PHARMACEUTICAL INORGANIC CHEMISTRY

Chapter 3

GASTRO INTESTINAL AGENTS

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 GASTROINTESTINAL AGENTS
INTRODUCTION:

The gastrointestinal (GI) system is made up of the GI tract plus accessory organs. In essence,
the GI tract is a long hollow tube that extends from your oral cavity where food enters your
body, via the esophagus, stomach, small intestine, large intestine, rectum, and finally to the
anus where undigested food is expelled. The accessory organs include the salivary glands,
pancreas and liver. These secrete important enzymes into the digestive tract. The gall bladder,
which stores bile is also considered a part of GI system

The function of the GI system is to process nutrients and energy from food and fluids that you
ingest. To do this, the GI system first needs to break foods down or 'digest' them into their
simplest forms. The main components of food are carbohydrates, fats, proteins, vitamins,
minerals and fibre. Food also contains varying amounts of water. The process of digestion
breaks starch and sugars from carbohydrate-rich foods such as bread, potatoes and pasta into
simple sugars such as glucose and fructose. Fats in butter, cheese, meat etc are converted into
cholesterol and fatty acids. Proteins, for example in meat, eggs and fish, are broken down into
aminoacids.

When you eat and drink, digestion begins when you chew food to break it down into smaller
pieces and enzymes within your saliva (excreted from salivary glands) begin to break the
foods down into the component parts. Swallowed food and fluids travel down your throat into
your esophagus and then into your stomach. Once within the stomach, the food and fluids are
mixed with strong acids that dissolve the solids, and digestive enzymes continue to break the
food down. Next, the mixture passes into the small intestine where it is digested further by
juices from your pancreas, liver (which produces bile) and small intestine. The nutrients are
then in an accessible form and can travel through the wall of the intestine into the
bloodstream (a process known as absorption) to be delivered to cells throughout your body.
Undigested food in the small intestine moves into the large intestine (where some of the water
is reabsorbed into the body) and is then expelled from the body as faeces or 'stools'.

When ever the above function goes wrong, there occurs a disease or undesirable conditions.
Some of these are as follows:

 Whenever inadequate secretion of acid takes place in the stomach, this causes
achlorhydria or hypochlorhydria.
 Whenever an excess secretion of acid takes place in the stomach, this causes the
imbalance of the acid enzyme ratio, thereby leading to hyperacidity and ulcers.
 There may occur accumulation of toxic substances or gases
 There may occur inadequate absorption of fluids and minerals from large intestine,
thereby causing diarrhea.
 There may occur insufficient peristaltic movement of large intestine thereby causing
constipation.

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  There may occur insufficient secretion of saliva, thereby making the food swallow
with difficulty
 There may occur ingestion of poisonous substances accidentally or intentionally by
some persons.

In people with GI problems, these functions are impaired. Digestion of foods can be reduced,
so fewer nutrients are converted into a usable form. Alternatively, food may be digested
correctly but nutrients may not be absorbed into the bloodstream for use by the body. Finally,
food and nutrients may be expelled too soon or specific nutrients and fluids may be lost via
the faeces

Pharmaceutical Inorganic agents used to treat gastro instential agents disorders include:

 Products for altering gastric P H

 Protectives for intestinal inflammation.
 Adsorbents for intestinal toxins.
 Cathartic or laxative for constipation.

Based on the above disorders, GIT agents can be classified mainly as

1. Acidifying agents
2. Antacids
3. Protective and absorbents
4. Saline Cathartic

ACIDIFYING AGENTS/ACIDIFIERS
Introduction: What is the role of hydrochloric acid in human body?

Hydrochloric acid is naturally produced by the cells of the stomach. It serves two main
functions in the stomach which are: to provide an optimum pH for the enzyme protease to
work and also to kill pathogenic organisms in the stomach. When the secretion of
hydrochloric acid in the stomach is reduced, the person suffers from a disease known as
hypoacidity or achlorhydria

Definition: Acidifiers are inorganic chemicals that either produce or become acid. These
chemicals increase the level of gastric acid in the stomach when ingested, thus decreasing the
stomach pH.

These are many types of acidifiers but the main four types are:

• Gastric acidifiers, used in controlling pH in stomach.

• Urinary acidifiers, used in controlling pH in urine.

• Systemic acidifiers, used in controlling pH in all the parts of body.

• Acid, mostly used in laboratory experiments.

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Gastric acidifiers, used in controlling pH in stomach:

In patients suffering from achlorhydria, there is deficient secretion of Hydrochloric acid in

stomach. In such cases gastric acidifiers are useful in providing the necessary acidity for the
proper digestion of food.

Cause of hypoacidity/achlorhydria:

Hypoacidity pertains to a condition of the decrease of acid in the stomach induced by lowered
hydrochloric acid secretion. This condition may happen secondary to other disorders such as
stomach cancer, pernicious anemia and infection with Helicobacter pylori or the treatment
with acid-suppressing medicaments or surgeries. Inorganic agents used in treatment
achlorhydria is dilute hydrochloric acid

Urinary acidifiers used in controlling pH in urine:

These are the agents which are used to render acidic urine to enable treatment of some types
of urinary tract disorders. Inorganic agents used as urinary acidifiers are ammonium chloride,
Sodium citrate

Systemic acidifiers are those agents which, when given usually by injection, act by reducing
the alkali reserve in the body and also useful in reducing metabolic alkaloids. The inorganic
agents used as systemic acidifiers are…………….

Acid, mostly used in laboratory experiments:

These are the agents used as pharmaceutical aids in the formulation, laboratory quality
control
…etc, Examples, concentrated and dilute mineral acids like Hydrochloric acid, Sulphuric
acid, Nitric acid

HYDROCHLORIC ACID

Hydrogen chloride is a gas; its solutions in water are commonly referred to as hydrochloric
acid.
Synonyms: Anhydrous hydrochloric acid; chlorohydric acid; hydrochloric acid gas;hydrogen
chloride; muriatic acid

Chemical formula: HCl

Molecular weight: 36.47 g/mol.

