Gastrointestinal agents | Pharmaceutical Chemistry

Gastrointestinal agents, Acidifiers, Antacids, Protective & Adsorbent, Pharmapedia, ThePharmapedia

The Gastrointestinal (GI) Tract includes the mouth, stomach, small intestine (duodenum, jejunum, and ileum), large intestine (cecum and colon), rectum, anus, and its accompanying exocrine glands (the salivary glands, the pancreas, and the gallbladder).

Drugs affecting the GI system are used in the treatment of Gastric Acidity, Peptic Ulcers, and Gastro Esophageal Reflux Disease (GERD), Bowel Motility Disorders (gastroparesis [delayed gastric emptying due to partial paralysis of the stomach muscles], constipation, and diarrhea), and for the treatment of nausea and vomiting

Classification of Inorganic Gastrointestinal agents

GI agents are classified into four major classes:

  1. Acidifiers
  2. Antacids
  3. Protective & Adsorband
  4. Saline cathertic
Acidifying agents, Dilute hydrochloric acid, antacid,  Sodium bicarbonate, aluminium hydroxidegel, aluminium phosphate, calcium carbonate, magnesium carbonate, magnesium trisilicate, magnesium oxide, Protectives and Adsorbent, Bismuth subcarbonate, Kaolin, Saline cathartics, Sodium Pottassium tartate and magnesium sulphate, Pharmapedia, ThePharmapedia
Classification of Gastrointestinal agents

Acidifiers

These are the inorganic substances that either produce or increase acid. These Chemicals increase the level of gastric acid in the stomach where ingested there by decrease the stomach pH.

It is broadly classified into 4 classes

  1. Gastric acidifiers
  2. Urinary acidifiers
  3. Systemic acidifiers
  4. Acid

Gastric acidifiers

These are drug which are used in increases the acidity of stomach. These agents used in patients suffering from achlorhydria or hypochlorhydria or Hypochlorhydria.

Hypochlorhydria

Whenever inadequate secretion of acid takes place in the stomach, this causes achlorhydria or hypochlorhydria.

Acidifying agents/acidifiers are used in treatment of Hypochlorhydria

Urinary acidifier

These are the drugs which are used to remove acidic urine from the body or to maintain the pH of urine. These acidifier are used to cure some type of urinary track infection.
Example:-

Systemic acidifier

Systemic HD file are the trip which are able to neutralized the alkaline body fluid or maintain the pH of all part of the body. It is used to treat patient suffering from systemic alkalosis.

Acid

These are used as Pharmaceutical aids in the preparation of medicaments.
Example: HCL

ANTACID

These are drugs used for neutralizing excess acid in the stomach.

Classification
(i) Systemic antacids.
(ii) Non-systemic antacids.

(i) Systemic Antacids

They are used to reduce the acidity of blood.

Eg. Sodium bicarbonate in sodium citrate.

SODIUM BICARBONATE

M.F. NaHCO3; Syn: Baking Soda

PREPARATION

Laboratory Method

It is prepared by passing CO2 gas through a solution of sodium hydroxide. The solution is concentrated to get the product.
2NaOH + CO2 → Na2 CO3 + H2O
Na2CO3 + H2O + CO2 → 2 NaHCO3

Industrial Method

Solvay Process
Brine solution (NaCl) is saturated with ammonia (to remove impurities). The solution is filtered, CO2 is passed through the solution. The precipitate is filtered and dried.
H2O + CO2 → H2CO3
NH3 + H2CO3 → NH4HCO3
NaCl + NH4HCO3 NaHCO3 + NH4Cl

Properties

(i) White crystalline or amorphous powder having a saline taste.
(ii) It is freely soluble in water.
(iii) Practically insoluble in alcohol.
(iv) It gives an effervescence with acids.
(v) Its solution is alkaline in nature.
(vi) When heated, it gives sodium carbonate, CO2 and water

2NaHCO3 → Na2CO3+ H2O + CO2

Assay:

Acid-Base Titration Method
Weighed amount is dissolved in water and titrated with sulphuric acid using methyl orange as indicator.
2NaHCO3 + H2SO4 → Na2 SO4 + 2CO2 + 2H2O.

Storage: It is stored in well closed container.

Use:
(i) Used in systemic acidosis.
(ii) Local application for burns, insect bites etc.
(iii) Used as a constituent in ear drops to soften and remove wax.

(ii) Non-Systemic Antacids

They are used to reduce gastric acidify. (Not absorbed into the systemic circulation).

  • Example:
    • Aluminium hydroxide
    • Magnesium trisilicate
    • Magnesium hydroxide
    • Magnesium oxide
    • Aluminium phosphate
    • Calcium carbonate
ALUMINIUM HYDROXIDE GEL

It is an aqueous suspension of hydrated aluminium oxide together with varying amounts of basic aluminium carbonate. It contains aluminium oxide, glycerin, sucrose or saccharin as a sweetening agent, peppermint oil as a flavouring agent and sodium benzoate as a preservative.

