Pharmaceutical

Inorganic
Chemistry
Ms. Chaitrali Thatte
Assistant Professor
VESCOP
GASTROINTESTINAL AGENTS
Gastrointestinal Agents are used in the treatment of GIT
disorders such as achlorhydria, hyperacidity, diarrhea &
constipation
CLASSIFICATION

• Acidifiers
• Antacids
• Cathartics
• Antimicrobials
ACIDIFIERS
Achlorhydria defined as the condition in which there is no secretion of
HCl in stomach

Symptoms

• Frequent bowel movement

• Mild diarrhea

• Abdominal pain

• Sensitivity to spicy food

Dilute hydrochloric acid is used for treatment of achlorhydria.

It increase gastric HCl level
Types of Patients with Achlorhydria

TYPE 1- Patients who don’t produce HCl even after Histamine

release due to severe permanent damage to gastric glands

They lack the ability to produce HCl, even after histamine

stimulation, no acid is produced.

TYPE 2- Patients who respond to histamine stimulation and

produce HCl. Acid producing cells exist, but they are suppressed
• HCl is released from Parietal cells

• Histamine is released from enterochromaffin-like ECL cells,

which are present in the stomach lining. ECL cells release
histamine when stimulated.

• When histamine is released, it binds to H2 receptor on these

parietal cells.

• This activates H+/ K+ ATPase proton pump, which

stimulates HCl secretion
Properties of HCl

Property Description
Appearance Colorless liquid
Odour Pungent/ irritating
Taste Acidic
pH 1-2
Specific Gravity 1.02
Soluble Very Soluble in water
METHOD OF PREPARATION
1. Laboratory Preparation
HCl is theoretically prepared by reacting a chloride salt
with a strong acid.
Reaction-
𝐍𝐚𝐂𝐥 + 𝑯𝟐 𝐒𝑶𝟒 → 𝐍𝐚𝐇𝐒𝑶𝟒 + 𝐇𝐂𝐥 ↑

Sodium chloride reacts with concentrated sulfuric acid.

Hydrogen chloride gas is released.
This gas can be dissolved in water to make
hydrochloric acid.
2. Industrial Preparation (Commercial Method)
Industrially, HCl is produced by:

A. Direct Combination of Elements-

Hydrogen and chlorine gases react in a controlled chamber. The HCl gas
formed is absorbed in water to produce hydrochloric acid
Reaction- H2+Cl2→2HCl

B. As a By-product in Chlorination Reactions-

Many large-scale chemical processes (e.g., making PVC) release HCl
gas
Diluted HCl N.F.
• Dilute HCl NF refers to a hydrochloric acid solution that is specified
by the National Formulary (NF), a compendium of pharmaceutical
standards.
• A common NF-grade solution is 10% (w/v) dilute hydrochloric acid,
which contains 9.5 to 10.5 grams of HCl per 100 mL
Identification Tests of HCl
Test Procedure Observation

Litmus Test Place moist blue litmus The blue litmus paper will
paper in contact with the turn red, indicating an
gas or solution. acidic substance.

Silver Nitrate Test Add a few drops of silver A white precipitate of

nitrate solution to the HCl silver chloride (𝐴𝑔𝐶𝑙) will
solution, preferably form
acidified with nitric acid to
prevent other ion
interference.

pH Dip pH paper into the The pH reading will be

solution or use a pH meter. very low (typically below
1-2)
USES of HCl
• Digestive aid (very dilute HCl): Used in some
medicines to treat Achlorhydria (low stomach acid)
• pH adjustment in formulations: Helps maintain
stability of drugs.
• Used to produce gelatin and corn syrup
• Helps in making vinyl chloride monomer
• Acts as a catalyst in many reactions.
AMMONIUM CHLORIDE
• Ammonium Chloride, U.S.P. XVIII (NH₄Cl)
• Mol. Wt. 53.49
• Ammonium muriate, sal ammoniac, salmiac

Property Description
Appearance Colorless crystals
Odour Odorless
Taste Cool, saline
pH 4.5-5
Specific Gravity 1.53
Soluble Very Soluble in water and
glycerin
Ammonium Chloride as an Acidifier
• Ammonium ion plays an important role in the maintenance of the
acid-base equilibrium of the body
• Ammonium chloride dissociates in the body to form ammonium ions
(NH₄⁺) and chloride ions (Cl⁻)
NH₄Cl → NH₄⁺ + Cl⁻