Standards: Hydrochloric Acid contains not less than 35.0 per cent w/w and not more than
38.0 percent w/w of hydrochloric acid

Method of preparation: 1) Hydrogen Chloride may be prepared in the laboratory by heating

Concentrated Sulphuric acid, with Sodium Chloride.

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 Calculated quantities of concentrated sulphuric acid and sodium chloride are heated in a cast
iron pan of salt cake furnace. The hydrochloric acid gas is formed which is passed in a tower,
which is sprayed with water. The dilute hydrochloric acid is collected at the bottom of the
pans. It is again circulated to the tower to absorb more hydrochloride so that it gets
concentrated. The acid so produced is then purified. Sodium busulphite formed in the process
is mixed with some more quantity of sodium chloride and heated strongly in amuffle furnance
to get more hydrogen chloride gas,

Chemical Reactions:
NaCl + H2SO4 ==> NaHSO4 + HCl

NaHSO4 + NaCl ==> Na2SO4 + HCl Overall

reaction is

2NaCl + H2SO4 ==> Na2SO4 + 2HCl

2) Industrially: It is prepared industrially by the combustion of Hydrogen, H2, in Chlorine,

Cl2.
Large amount of hydrogen and chlorine gases are obtained as by products by electrolysis of
sodium chloride solution during the manufacture of caustic soda( Sodium hydroxide). These
gases are dried and then combined to produce hydrogen chloride gas. The gas is cooled and
water is spread over the gas. The solution of hydrochloric acid flows to the storage tank.

Chemical Reactions:
H2 + Cl2 ==> 2HCl

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Storage: Store in stoppered containers of glass or any other inert material at a temperature
not exceeding 30°C

Medicinal uses: In dilute form used in the treatment of achlorhydria, given intravenously in
the management of metabolic alkalosis.
Other uses: Used as a pharmaceutical aid and laboratory reagent.

Dilute Hydrochloric acid

It contains 10 percent w/w of hydrochloric acid as Indian pharmacopeia

Standard: Dilute Hydrochloric Acid contains not less than 9.5 per cent and not more than
10.5 per cent w/w of hydrochloric acid

Ingredients:

Hydrochloric acid…………………… 274 g

Purified water……………………..726 g

Preparation: Specified quantity of hydrochloric acid is gradually added with stirring into
specified quantity of water taking in a specified volume of beaker. Mixed well and Store in
stoppered containers of glass or any other inert material at a temperature not exceeding 30°

Description: A clear, colorless liquid

Storage: Store in stoppered containers of glass or any other inert material at a temperature
not exceeding 30°C
Medicinal uses: In dilute form used in the treatment of achlorhydria, given intravenously in
the management of metabolic alkalosis.

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Other uses: Used as a pharmaceutical aid and laboratory reagent.

Ammonium Chloride:

Chemical formula: NH4Cl

Molecular weight: 53.5 g/mol

Standard: Ammonium Chloride contains not less than 99.0 per cent and not more than 100.5
per cent of NH4Cl, calculated on the dried Basis

Antacids
Introduction:

Antacids reduce acidity by neutralizing (counteracting) acid, reducing the acidity in the
stomach, and reducing the amount of acid that is refluxed into the esophagus or emptied into
the duodenum. Antacids also work by inhibiting the activity of pepsin, a digestive enzyme
produced in the stomach that is active only in an acid environment and, like acid, is believed
to be injurious to the lining of the stomach, duodenum, and esophagus.

Definition: Antacids are mild alkaline substances which reduce excess gastric acidity,
resulting in an increase in PH of the stomach and duodenum.

An ideal antacid should not have any side effects other than its main action of neutralizing
gastric acid.
An ideal antacid should satisfy the following criteria:

 The antacid should be insoluble in water and has fine particle form
 The ant acid should buffer in the PH range of 4-6
 The reaction of the antacid should not cause a large evolution of gas.
 The antacid should probably inhibit pepsin  It should not have a constipating or
Laxative effect.
 It should not cause, if absorbed, systemic alkalosis (in this condition the pH of the
body fluids and tissues is high).
 A prolonged and effective neutralizing action following an acceptable dose
 It should not cause precipitation of phosphate I the gastrointestinal tract and depletion
of phosphorus in the body.
 It should not also interfere with the absorption of food particles or other drugs such as
tetracycline from the gut.
 It should not also delay the absorption of drugs which are weak acids or speed up the
absorption of basic drugs. This happens when the pH of the gastric contents is raised.
 It should be palatable and inexpensive

In the case of antacids, the acid neutralizing capacity is important. The neutralizing capacity
of an antacid substance is expressed in milli equivalents of hydrochloric acid. Every antacid

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should have a neutralizing capacity of 5 mEq of hydrochloric acid per dosage unit. This is
enough to raise the PH in an essential empty stomach to 3.5.

Classification of antacids:
Antacids which locally neutralize the hyperacidity are broadly grouped into:
1) Systemic (absorbable) antacids: These are soluble, systemically can be readily
absorbable.
Systemic antacids can cause metabolic alkalosis after absorbing of their cationic moiety
(positively charged ion molecules) with long, excessive dosage For examples:
Sodium bicarbonate, which is soluble, readily absorbable and capable of producing systemic
electrolytic alterations and alkalosis and even absorption of Na + ions, is not suitable for
patient with hypertension, heart problem, liver failure or pregnant woman.

Calcium carbonate is also a potent antacid. However, with this drug, systemic absorption of
calcium can occur. Sometimes hypercalcaemia plus the systemic alkalosis caused by calcium
can also results in the milk-alkali syndrome.

