54 g

Synonyms: White Vitriol.
Method of Preparation:

L

il.

It is obtained by heating zinc blende ( zinc sulphide) in the presence of air under specified
conditions. The heated mass is dissolved in hot water, filtered and the solution is
concentrated for crystallisation.

ZnS + 202 ————>_ Zn SO4

It is obtained by digesting metallic zinc granules in dil.H2SO4. The solution is filtered to
separate the undissolved metallic zinc and filtrate is trated with chlorine to oxidise any
ferrous sulphate impurity into ferric sulphate which is then precipitated by hydroxide and
removed. The filtrate is concentrated and left for crystallization.

Zn+H2SO0, ————> ZnSO:+H> #

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Properties:

Uses:

It forms colourless transparent crystalls, prisms or needles, or as a granular, crystalline
powder.

It is odour with an astringent and metallic tase. It is very soluble in water, glycerin but
insoluble in alcohol.

When it is strongly heated, it decomposes,

50°C 100°C 450°C
ZnSO4.7H20 ————> ZnSO4.2H20 —— ZnSO..H20 —— ZnSO,
v40’c|
ZnO

With ammonium and potassium sulphate , it yields double salts

Eg. ZnSOu. K2SO.4.6H20.

ZnSO4 + (NH4)2804 ———» ZnSO4.(NH4)2804.6H20
Zinc ammonium sulphate.

Zinc sulphate reacts with potassium ferrocyanide to form white precipitate of zinc
ferrocyanide. The precipitate remains insoluble in dil.HC1 solution.

2ZnSO4 + Ka(Fe(CN)s) ————» ZmFe(CN)6 + 2K2804

Zinc sulphate reacts with NaOH the white precipitate of Zn(OH)2 is formed.

ZnSO«4 + 2NaOH ———» Zn(OH)2 + 2NaCl.

Zinc sulphate acts as an emetic acting upon the vomiting reflex.
Externally , it is used in solutions and powders as astringent.
For ophthalmic purpose 0.25% solution is employed.

The aqueous solution of zinc sulphate is used for protein precipitation

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Potash Alum

Molecular Formula: KAI (SO,)2.12H20
Molecular Weight: 474.33 g

Synonyms: Potash Alum, Aluminium potassium Sulphate

Method of Preparation:

It is obtained by adding a concentrated solution of potassium sulphate to a hot solution of an
equimolecular proportion of aluminium sulphate. When the solution is concentrated and cooled,
characteristic octahedral crystals separate out.

K2804 + Abk(SOa)2 + 24H20 ————=s 2 KAI](SO,)2.12H20

If crystallization is done slowly, large characteristic regular octahedral crystals are obtained.

Properties:

Uses:

It is available as colourless, transparent or granular crystals having a sweet astringent
taste.
It is soluble in water but insoluble in alcohol

It uses externally for its astringents properties.

Barbers usually use alum by wetting it and rubbing it on skin after shave, perhaps for its
astringent and antiseptic action.

Alum is used as a Pharmaceutical aid.

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UNIT-V

Radioactivity:

The atoms of heavy element such as uranium and thorium unstable. In their nucleus the neutron
to proton ratio is high only nuclei which have same number of neutron and proton are stable. So
the nucleus of elements like uranium-235 throw (or ) emits some particles like alpha particle and
beta particle and also some radiation like the gamma rays in order to attain the stability. This is

known as radioactivity

UNIT OF RADIOACTIVITY

1.

CURIE

The unit of radioactivity is “curie’. Which is symbolised as ‘’C’’. It may be defined as
the quantity of any radioactive substance which undergoes the same number of

disintegrations in unit time.

1g of radium is equal to 3.7 X 101° disintegration/ second. Millicurie( me ) = 1 X 10°
curie = 3.7 X 107 disintegration/ second. Microcurie ( uc ) = 1X10° curie = 3.7 X 104

disintegration/ second

Roentgen ( R)
It is the unit of exposure

1R=2.58 X 107 C Kg! (C=acoulomb )

RAD
It is the unit of absorbed dose

1RAD= 107 JKg!
Eg
Air —0.87 RAD

Water-0.97 RAD

REM
It refers to the unit of dose equivalent.

Exposure rate constant
It refers to the does rate in roentgens/ hour at 1M distance from 1 Curie.

Pharmaceutical dosage forms may be described in terms of RAD units.

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APPLICATIONS OF RADIO ISOTOPES
Radio isotopes find use in medicine in four different ways.

Radiation source in therapy

Radioactive tracers for diagnostic purpose
Research

Sterilisation

FYeNr

1) Radiation source in therapy

In therapeutic use of radioisotopes, the radiations emitted cause destructive effects on
existing cells and disallow the formation of new cells and tissue, due to this reason,
the radio isotope therapy has been applicable to those disease conditions in which
extensive cellular metabolic malfunction exists.

Eg.

1.Gold( 198 aU) finds use in the treatment of abdominal and pleural effusions
associated with malignant tumors. It is given in the form of colloidal gold suspension.

198 AU also finds use in the treatment of carcinoma of uterus and urinary bladder.

2. Sodium phosphate ( 325) finds use in the therapy of polycythemia vera to decrease
the rate of formation of erythrocytes leukemia.