Preparation
It is prepared by the reaction of an aluminium sulphate or aluminium chloride with sodium carbonate or sodium bicarbonate. The precipitate of aluminium hydroxide is collected, washed and resuspended in water and finally homogenized.

3Na2 CO3 + 3H2O → 3NaHCO3 + 3 NaOH
AlCl3 + 3NaOH + H2O → 3 NaCl + Al(OH)3. 3H2O
2NaHCO3 → Na2CO3 + H2O + CO2

Properties

  1. It is a white viscous suspension.
  2. A clear liquid gets separated when it is kept standing for sometime.

Assay

Complexometric Titration: Weighed amount is dissolved in hydrochloric acid by warming. Excess of std EDTA is added. The mixture is neutralized by adding 1 N NaOH. This is warmed on a water bath for half an hour (to ensure complexation between aluminium and EDTA). Then hexamine is added (to maintain alkaline pH) and the excess of EDTA is back titrated with std lead nitrate using xylerol orange as indicator.

Use: As an antacid; Since aluminium salts produce constipation, and are therefore generally administered along with magnesium salts to counteract this effect.

ALUMINIUM PHOSPHATE

It consists mainly hydrated aluminium ortho-phosphate (AlPO4).

Preparation

It is prepared by interaction between aqueous solutions of aluminium chloride and sodium phosphate. The soluble salt is filtered and dried.

Properties

  1. White powder.
  2. Insoluble in water, ethanol and alkali hydroxides.
  3. Soluble in dilute mineral acids.

Assay: (Complexometric Titration)

Weighed amount is dissolved in HCl, then excess EDTA is added. The solution is made just alkaline. After boiling it for 5 mimutes, ammonium acetate and glacial acetic acid are added. Then the pH is adjusted to 4.5 and titrate with zinc chloride (ZnCl2).

Use:

  • Antacid
  • Adsorbent for bacterial toxoids
CALCIUM CARBONATE

M.F. (CaCO3); Syn: Precipitated chalk

Occurrence: In nature, it is found as chalk, marble, limestone, aragonite and calcite (one of the main constituents of corals, pearls and shells).

Preparation (Commercial Method)

It is obtained by mixing the boiling solutions of calcium chloride and sodium carbonate.
CaCl2 + Na2 CO3 → CaCO3  + 2 NaCl

The precipitate is collected, washed with boiling water (until it free from chloride ions) and dried.

Properties

  1. It occurs as fine, white, micro-crystalline powder.
  2. It is odourless and tasteless.
  3. It produces constipation.
  4. It is almost insoluble in water and alcohol.
  5. Calcium carbonate neutralizes acids with effervescence.

CaCO3 + 2HCl → CaCl2 + CO2  + H2O

Assay:

Complexometric Titration
Weighed amount is dissolved in HCl. Then the pH is adjusted to 12 by NaOH. Then it is titrated with EDTA using murexide and napthol green mixture as indicator to a deep blue color end point.

Use:

  1. Externally as dentrifice.
  2. Internally as an antacid.
    Generally it is administered along with magnesium salts (Laxative).
MAGNESIUM CARBONATE

M.F.: 3Mg CO3. Mg(OH)2. 5H2O
It occurs in nature as magnesite (MgCO3) and dolomite (MgCO3. CaCO3).

Preparation
It is obtained by the double decomposition from magnesium sulphate and sodium carbonate. They are dissolved separately in water and the solutions are mixed. The residue is filtered and washed with water until it becomes free from sulphate ions.
MgSO4 + Na2CO3 → MgCO3  + Na2SO4

Properties

  1. It is a white granular powder.
  2. It is odourless and tasteless.
  3. When heated to redness, it gets converted to MgO, losing CO2 and H2O.
    3MgCO3. Mg(OH)2. 4H2O → 4 MgO + 3CO2 + 5H2O

Assay
It is assayed by complexometric titration. Weighed sample is dissolved in dilute HCl small amount of NaOH solution is
added. Then it is titrated with EDTA using murexide as indicator.

Use: Antacid & Laxative

MAGNESIUM TRISILICATE

Formula: 2MgO. 3SiO2. 3H2O
Syn: Hydrated Magnesium silicate

This compound is having magnesium oxide and silicon oxide with varying proportions of water of crystallization.

Preparation
It is obtained from sodium silicate and magnesium sulphate. The magnesium trisilicate is precipitated out by slowly running a solution of magnesium sulphate into a solution of sodium silicate. The precipitate is filtered, washed and dried.

Properties

  1. White fine powder.
  2. It is odourless and tasteless.
  3. It is insoluble in water and alcohol.

Assay

It is assayed for magnesium oxide by conversion to magnesium chloride by complexometric titration and for silicon dioxide by gravimetric method.

For Magnesium Oxide (MgO)
It is done by complexometric titration. Weighed sample is dissolved in hydrochloric acid, small amount of NaOH solution is added. Then it is titrated with 0.05 M disodium edetate using Murexide indicator.