2) Non systemic (non-absorbable) antacids: They are insoluble and poorly absorbed
systemically. Thus they do not exert any appreciable systemic effect. Non systemic
antacids are physically, physiochemically, chemically acting. Their cationic moiety forms
unabsorbable, insoluble basic compounds in the intestine. This group is further classified
based on the compounds used as antacids:
a) Aluminum containing antacids: Examples: aluminum hydroxide gel,
aluminum phosphate.
b) Magnesium containing antacids: Examples are heavy and light magnesium
carbonate, milk of magnesia, heavy magnesium oxide, magnesium tri silicate.
c) Calcium containing antacids: Examples are calcium carbonate, tri basic
calcium phosphate.

Rationale behind the combination therapy of antacids

Aluminium hydroxide:

• It is usually classified as non-systemic antacid.

• It does not interfere with electrolyte balance and not completely suppress the peptic
digestion.
• However, the formation of aluminium chloride result of reaction between aluminium
hydroxide and hydrochloride acid responsible for the astringent and constipation
effect.
• Besides, it interferes with absorption of phosphate.It reacts in the small bowel with
phosphate to form insoluble salts and is thus absorbed only to a very limited extent.

Magnesium hydroxide:

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 • Magnesium hydroxide is also a type of non- systemic antacid that interferes with the
absorption of folic acid and iron.
• It may induce diarrhea that causing loss of potassium ion in our body.

Sodium bicarbonate;

• It has a long history of use but has become less popular because of its tendency to
cause systemic effects.
• It is absorbed from the gastrointestinal tract and a slight alkalosis develops, with the
production of alkaline urine.

Calcium carbonate is also a potent antacid.

• Systemic absorption of calcium can occur

• Sometimes hypercalcaemia plus the systemic alkalosis caused by calcium can also
results in the milk-alkali syndrome.
• Like most other antacids it increases the gastric acid output when ingested a meal.

Some antacid may combine with simethicone (Decrease surface tension, thereby reduce
bubble formation - Added to prevent reflux); it is useful to prevent flatulence result from the
production of carbon dioxide gas.

Every single compound among antacid have some side effect especially when used for longer
period or used in elderly patients. On this basis the following combinations are in regular
clinical use.

To avoid certain side effects associated with antacids, combinations of antacids are used
such as.
1. Magnesium and aluminium hydroxides (Magaldrate)
2. Magensium and aluminium hydroxides, dimethicone (Dioval Forte Tabs)
3. Magnesium and aluminium hydroxides,methylpolysiloxane (Gelusil MPS)
4. Aluminium hydroxide gel, magnesium trisilicate (Gelusil)
5. Aluminium hydroxide gel, Magnesium hydroxide, magnesium trisilicate (Gelusil M)
6. Mag.hydroxide, dried alu, hydroxide gel, methylpolysiloxane, sod. carboxymethyl
cellulose (Digene gel).

Side effects of long term antacid therapy:

a) If pH raises too high rebound acidity to neutralize the alkali occurs.
b) Antacids which absorbed systemically exert alkaline effect on body’s buffer system.
c) Some antacids cause constipation while others have laxative effect.
d) Sodium containing antacids are problem for patients on sodium restricted diet.
e) Absorb drugs and form insoluble complexes so that are they not absorbed.

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Mechanism of action of antacids:
Compound Chemical Chemical Reaction
Formula

Aluminium hydroxide Al(OH)3 Al(OH)3(s) + 3 HCl(aq) -----> AlCl3(aq) + 3 H2O(l)

Calcium carbonate CaCO3 CaCO3(s) + 2 HCl(aq) -----> CaCl2(aq) + H2O(l) +

CO2(g)

Magnesium carbonate MgCO3 MgCO3(s) + 2 HCl(aq) -----> MgCl2(aq) + H2O(l) +

CO2(g)

Magnesium hydroxide Mg(OH)2 Mg(OH)2(s) + 2 HCl(aq) -----> MgCl2(aq) + 2 H2O(l)

Sodium bicarbonate NaHCO3 NaHCO3(aq) + HCl(aq) -----> NaCl(aq) + H2O(l) +

CO2(g)

Aluminium Hydroxide Gel

Synonyms: Aluminium Hydroxide Suspension; Aluminium Hydroxide Mixture

Molecular formula: Al (OH)3

Molecular mass: 78.00 g/mol

Chemical structure:

Standards: Aluminium Hydroxide Gel contains not less than 3.5 per cent and not more than
4.4 per cent w/w of Al2O3.

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Aluminium Hydroxide Gel is an aqueous suspension of hydrated aluminium oxide together
with varying quantities of basic aluminium carbonate and bicarbonate. It may contain
Glycerin, Sorbitol, Sucrose or Saccharin as sweetening agents and Peppermint Oil or other
suitable flavours. It may also contain suitable antimicrobial agents.

Description: A white, viscous suspension, translucent in thin layers; small amounts of clear
liquid may separate on standing.

Method of Preparation: For preparing this a hot solution of potash alum is added slowly to
a hot solution of sodium carbonate and not vice versa. The precipitate of aluminum hydroxide
is washed thoroughly with hot water till it is free from sulphate. The gel is then adjusted to
the required volume with distilled water.

Chemical Reaction:
3NaCO3 + 2KAl (SO4)2+ 3H2O → 3NaSO4+ K2SO4+2Al(OH)3 +3CO2

Precaution: If sodium carbonate solution is added to potash alum solution, then it is difficult
to wash out the sulphate completely. Due to adsorption by aluminum hydroxide, some
carbonate may be present.

In washing the precipitate of aluminum hydroxide hot water not boiling water should be used
as latter it may tend to decompose the aluminum hydroxide. It is to be remembered that a
hydroxide is formed instead of aluminum carbonate. The reason is that aluminum carbonate is
highly unstable it decomposes to give aluminum hydroxide and carbon di oxide

Storage: Store at a temperature not exceeding 30°C. Do not freeze.