• The ammonium ion (NH₄⁺) is transported to the liver where it is

converted to urea through urea cycle
NH₄⁺ + CO₂ → Urea + H⁺

• During this conversion, hydrogen ions (H⁺) are released into the
bloodstream, along with the formation of urea which increases
acidity
Fate of Chloride
• The chloride ion (Cl⁻) replaces bicarbonate ions (HCO₃⁻) in
the blood (Chloride Shift)

• Since bicarbonate is the main base in the body, loss of

bicarbonate decreases the pH, causing systemic
acidification

• Increase in H⁺ ions and decrease in bicarbonate leads to

lowering of blood pH, making ammonium chloride an
effective systemic acidifier
Ammonium Chloride as an Expectorant
• Ammonium chloride acts as an expectorant by increasing the secretion
of respiratory tract fluids.

• After administration, ammonium ion (NH₄⁺) is converted in the liver

to urea, releasing hydrogen ions (H⁺).
• The released H⁺ ions lower the pH of the blood slightly, producing
systemic acidosis.

• This mild acidosis stimulates the respiratory center and increases

bronchial secretions.

• The increased fluid in the airways becomes thin and loosens thick
mucus, making it easier to cough out

• Ammonium chloride increases mucus secretion and reduces viscosity,

helping in the easy expulsion of sputum from the respiratory tract
Assay of Ammonium Chloride
Aim- To perform assay of ammonium chloride IP 1996

Standards- Ammonium Chloride contains not less than 99.00% and not more
than 100.5% of NH4Cl

Chemicals Required: Ammonium chloride ,formaldehyde solution, potassium

iodide, 0.1 M sodium hydroxide solution

Theory- This is an alkalimetric titration

NH4Cl+H2O→NH4OH + HCl
NH4OH+ HCHO→ CH2=NH + 2H2O
HCl+ NaOH → NaCl + H2O
PROCEDURE-
• Weigh 0.1gm of NH4Cl dissolve in 20 ml of H2O and add a mixture
of 5 ml of previously neutralized formaldehyde solution and 20 ml
water
NH4Cl+H2O→NH4OH + HCl
NH4OH+ HCHO→ CH2=NH + 2H2O

• After 2 minutes the contents of the conical flask are titrated against
0.1N NaOH using phenolphthalein as indicator
HCl+ NaOH → NaCl + H2O

• End point is the appearance of permanent pale pink color

• Each ml of 0.1N NaOH is equivalent to 0.005349 gm of NH4Cl

RESULT: The percentage purity of ammonium chloride in the given

sample is % w/w
ANTACIDS
Antacids are weakly basic substances that neutralize
excess gastric hydrochloric acid (HCl) in the stomach,
providing relief from acidity, heartburn, indigestion, and
peptic ulcer pain

Acid Neutralizing Capacity-The amount of HCl (in mEq)

neutralized by an antacid.
Higher ANC → more effective antacid.
Regulated by USP standards
Ideal Properties of Antacids-

• Neutralize acid rapidly and effectively

• Not cause systemic alkalosis
• Show minimum gas formation
• Not cause constipation or diarrhea
• Be palatable and non-toxic
• Have high acid-neutralizing capacity (ANC)
Classification
A. Systemic Antacid- These antacids are water soluble and absorbed
into bloodstream. They can cause systemic alkalosis. Eg- Sodium
bicarbonate
B. Non-Systemic Antacids-Water insoluble, fewer systemic effects
Eg- Aluminium-containing antacids Al(OH)₃, Magnesium containing
antacids Mg(OH)₂ , Calcium containing antacids CaCO₃
C. Combination of Antacids- Different antacids cause opposite
gastrointestinal effects for eg,- Mg(OH)₂ + Al(OH)₃
• Magnesium salts → cause diarrhoea
• Aluminium salts → cause constipation
To cancel these effects and to improve speed and duration of action
A. Systemic Antacid
• Absorbed into bloodstream → risk of alkalosis
1. Sodium Bicarbonate (NaHCO₃ , Sodium hydrogen
carbonate, Baking soda)
NaHCO₃, Mol wt-84.01 g/mol
• Rapid onset of action
• Sharp increase in pH up to 7 or above
• Short duration
• Produces CO₂ → gas, belching
• Systemic alkalosis is possible
• Rarely used now
Usual Dose- 300 mg to 2g, four times daily
Usual Dose Range- 300 mg to 16g daily
PROPERTIES

Property Description
Appearance White crystalline powder

Odour Odorless
Taste Slight salty taste

pH 8 to 8.5
Soluble Very Soluble in water and
insoluble in alcohol
METHOD OF PREPARATION
A. Industrial (Solvay Process)-
Ammonia and carbon dioxide is passed into saturated NaCl solution:

NaCl + NH₃ + CO₂ + H₂O → NaHCO₃↓ + NH₄Cl

Sodium Ammonia Carbon Sodium
Chloride dioxide bicarbonate

Sodium bicarbonate is obtained as a precipitate

Filtration → Washing → Drying → NaHCO₃ obtained
REACTIONS
[Link] Hydrochloric acid
NaHCO₃ + HCl → NaCl + CO₂↑ + H₂O
Sodium Sodium
Bicarbonate Chloride

2. With Sulfuric acid

2 NaHCO₃ + H₂SO₄ → Na₂SO₄ + 2 CO₂↑ + 2 H₂O
Sodium Sulphuric Sodium
Bicarbonate acid Sulphate
3. Thermal Decomposition

2 NaHCO₃ → Na₂CO₃ + CO₂ + H₂O

Sodium Sodium
Bicarbonate Carbonate

4. With Bases
NaHCO₃ + NaOH → Na₂CO₃ + H₂O
Sodium Sodium Sodium
Bicarbonate Hydroxide Carbonate
USES OF SODIUM BICARBONATE
• Systemic antacid
• Component of effervescent tablets
• Source of CO₂ in baking powder
• Mild antiseptic
• Used in sodium bicarbonate injection (IV) for metabolic
acidosis
ASSAY OF SODIUM BICARBONATE
Standards- Sodium Bicarbonate contains not less than
99.00% and not more than 101.5% of NaHCO₃
Procedure- 1gm of Sodium Bicarbonate is weighed
accurately and dissolved in 20ml of water

Resultant mixture is titrated with 0.5N Sulphuric acid

using methyl orange as an indicator

Each ml of 0.5N H₂SO₄ = 0.042g of NaHCO₃

 ALUMINIUM HYDROXIDE GEL USP Al(OH)₃
• Molecular formula- Al(OH)₃
• Molecular wt: 77.99 g/mol
Aluminium hydroxide is recognized by the current U.S.P. in two physical
forms plus one dosage form

1. Aluminium Hydroxide Gel U.S.P. XVIII (Amphogel®) is a white, viscous

suspension, from which small amounts of clear liquid may separate on
standing
It has a pH between 5.5 and 8.0

2. Dried Aluminium Hydroxide Gel U.S.P. XVIII

Fine, odourless, tasteless, amorphous powder, insoluble in water and soluble in
dilute mineral acids and solutions of fixed alkali hydroxides.

The dried gel is also official as dried Aluminium Hydroxide Gel Tablets U.S.P.
XVIII (Amphogel® tablets)
Both forms are assayed in terms of their aluminum oxide (Al₂O₃) content and
their acid neutralizing capacity
PROPERTIES

1. Physical Properties-
• White, viscous, gelatinous mass
• Odorless, tasteless
• Insoluble in water and alcohol
• Slightly soluble in dilute mineral acids and strong alkalis

2. Chemical Properties-
• Amphoteric (acts as acid or base)
METHOD OF PREPARATION
Aluminium hydroxide gel is prepared by double decomposition of
aluminium salts with alkali.
Method 1: From Aluminium Sulphate
Al2​(SO4​)3​ + 6NH4​OH → 2Al(OH)3​↓ + 3(NH4​)2​SO4
Aluminium Sodium
Sulphate Hydroxide
The precipitated Al(OH)₃ is washed and kept as hydrated gel.

Method 2: From Aluminium Chloride

AlCl3​ + 3NH4​OH → Al(OH)3​↓ + 3NH4​Cl
Aluminium Sodium Aluminium
Chloride Hydroxide Hydroxide
REACTIONS
1. Reaction with Acids (neutralization):
Al(OH)3 + 3HCl → AlCl3 + 3H2O
Aluminum Aluminium
Hydroxide Chloride

2. Reaction with Bases (forms aluminates):

Al(OH)3 + NaOH → NaAlO2 + 2H2O
Aluminum Sodium Sodium
Hydroxide Hydroxide Aluminate

[Link] with Carbonates:

Slowly reacts with CO₂ from air forming basic aluminium carbonate.
USES OF ALUMINIUM HYDROXIDE GEL
• It is non systemic or non absorbable antacid

• Externally it is used as mild astringent

• Used in the treatment of diarrhea & cholera

• Externally used as dusting powder

MAGNESIUM HYDROXIDE MIXTURE Mg(OH)2
• Magnesium hydroxide aka (Milk of Magnesia)
• Molecular formula: Mg(OH)2
• Molar wt: 58.32 g/mol