3. cobalt labeled cyanocobalamins( vit.b12 ) finds use in the diagnosis of pernicious
anaemia.

2) Radio isotopes in diagnosis

1. Labelled cyanocobalamin finds use for measuring the glomerular filtration rate.
li.Ferric citrate OFe) injection finds use for the diagnosis of haematological disorders.

lii.Colloidal gold (198

volte AU) injection has been used for diagnostically studying the blood circulation in
the liver.

131

tv. Sodium iodide (~~ “T) injection finds use for diagnose the functioning of thyroid gland.

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3) Research
Excellent biological and medicinal studies have been carried out with radioactive isotopes as

tracers.

Eg 6C!4 and H? are most commonly used radio nuclides for this purpose.

4) Sterilisation

Excellent use is being made of the radiation constantly available from some strong radiation
source for sterilizing pharmaceuticals in their final packed containers and surgical instruments in
hospital. The radiation does not destroy or harm most pharmacetricals.

Thermolabile substances such as vitamins, hormones, antibiotics etc. Can be safely sterilised.

Eg. 27COâ„¢ (or) Cesium-137 may be used for sterilizing surgical instruments.

HAZARDS AND PRECAUTIONS OF RADIOACTIVE MATERIALS

» In order to have protection from hazards of radiation. Radioactive materials must be
stored in an area not frequently visited by people. Shielding may be required thick glass
or Perspex container usually provides sufficient shielding. The storage area must be
regularly checked for the radioactivity.

If radioactive liquid has to be handled, it must be carried in trays having absorbent
tissue paper so that any spillage will get absorbed by paper. Rubber gloves have to be
used when working with radioactive liquids. Pipettes operated by mouth should never be
employed.

PRECAUTIONS

> One should not touch radioactive emitter with hand but it should be handled by means
of forceps ( or ) suitable instruments.

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Smoking, eating, and drinking activities should not be done in the laboratory where
the radioactive materials are handled.

Sufficient protective clothing ( or ) shielding have to be used while handling the
materials.

Radioactive materials have to be stored in suitable labelled containers, shielded by lead
bricks and preferably in a remote corner.

Areas where radioactive materials have been stored ( or ) used should be monitored that
is , tested for radioactivity regurarly.

Disposal of radioactive materials should be carried out with great care.

RADIO- PHARMACEUTICALS

e These are more or less like pharmaceutical preparations ( solutions, injections etc., )
with all the usual controls for such preparations. But these are prepared by scientists
at the Bhabha Atomic Research Centre (BARC) at Mumbai and supplied to approved
hospitals and approved laboratories. They all have a radioactive isotope.

e A tadioactive pharmaceutical preparation is named by one of these
methods. Eg.

Sodium radio-iodide injection ( or ) Sodium iodide-1!*! capsules.

e The IP does not includes any radioactive pharmaceutical preparation. B.P
includes-12 preparations, U.S.P includes -24 preparations.
Some important inorganic Radio Pharmaceuticals available from( BARC )

S.No Name of the product Radionuclide present Application

in it

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Ammonium bromide inj Br-82 Extra cellular water
measurement
Calcium chloride solution Ca-45 Study of calcium
metals disorders
Colloidal Gold inj AU-198 Treatment of
cancers and study
of RES
Cyanocobalamin CO-57 (OR ) CO-58 Diagnosis of
preparation pernicious anemia

Rubidium chloride inj Rb-86 Determination of
myocardial blood
flow

Sodium chloride inj Na-24 Study of sodium
exchange

Sodium iodide cap 1-131 Study of thyroid
uptake

Sodium ortho phosphate sol | P-32 Treatment of

polycythemia

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Sodium Iodide (I 131 ) Solution

Sodium iodide ( 3! ) solution is a solution which is suitable either for oral ( or )

131

intravenous administration, having radioactive. 1°~” which is processed in the form of

sodium iodide from the products of urantum fission ( or ) the neutron bombardment of
tellurium. Sodiumthiosulphate ( or ) other suitable reducing agent is also present.

Description:

It is a clear, colourless solution. It has a half-life of 8.06 days and emits beta
particles and gamma rays.

Test for Identity:

The gamma ray spectrum of this solution is compared with the gamma ray
spectrum of a standardized iodine-131 solution. There should be no significant
difference. Further the principle gamma proton has an energy of 0.36MeV.

PH:
75-90
Radiochemical Purity:

This test is meant to ensure that all the radioactivity is present only in the iodide
ion and not because of the presence of some other iodine containing compound
such as the iodate.

It is done by paper chromatography in this it should be proved that the
radioactive part of the paper chromatogram coincides with the position of the iodide

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ion. It should also be proved that the position corresponding to the iodate ion has no
radioactivity.
Assay:

By using a suitable counter, the activity is compared with the activity of a
standardized iodine-131 solution. It should have the iodine-131 activity and specific
activity ac prescribed.

Use:
Used for the diagnosis and treatment of disorders of the thyroid gland.

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Subject:
Pharmaceutical inorganic chemistry
Semester:
First Semester
Cource:
B.Pharm

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