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Medicinal Uses: Aluminium hydroxide is used as antacid in the management of peptic ulcer,
gastritis, gastric hyperacidity. It is also used as skin protectant and mild astringent.

Milk of magnesia: Magnesium Hydroxide Oral Suspension

Synonym: Magnesium Hydroxide Mixture, Milk of Magnesia; Cream of Magnesia,

Magnesium Hydroxide Oral Suspension is an aqueous suspension of hydrated magnesium
oxide.

It may be prepared from a suitable grade of Light Magnesium Oxide.

Standards: Magnesium Hydroxide Oral Suspension contains not less than 7.0 per cent and
not more than 8.5 per cent w/w of hydrated magnesium oxide, calculated as Mg(OH)2.

Description: A white, uniform suspension, which does not separate readily on standing

Method of Preparations: There are two methods of preparations (a) Hydration method and

(b) Hydration and Precipitation method.

(a) Hydration method:

Light magnesium oxide is hydrated with water to produce magnesium hydroxide.

Chemical Reactions:
MgO + H2O → Mg(OH)2.

This method is followed by industries and in Milk of Magnesia USP.

Draw backs of this method:

• This method produces highly viscous preparation that is difficult to pour out.
• The pH of the preparation is 10. This produces an alkaline taste that is unpleasant. So
0.1% citric acid is added to reduce the alkalinity and improve the taste.

Advantage: Industrially this method is used because this method does not require precipitate
washing

(b) Hydration and Precipitation method:

It involves four Steps:

Step I: A calculated solution of sodium hydroxide is triturated with calculated amount light
magnesium oxide to form a smooth cream. It is diluted with water.

Step II: The so formed cream is mixed with calculated magnesium sulfate solution with
stirring.

Chemical Reactions:
MgSO4 + 2NaOH → Mg(OH)2+ Na2CO3.

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MgO + H2O →Mg(OH)2

Step III: After some time the magnesium hydroxide will settle. The supernatant liquid is
decanted and the precipitation is washed with purified water. Again the supernatant liquid is
decanted. This process is continued until the preparation is free from sulfate.

Step IV: The precipitation is mixed with chloroform water to give the final preparation. Step

V. Finally the required strength of milk of magnesia suspension is prepared as per I.P

Advantages:

• The product is neither very viscous nor sediment quickly.

• Produce a salty taste that is more pleasant than the product obtained from hydration
method alone.
Medicinal uses of milk of magnesia use: As laxative, mild antacids, antiperspirant, dandruff
cure, redness reliever, oil absorber and acne buster

Storage: Store protected from moisture. Do not keep in a refrigerator.

Sodium Bicarbonate

Synonym: Baking soda

Chemical Formula: NaHCO3

Molecular weight: 84.01g/mol

Standards: I.P. limit: It contains not less than 99% and not more than 101% of NaHCO3

Description: A white, crystalline powder or small, opaque, monoclinic crystals. It gradually

forms sodium carbonate on heating in the dry state or in solution.

Method of Preparation:

1. By passing strong brine containing high concentrations of ammonia through a carbonating

tower where it is saturated with carbon dioxide under pressure. The ammonia and carbon
dioxide reacts to form ammonia bicarbonate which is allowed to react with NaCl to
precipitate NaHCO3 which is separated by filtration.

Chemical reaction

NH3 + H2O + CO2 → NH4HCO3

NH4HCO3 + NaCl → NaHCO3

2. It can also be prepared by covering sodium carbonate crystals with water and passing
carbon dioxide to saturation.

Na2CO3 + H2O + CO2 → NaHCO3

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Assay: Principle: acid base acidimetric titration

It is based on direct acid base acidimetric titration. Sodium bicarbonate being basic in nature
is estimated by titrating against standard acid like hydrochloric acid or sulphuric acid, where
neutralization between acid and base takes and end point is determined by using methyl
orange as indicator until the colour changes from yellow to red.

Note: in this titration we cannot use phenolphthalein as indicator because of formation of

carbonic acid towards end point.

Chemical reaction:

NaHCO3 + H2SO4 / HCl → Na2SO4/ NaCl + CO2 + H2O

Medicinal Uses: It is used as systemic antacid, and in electrolyte replacement.

PROTECTIVE AND ABSORBENTS

This group of GIT agents is commonly used for the treatment of mild diarrhea and dysentery
or other disturbances of GIT tract because of their ability to adsorb gases, toxins and bacteria.

Diarrhea is a symptom but not a disease. It mainly occurs because of improper digestion or
absorption of food or by bacterial infection. Diarrhea may be acute or chronic. Diarrhea is a
serious condition, particularly for very young or elderly patients, because there will be loss of
fluids and electrolytes can lead to dehydration and electrolyte imbalances.

Many chemical agents are used to treat diarrhea. Their main action is of protective and
adsorbent in nature. Chemically they are inert and insoluble salts and they form a protective
layer or coat on the mucosal membrane and provide a mechanical protection.

Furthermore, they adsorb the toxin, which are able to stimulate flow of electrolytes into
intestine causing watery stool. They may or may not have antibacterial action, in case of
serious cases they are advised to take antibacterial or antispasmodic drugs. The inorganic
compounds used as protective and adsorbent are bismuth salts, special clays like light kaolin
and activated charcoal.

Properties of protective and adsorbents;

• Chemically inert substances

• Used in treatment of mild diarrhoea and dysentery

• Ability to absorb gases ,toxins and bacteria

• Form a protective layer on painful ulcers in GIT

Light Kaolin

Synonym: Hydrated aluminum silicate.

Chemical formula: Al2O3.2SiO2.2H2O.

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Method of Preparation:It is prepared from natural clay It

involves the following steps:

• Powdering

• Particles separation by means of electrical sedimentation

• Purification from gritty particles and other impurities by elutriation

• Drying

• Storing in suitable container

How does it work?