• Magnesium hydroxide mixture is an aqueous suspension of magnesium hydroxide,

containing about 7–8% w/v Mg(OH)₂.
• It appears as a white, smooth, milky suspension.
• Usual Dose Ranges- antacid: 300 to 600 mg
cathartic: 2 to 4 g

Occurrence-
• Magnesia Tablets, U.S.P. XVIII
• Magnesia and Alumina Oral Suspension, U.S.P. XVIII
• Magnesia and Alumina Tablets, U.S.P. XVIII
• Milk of Magnesia, U.S.P. XVIII
PROPERTIES
• Appearance - White amorphous powder
• Odor - Odorless
• Taste - Tasteless
• Solubility – Soluble in dilute acids, insoluble in water
and alcohol
METHOD OF PREPARATION
1. From Magnesium Sulphate
MgSO4 + 2NaOH → Mg(OH)2↓ + Na2SO4
Magnesium Sodium Magnesium Sodium
Sulphate Hydroxide Hydroxide Sulphate

Wash to remove sodium sulfate.

Suspend the precipitate in purified water → Milk of Magnesia.
USES
• Neutralizes excess gastric acid
• Laxative (saline purgative) at higher doses effect
• Used in hyperacidity, indigestion and occasional constipation
• Commonly combined with aluminium hydroxide to balance bowel
effects
ALUMINIUM HYDROXIDE GEL+MAGNESIUM
HYDROXIDE COMBINATIONS
• Aluminum Hydroxide Gel-Magnesium Hydroxide Combinations (Aldrox®,
WinGel®, Maalox®, Creamalin®)
• These products are all results of attempts to obtain a product that is not
constipative or laxative
• The U.S.P. recognizes two dosage forms, a suspension and a tablet. For
each dosage form, either aluminium hydroxide gel or magnesium hydroxide
may predominate
• Alumina and Magnesia Oral Suspension U.S.P. XVIII contains the
equivalent of 4% aluminum oxide (Al₂O₃) and 2% magnesium hydroxide
[Mg(OH)₂]
• In contrast, Magnesia and Alumina Oral Suspension U.S.P. XVIII contains
the equivalent of 2.2% aluminum oxide and 3.8% magnesium hydroxide
• A similar type of relationship holds for Alumina and Magnesia Tablets U.S.P.
XVIII and Magnesia and Alumina Tablets U.S.P. XVIII
DOSE AND DOSE RANGE

• Suspension
Usual Dose: 15 ml four to six times a day
Usual Dose Range: 5 to 120 ml daily

• Tablets
Usual Dose: 1 or 2 tablets four to six times a day
Usual Dose Range: 1 to 4 tablets up to twelve times
daily
 SALINE CATHARTICS / LAXATIVES
Classification-
1. Bulk-forming Cathartics
• Increase bulk by absorbing water.
Examples: Isapgol, Agar, Methylcellulose
2. Emollient/Lubricant Cathartics
• Soften stool; mild action.
Examples: Liquid paraffin (mineral oil)
3. Osmotic / Saline Cathartics
They Increase osmotic pressure in the intestine
•Water is retained in bowel
•Increased volume causes distension
•Stimulates peristalsis
•Leads to defecation
4. Stimulant Cathartics- They increase the bowel
movement by local irritation of intestinal mucosa
Eg- Senna, Castor oil
Difference between Purgatives
and Laxatives
USES
• Constipation
• Preparation for colonoscopy/surgery
• Removal of poisons (to empty bowel)
• To reduce strain in cardiac patients (stool softeners)
• To maintain soft stools in hemorrhoids and anal fissure
MAGNESIUM SULPHATE
• Formula: MgSO₄·7H₂O
• Molecular weight: 246.4 g/mol
• Common name: Epsom salt
• Category: Saline Cathartic
• Dose : 10 to 15g
• Dose Range:10 to 30g daily

PROPERTIES-
• Colorless, transparent crystals or granular crystalline powder
• Odorless, cooling saline taste
• Bitter saline taste
• Melts at about 150°C (loses water of crystallization)
• Very soluble in water; freely soluble in boiling water; slightly soluble in
alcohol
METHOD OF PREPARATION
• Laboratory Preparation
1. From Magnesium Carbonate:
MgCO3 + H2​SO4 → MgSO4 + H2O + CO2↑
Magnesium Magnesium
Carbonate Sulphate