Kaolin acts as a protective coating for the mouth to decrease pain associated with
radiationinduced damage.

Storage: Store protected from moisture.

Medicinal uses:

• Diarrhea, dysentery, colitis and cholera

• Adsorbent in food and alkaloidal poisoning
• Poultice
• Dusting Powders and filter aids

Bentonite: Al2O3.4SiO2.H2O.

Synonym: Wilkinite

Description: Pale buff or yellowish brown odorless, with slight earthy taste, Occurs as fine
powder practically insoluble in water and all inorganic solvents.

Medicinal uses: Used as suspending, emulsifying and stabilizing agent, excellent emulsifier
for o/w emulsions Used as a base for pharmaceutical preparations such as ointments, plasters
etc. It is also used as an adsorbent

Storage: It should be stored in airtight container in a cool and dry place.

SALINE CATHARTICS

Cathartics are drugs used to relieve constipation. The term laxative is used for mild cathartics
whereas purgatives is used for strong cathartics. They are also given for the expulsion of
intestinal parasite and also for clearing the bowels before surgery if necessary.

Constipation can be because of following reasons like weakness of intestinal, intestinal

spasm, emotional tension improper diet, lack of physical exercise or work, side effect of the

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drugs etc. In constipation fecal material becomes hard and dry, use of laxative and purgative
provides relief from constipation by elimination of bowel contents.

Cathartics or laxatives can be considered under the following class:

1. Mild laxatives: are those drugs, which promote evacuation of bowel with minimum
adverse effects. Drugs included in this group are:

• Bulk producing drugs: Which promote evacuation of bowel by increasing the stools
bulk volume and water contents. Eg; Isapgol, agar- agar methyl cellulose etc.
• Stool softeners (Emollient): Which penetrate and soften the stool. Eg: D-soctyl
sodium sulphosuccinate, liquid paraffin, etc.
2. Strong purgatives: Cause complete evacuation of the bowel and bowel become in
active and also given to remove the solid particles from intestine before certain x-ray
examination or surgery. There are two kinds of strong purgatives.

• Irritant or stimulant: These are drugs or chemicals, which act by local irritation or
intestinal tract and bring about stimulation of peristaltic activity. Eg Phenolphthalein,
senna, etc.
• Saline cathartics: These act by increasing the osmotic load of intestine by absorbing
large quantity of water and they’re by stimulating peristalsis.Eg: magnesium
compounds.

Magnesium sulphate

Synonym: Epsom Salt

Chemical formula: MgSO4 .7H 2O

Method of Preparation:

Laboratory: In laboratory it is prepared by treating a solution of magnesium carbonate with

dilute sulphuric acid. The mixture is stirred well and carbon di oxide is removed, then the
solution is evaporated to get the crystals of magnesium sulphate.

Chemical reactions:

MgCO3 + H2SO4→MgSO4+ CO2+ H2O

Commercially: Dolomite

It is prepared by reacting Sulphuric acid with dolomite. Dolomite is a mixture of magnesium

and calcium carbonate. The magnesium sulphate being water soluble remains in the solution
while the impurities such as calcium carbonate undergo precipitation, thus the solution id
filtrated and filtrate is subjected to evaporation to get the crystals of magnesium sulphate.

Chemical reactions:

MgCO3.CaCO3 + 2 H2SO4 →MgSO4 + CaSO4+ 2CO2+2 H2O

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Description: Colourless crystals or a white, crystalline powder with bitter and saline in tatse,
soluble in boiling water and practically in soluble in alcohol

Storage: Store protected from moisture Medicinal

uses:

• Saline cathartic as osmotic laxative

• Electrolyte replacement

Sodium Ortho Phosphate

Synonyms: Disodium Hydrogen Phosphate,Sodium ortho phosphate

Chemical formula: Na2HPO4 nH2O (n=12, 10, 8, 7, 5, 2 or 0)

Description: Colourless, transparent crystals; very efflorescent, Soluble in water and

practically in soluble in alcohol

Method of preparation: It is prepared by treating sodium carbonate with a hot solution of

phosphoric acid. The solution is neutralised, concentrated and crystals are separated,
centrifuged, washed and dried

Chemical reactions:

H3PO4 + Na2CO3→ Na2HPO4 + H2O+ CO2

Storage: Store protected from moisture

Medicinal uses:

• Saline cathartic
• Electrolyte replacement
• Standard buffer solution
• Softening hard water

Antimicrobial and astringent agents

Antimicrobial agents: These are the chemicals or its preparation that help in reducing or
preventing infection due to microbes. There are several terms used in describing anti-
microbial activity. First let’s study the definition of these terms.

Antiseptic: These are the agents or substances that are able to kill or prevent the growth of
microorganisms that is fungi, bacteria, etc. They widely applied on the living tissues. They
act by inhibiting the growth of microbial multiplication and metabolic activities or by killing
the microorganisms. An ideal antiseptic kills the microorganism without causing any damage

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to the host. They can be applied to all parts of the body and used in the form of mouthwashes,
soaps, deodorants, nasal spray, etc.

Disinfectants: These are the agents or substance that prevents infection by the destruction of
pathogenic microorganisms. They are usually applied to the non-living things like for the
sterlisation of surgical equipment. It is helpful in maintaining the public places like sanitation
or even in hospital etc. Some chemical disinfectants are too irritant and corrosive to the skin
or tissue, so it not used on the living tissue.
Germicide: These are substances that kill the microbes. This is further used more specifically
for different types of microbes like, bactericide for bacteria, fungicide for fungus, virucide for
virus, etc.

Those agents which do not kill the microbes but just inhibit the growth of microorganisms are
described by terms using the suffix stat for examples like bacteriostat, fungistat, etc., as the
Greek word static's means 'standing still'.

The term's antiseptic and germicide may be further specified according to their area and type
of use as topically or internally. Internal agents are those absorbed systemic and that not
absorbed internally that is nonsystematic.

An antimicrobial agent should have the following properties.

1. It should posse antiseptic or germicide activity and not bacteriostatic activity.

2. It should have rapid onset of action and sustained activity.

3. It should show good activity whatever might be the concentration of agent used.

4. It should not cause local cellular damage or should not interfere with body defenses.

5. It should not show any systemic toxicity from topical application.

6. It should have broad spectrum of activity against bacteria, fungi, protozoa, etc.

7. The topical antimicrobial agent should have favorable lipid water distribution coefficient
so that its effectiveness has been best.

Mechanism of action:

The Mechanism of action of these agents may range from mild astringent to powerful
oxidative processes. Inorganic compounds are generally not used internally but for topical
application like oral, skin infection, etc.

Inorganic compounds generally exhibit antimicrobial action by involving either of the

following three mechanism through,

1. Oxidation. 2. Halogenation. 3. Protein binding or precipitation.

These represent the primary chemical interactions or reactions that occur between microbial
protein and agent and result in death or inhibition of growth of microbes.

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Oxidation mechanism: Compounds acting by this mechanism belong to class of peroxide
peroxyacids, oxygen liberating compounds like permanganate and certain oxo halogen
anions. These anti-infective agents bring about oxidation of active functional groups present
in proteins or enzymes, which are necessary for the growth, or survival of microorganisms
and also which reducing in nature. These cause a change in the shape of the protein and there
by alter its function.
For examples: A free sulfhydryl group has been essential for function of various proteins and
enzymes. If this free sulfhydryl group is destroyed by oxidation into formation of di sulfide
group, the microorganism will die because of the altered protein molecule.

Halogenation mechanism: Compounds that are able to liberate the chlorine or hypochlorite
or iodine act by this mechanism. The category of agents act on the peptide linkage and alter
its potential and property. The destruction of specific function of protein causes death of
microorganisms.

Most of the enzymes are proteineous in nature. A protein molecule is composed of a variety
of amino acids connected through a peptide linkage (-CONH-) if an hypo chlorites attaches
the peptide linkage by replacing the H by Cl then protein molecule will have an altered
structure and the microorganisms.

Amino acid-CONH- Amino acid halogenation Amino acid -COCl-Amino acid.

(Protein structure) (Altered structure)

Protein precipitation: This type of mechanism involves the interaction of protein with
metallic ions having large charge or radius ratio or strong electrostatic fields. Hence most of
the metals belonging to groups IB, IIB, IIIA or transition metals show protective activity but
alkali alkaline earth metals do not show this activity. The nature of interaction of metal with
protein takes place through polar group of protein, which acts as ligand and metal ions as
Lewis acid. The chelate formed may be strong chelate giving rise to inactivation of protein.
This action in general non-specific and at sufficient concentration will react with host as well

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as with microbial protein. The protein precipitant properties of metal cations can be altered
accordingly to the concentration at the site of action.

By increasing the concentration, antimicrobial, astringent, irritant and corrosive properties are
available.

The various inorganic compounds studied under above mechanism are as follows:
Potassium permanganate, Boric acid, Hydrogen peroxide*, Chlorinated lime*, Iodine and its
preparations

Hydrogen peroxide

Chemical formula: H2O2

Molecular weight: 34.0 g/mol

Standards: Hydrogen Peroxide Solution (20 Vol) contains not less than 5.0 per cent w/v and
not more than 7.0 per cent w/v of H2O2, corresponding to about 20 times its volume of
available oxygen.

Method of Preparation:

1. It is obtained adding thick paste of barium or sodium peroxide in ice cold water to a
calculated quantity of ice cold solution of sulphuric acid. The insoluble barium sulphate

Chemical reactions:

Na2O2 + H2SO4 → H2O2 + Na2SO4

2. By electrolysis of 50 percent ice cold sulphuric acid. First per disulphuric acid will be
formed which on distillation under reduced pressure gives hydrogen per oxide. The yield of
hydrogen peroxide is 30%. The distillate containing hydrogen per oxide is analysed and is
adjusted to the required strength.

Chemical reactions:

2H2SO4 → H2S2O8

H2S2O8 + 2H2O → 2H2SO4 + H2O2 Description:

• A clear, colourless liquid; odourless

• It decomposes in contact with oxidisable organic matter and with certain metals and also if
allowed to become alkaline

Assay Principle: REDOX TITRATION PERMANGANOMETRIC TITRATION.

The assay method is based on the oxidation-reduction that is redox titration; the assay is
based on the reducing property of the hydrogen per oxide. Simultaneous oxidation and
reduction takes place between hydrogen peroxide and potassium permangate, in presence of

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the acidic media, which is maintained by sulphuric acid, the hydrogen per oxide is oxisidised
to oxygen and permanganate ion is reduced to manganese ion. In this titration potassium
permanganate acts as self indicator, the end point is appearance of permanent pale pink

Chemical reactions:

2KMnO4 + 3 H2SO4 + 5H2O2 → K2SO4 + MnSO4 + 5O2 + 8H2O

Storage: Store protected from light in containers resistant to hydrogen peroxide at a

temperature not exceeding 30°C. If the solution does not contain a stabilising agent, it should
be stored in a refrigerator (2° to 8°C). It should not be stored for long periods

Medicinal uses:

• Anti-microbial agent
• Bleaching agent
• Antidote for phosphorus and cyanide poisoning
Iodine

Chemical formula: I2

Molecular weight: 253.8 g/mol

Standards: Iodine contains not less than 99.5 per cent and not more than 100.5 per cent of
Iodine

Method of Preparation:

Iodine is obtained by natural source, by extracting kelp (seaweed’s ash) with water. The
solution is concentrated to remove salts of sulphate and chloride leaving freely soluble
sodium and potassium iodide in the mother liquor. To this solution sulphuric acid is added to
remove sulphur and sulphides, which gets liberated, from small amount of thio sulphates and
sulphide is allowed to settle down. The mother liquor is decanted and to this solution
manganese di oxide is added and iodine distils over

Chemical reactions:

2NaI + 3H2SO4 + MnO→ MnSO4 + 2NaHSO4 + I2 + 2H2O Description:

• Heavy , bluish-black, rhombic prism or plates having metallic lusture

• Peculiar odour
• Irritant
• It volatilises at ordinary temperature
• Freely soluble in chloroform and ether, soluble in water in presence of potassium
iodide

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Storage: Store in ground-glass-stoppered containers or in earthenware containers with waxed
bungs.