[Link] Magnesium Oxide

MgO + H2SO4 → MgSO4 ​+ H2​O
Magnesium Magnesium
Oxide Sulphate

Solution is crystallized to obtain MgSO₄·7H₂O

Mechanism of Action of Magnesium Sulphate
• Osmosis is the movement of water from a region of low solute
concentration → high solute concentration across a semipermeable
membrane
• In the intestine, the membrane = intestinal wall
• Osmotic pressure depends on the amount of dissolved particles
(ions/solutes).
• More dissolved solute → higher osmotic pressure
• Fewer dissolved solutes → lower osmotic pressure
• MgSO₄ dissolves into two ions: Mg²⁺ and SO₄²⁻
• These ions increase the solute concentration inside the intestinal
lumen.
• So, inside the lumen: Solute concentration ↑, Osmotic pressure ↑
• Blood has lower solute concentration than the lumen after
MgSO₄ enters the intestine
• So: Osmotic pressure in lumen > Osmotic pressure in blood
• This means: The lumen is “more concentrated” with solutes
• It “pulls” water from the blood.
• Water always moves from lower osmotic pressure → higher
osmotic pressure.
• So, water moves: Blood (low OP) → Intestinal lumen (high
OP)
• This is why the lumen fills with water → water retention →
purgative effect.
More water in the intestine causes-

• Softens the stool

• Increases bulk
• Stimulates peristalsis
• Produces cathartic (purgative) effect
Reactions
1. Reaction with Sodium Hydroxide
Forms Magnesium Hydroxide (white precipitate):
MgSO4 + 2NaOH → Mg(OH)2↓ + Na2SO4
Magnesium Sodium Magnesium
Sulphate Hydroxide Hydroxide

2. Reaction with Ammonium Hydroxide

Forms a white precipitate of Mg(OH)₂:
MgSO4 + 2NH4OH → Mg(OH)2↓ + (NH4)2SO4
Magnesium Ammonium Magnesium
Sulphate Hydroxide Hydroxide
3. Reaction with Barium Chloride
Forms white precipitate of Barium Sulphate:
MgSO4 + BaCl2 → BaSO4↓ + MgCl2
Magnesium Barium Barium
Sulphate Chloride Sulphate

4. Reaction with Silver Nitrate

MgSO4 + 2AgNO3 → Ag2SO4↓ + Mg(NO3)2
Magnesium Silver Silver Magnesium
Sulphate Nitrate Sulphate Dinitrate
USES
• Cathartic (saline purgative): Produces rapid bowel evacuation.
• Anticonvulsant: In seizures (MgSO₄ injection)
• Used in Lotions, eye baths, gargles (isotonic solutions)
• As a stabilizer in some formulations
• Used in preparation of magnesium compounds like Mg(OH)₂
• In dyes, tanning, and textile processes
Sodium Orthophosphate
When used as a cathartic, the salt commonly used is:
• Sodium dihydrogen phosphate (NaH₂PO₄) &
• Disodium hydrogen phosphate (Na₂HPO₄)
• These two together are often called sodium phosphate
cathartic salts.
Disodium Hydrogen Phosphate N.F. XII
Disodium hydrogen phosphate (Na₂HPO₄) is a saline cathartic.
It is a phosphate salt of phosphoric acid, moderately alkaline and
freely soluble in water

MOA- Same as Magnesium Sulphate

Onset: 30 min – 3 hours

Dose- 4 g
Dose Range- 4 to 8g
Produces watery stools (purgative effect)
Stronger effect than ordinary laxatives
Properties
• Physical Properties
• Appearance: White, crystalline powder
• Taste: Saline
• Odor: Odorless
• Solubility:Freely soluble in water, Insoluble in alcohol
• pH: Aqueous solution is mildly alkaline 9 to 9.5(due to
HPO₄²⁻)
Method of Preparation
From Phosphoric Acid and Sodium Carbonate-
• Phosphoric acid (H₃PO₄) is partially neutralized with sodium
carbonate (Na₂CO₃)

Na2​CO3​ + H3​PO4 ​→ Na2​HPO4 ​+ CO2​↑ + H2​O

Disodium
Hydrogen
Phosphate

•Reaction releases CO₂ gas (effervescence).

•Continue addition until pH becomes slightly alkaline (≈ pH 8).
•Evaporate the solution → crystallize → dry → Na₂HPO₄ obtained
USES

• Bowel cleansing before surgery or colonoscopy

• Acute constipation
• To remove ingested toxins (rapid bowel emptying)
• As a phosphate source in certain formulations
• Component of sodium phosphate enema preparations
Thank You!