Medicinal uses:

• Counter irritant
• Disinfectant
• Proper thyroid functioning

Preparations of Iodine
• Aqueous iodine solution
• Weak iodine solution
• Strong iodine solution
• Povidone-Iodine solution

Aqueous iodine solution

Synonym: Lugols solution

Standards: It is having 5%w/v of iodine and 10 % w/v of potassium iodide in purified water

Composition:

• Iodine --- 50g

• Potassium iodide --- 100g
• Purified water sufficient to produce-----1000 ml

Method of preparation: Potassium iodide and iodine are first of dissolved in 100 ml of
water with trituration or shaking process. Then the volume is made upto 1000 ml with
purified water.

Description

• Transparent
• Brown liquid,
• Having the smell of iodine
Storage condition: It is preserved in well closed container of glass or plastic which are
resistant to iodine. It is not stored in metallic containers because iodine attacks metal.

Medicinal uses:

• Good source of iodine (internally)

• Externally as germicide, fungicide

Advantages:

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 • Non irritant

Weak iodine solution

Synonym: Iodine tincture or tincture of iodine

Standards: It is having 2%w/v of iodine and 2.5 % w/v of potassium iodide in 50 % alcohol

Composition:

• Iodine --- 20g

• Potassium iodide --- 25g
• Alcohol (50%) to produce-----1000 ml
Method of Preparation: Potassium iodide and iodine are first of dissolved in 100 ml of 50 %
alcohol. Then the volume is made upto 1000 ml with 50 % alcohol

Description:

• Transparent
• Brown liquid,
• Having the smell of iodine
Storage condition: It is preserved in well closed container of glass or plastic which are
resistant to iodine. It is not stored in metallic containers because iodine attacks metal.

Medicinal uses:

• Good source of iodine (internally)

• Externally as germicide, fungicide
• Well known antiseptic

Disadvantages:

• irritant

Strong iodine solution

Standards: It is having 10 %w/v of iodine and 6 % w/v of potassium iodide in 90 % alcohol

Composition:

• Iodine --- 100g

• Potassium iodide --- 60g
• Purified water sufficient----100 ml
• Alcohol (90%) to produce-----1000 ml
Method of Preparation: Potassium iodide and iodine are first of dissolved in 100 ml purified
water. Then the volume is made upto 1000 ml with 90 % alcohol

Description:

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 • Transparent
• Brown liquid,
• Having the smell of iodine
Storage condition: It is preserved in well closed container of glass or plastic which are
resistant to iodine. It is not stored in metallic containers because iodine attacks metal.

Medicinal uses:

• Good source of iodine (internally)

• Externally as germicide, fungicide
• Well known antiseptic

Disadvantages:

• Irritant
Povidone –Iodine solution

It is an aqueous solution of Povidone iodine. It is complex produced by the interaction

between iodine and Povidone (Poly vinyl pyrrolidine). The complex is having about 10 % of
iodine.

Description:

• Yellowish brown, amorphous powder,

• Having a characteristic odour
• Soluble in water and alcohol
• The solution is transparent in nature and has reddish brown colour and faint smell of
iodine
• Its aqueous solution is having acidic pH
Storage: It is kept in a closed container and remains stable.

Medicinal uses:

• Bactericidal
• Disinfection of skin cuts and wounds and even applied on burnt cases also.

Advantages:

• Water solubility
• Nonirritant
• Less toxicity
• Non staining in nature Potassium permanganate

Chemical formula: KMnO4

Molecular weight: 158.0g/mol

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Standards: Potassium Permanganate contains not less than 99.0 per cent and not more than
100.5 per cent of KMnO4
Method of Preparation: On large scale potassium permanganate is prepared by mixing a
solution of potassium hydroxide with manganese di oxide and potassium chlorate. The
mixture is boiled, evaporated to yield the residue which is heated in iron pans until it has
acquired a paste consistency.

Chemical reactions:

3MnO2 + KOH + KClO3 →K2MnO4 + 3H2O+ KCl

Potassium manganate (green) so formed is extracted with boiling water and a current of
chlorine or carbon di oxide or ozonised air is passed in to the liquid until it gets converted to
permanganate. The manganese di oxide so formed is removed continuously so as to prevent
its breaking down to manganate.

Chemical reactions:

6K2MnO4 + 3Cl2 → 6 KMnO4 + 6KCl

The solution of potassium permanganate is drawn off from any precipitate of manganese di
oxide which is then concentrated and crystallised. The crystals are then centrifuged and dried.
Description:

• A dark purple or brownish black, granular powder or dark purple or almost

black slender, prismatic crystals  Having a metallic lustre  Odourless.
• It decomposes on contact with certain organic substances Storage: Store

protected from moisture

Medicinal uses:

• Anti-microbial agent
• Antiseptic in mouth wash
• Anti-dote: Barbiturates, chloral hydrate
• Veterinary practice: antiseptic

Chlorinated lime

Chemical formula: Ca(OCl) Cl

Molecular weight: 142.9 8g/mol

Standards: It contains not less than 30 per cent w/w of chlorine

Synonym: Calcium hypochlorite, Calcium oxychloride, Bleaching powder

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Method of preparation: By action of chlorine gas on calcium hydroxide. Calcium hydroxide
is spread on the 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 step is
carried out at 25oC, thereby minimising the formation of calcium chloride, when absorption
of chlorine gas gets completed, powdered lime is blown into the chamber to absorb the excess
of calcium chlorate.

Chemical reaction:
Ca (OH)2 + Cl2 → Ca(OCl) Cl + H2O

Description
It occurs as a dull white powder having a charteristic odour. When exposed to air, gradually
absorbs moisture and gradually gets decomposed. Slightly soluble in water and alcohol

Assay: Principle: Based on Redox titration, Iodometric titration

The available chlorine in the compound is liberated by the action of acetic acid, then an
equivalent weight of chlorine gas is replaced with iodine by the action of potassium iodide.
The liberated iodine is then titrated against sodium thio sulphate using starch as mucilage.
Until the blue colour changes to colourless

Chemical reactions:

Ca (OCl)Cl + 2CH3COOH →(CH3COOO)2Ca + Cl2 + H2O

Cl2+ 2KI→ I2+ 2KCl

I2+ 2Na2S2O3 → 2NaI + Na2S4O6

Storage: Store in well closed container in a cool place Medicinal
Uses:

• Disinfectant
• Bleaching agent

Boric acid

Chemical formula: H3BO3

Molecular weight: 61.8

Standards: Boric Acid contains not less than 99.5 per cent and not more than 100.5 per cent
of H3BO3, calculated on the dried basis

Synonyms: Borarcic acid, ortho boric acid

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Method of preparation: Boric acid may be prepared by reacting borax (sodium tetra borate
deca hydrate) with a mineral acid, such as Sulphuric acid
Na2B4O7 +H2SO4 + 5H2O → Na2SO4 + 4H3BO3 Description:

• A white, crystalline powder or colourless shiny plates unctuous to the touch or white
crystals
• Odourless
• Slightly acidic and bitter in taste
• Stable in air
• Weak acid pKa=9.19

Storage: Store protected from moisture

Medicinal uses:

• Anti-microbial agent: weak germicide

• Local anti-infective
• Aqueous solution : eye wash and mouth wash
• Dusting powder

Astringents

These are the compounds, which bring about the protein precipitation. They are usually
applied to damage skin topically or to mucous membrane of the GIT including the mouth.
The precipitated protein and astringent form a protective layer on the surface.

Astringents have low cell permeability so that the action is limited to the cell surface and the
interstitial spaces. The action does not result in the death of the cell, only the permeability of
the cell membrane is reduced. The protein precipitation brought about by the astringents is
due to the presence of metallic ions having larger charge or strong electrostatic force. The
metal would form complex with various polar groups present on the protein or enzyme. This
complexation of important functional groups at the site of protein or an enzyme causes a
drastic change in the properties of the protein.

Astringents are therapeutically used as:

1. Styptic action, to stop bleeding from small cuts by promoting coagulation of blood and
constricting small capillaries.

2. To check diarrhea.

3. Antipersistant to decrease sweating by constricting pores at the skin surface.

4. To reduce inflammation by restriction of blood supply to the surface of mucous membrane.

5. To promote healing and toughen the skin.

6. To possess deodorant properties.

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The inorganic compounds having astringent properties are salts of aluminum, zinc,
manganese, iron, bismuth, silver, zirconium, etc. Of these the compound to be studied in
detail are alum and zinc sulphate.

Zinc sulphate

Chemical formula: ZnSO4, 7H2O

Molecular weight: 287.5 g/mol

Standards: Zinc Sulphate contains not less than 99.0 per cent and not more than 104.0 per
cent of ZnSO4, 7H2O.

Method of Preparation: For Pharmacopeial requirement, it is prepared by digesting metallic

zinc granules in dilute sulphuric acid. The solution is filtered to separate the undissolved
metallic zinc. The filtrate is treated with chlorine to oxidize any ferrous sulphate impurity into
ferric sulphate which is then precipitated by hydroxide and removed by filtration process.
Then the filtrate is concentrated to get the crystals of zinc sulphate.

Chemical reactions:

Zn + H2SO4+ 7 H2O→ ZnSO4 +7H2O + H2 ↑

Description:

• A Colourless, transparent crystals or a white, crystalline powder

• Odourless • Efflorescent.
• Very soluble in water and glycerine and insoluble in alcohol Storage: Store protected

from moisture, in non-metallic containers.

Medicinal uses:

• Astringent
• Emetic

Alum (potash alum, aluminium potassium sulphate),

Chemical Formula: 2KAl (SO4)2, 12H2O

Molecular weight: 474.4 or 928 g/mol

Standards: It contains not less than 99.5 per cent

Description:
• A Colourless, transparent crystals or a white, crystalline powder
• Sweet astringent taste
• Heated to 200oC, looses its water of crystallisation and becomes anhydrous

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 • Soluble in water, insoluble in acetone and alcohol

Method of preparation: It is prepared by adding concentrated solution of potassium sulphate

to a hot solution of an equimolecular proportion of aluminum sulphate. The concentrated
solution is cooled and characteristic octahedral crystals separate

Chemical reaction:
K2 SO4 + Al2( SO4)3 + 24 H2O →2KAl(SO4)2 . 12H2O
Storage: Alum should be stored in well-closed container.

Medicinal and Pharmaceutical Uses:

• Alum is used in many subunit vaccines as an adjuvant to enhance the body's response
to immunogens. Such vaccines include hepatitis A, hepatitis B, and DTaP.
• Alum in powder or crystal form, or in styptic pencils, is sometimes applied to cuts to
prevent or treat infection.
• Alum is commonly cited as a home remedy for canker sores.
• Preparations containing alum are used by pet owners to stem bleeding associated with
animal injuries caused by improper nail clipping.
• Alum is listed as an ingredient of some brands of toothpaste or toothpowder.
• Alum powder dissolved in five parts water has been used to shrink hemorrhoids and
stop them from bleeding.

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