For Silicon dioxide (SiO2)
To the weighed sample, sulphuric acid is added and filtered. The insoluble SiO2 is washed until free from sulphate and ignited for 5 minutes, cooled and weighed.

Use:
Antacid, adsorbent

MAGNESIUM OXIDE

M.F. MgO

There are two varieties of magnesium oxide are available.

  1. Light MgO
  2. Heavy MgO

Heating light or heavy magnesium carbonate, corresponding light or heavy magnesium oxide is obtained.
MgCO3 MgO + CO2 (gas)

Properties

  1. It is a white powder.
  2. It is odourless.
  3. It is insoluble in water and alcohol.
  4. It is soluble in dilute acids.

Assay: By Complexometric Titration

Weighed sample is dissolved in dilute hydrochloric acid. Small amount of strong ammonia – ammonium chloride solution is added, then it is titrated with 0.05 m EDTA using mordant black II mixture as indicator.

Use: Antacid and Laxative

Combinations of Antacid

Preparations

Antacid preparations are formulated with one more than one antacid as combinations to counteract the side effect of one by another or to be used for specific conditions.

(i) Aluminium hydroxide gel – Magnesium hydroxide combination.
Preparation: Available as oral suspension and tablets.
Adv: Since aluminium salts causes constipation, this effect is balanced by laxative effect of magnesium.

(ii) Simethicone containing antacids
It is formulated along with aluminium hydroxide gel and magnesium hydroxide.
It is available as oral suspension and tablet.
Advantage: Simethicone relieves flatulence.

(iii) Aluminium hydroxide gel – magnesium trisilicate combination
It is available as oral suspension and tablet.
Advantage:
Magnesium trisilicate has a protective effect.

PROTECTIVES AND ADSORBENTS

  1. They are generally insoluble.
  2. Non-toxic
  3. Chemically inert
  4. They cover skin or mucous membrane from irritants.

Protectives

Definition : Chemically inert substance used to form a protective layer in GIT.

Adsorbents
Chemically inert substance used for removing toxic substances from GIT.

LIGHT KAOLIN I.P.

M.F : Al2O3. 2SiO2. 2H2O

Preparation:

It is prepared from the native clays, available as deposits in earth.

Procedure

  1. Suspension of clay is prepared in water.
  2. Larger particles (quartz, mica) are removed by elutriation.
  3. Upon successive treatment with sodium pyrophosphate and HCl (to remove acid soluble and basic soluble impurities) and finally subjected to evaporation gives the fine particles of Kaolin.

Properties

  1. It is a light white powder, soft to touch.
  2. Insoluble in water, mineral acids and organic solvents.

I.P. includes two varieties of kaolin one is heavy kaolin and the other is light kaolin. The light kaolin is purer and smaller in particle size than the heavy variety. Only light kaolin is intended for internal use.

Use : as an adsorbent for toxic substances from G.I.T. tract.

Storage: It should be stored in a well-closed container

BISMUTH SUB-CARBONATE

M.F. [(Bio)2 CO3]2 H2O).

Preparation
It involves two steps.

1st Step: Bismuth nitrate is prepared by treating metallic bismuth with nitric acid.
2Bi + 8 HNO3 → 2 Bi(NO3)3 + 2NO + 4H2O

2nd Step: Adding bismuth nitrate solution to a cold sodium carbonate solution with
constant stirring. The white precipitate is washed with water and dried.
4 Bi (NO3)3 + 6 Na2. CO3 + H2O → [(Bio)2 CO3]2 H2O  + 12 NaNO3 + 4CO2

Properties (Physical & Chemical)

White or pale yellowish odourless, tasteless powder, affected by light.

  1. With acids, it produces effervescence.
  2. On heating it yields bimuth oxide (90%)
    [(BiO2) CO3]2 H2O → 2 Bi2 O3 + 2 CO2 + H2O

Assay : Gravimetric method

Weighted sample is ignited to constant weight. It is required to yield not less than 90% of Bismuth oxide.
[(BiO)2 CO3]2 H2O → 2 Bi2 O3 + 2 CO2  + H2O

Use : used in diarrhoea and dysentry.

Storage : It should be stored in well closed air tight container.

SALINE CATHARTICS

These are drugs, when given orally retained in GIT, increases the intestinal bulk by drawing water from circulation by osmosis. They acts as mechanical stimulus, produces increased peristalic movement causing diarrhoea. They are also called as saline purgatives or osmotic laxatives.

SODIUM POTASSIUM TARTRATE

Syn. : Rochelle salt

Preparation

It is obtained by neutralizing a solution of sodium carbonate with potassium bitartrate. The solution is boiled for few mts and then allowed to stand at 60oC for the completion of the reaction. (till the CO2 ceases). The solution is filtered and evaporated.

Properties

Colourless, crystalline efflorescent powder soluble in water, insoluble in alcohol. Upon heating at high temperature gives sodium and potassium carbonates.

2 KNa C4H4O6 + 5O2 → K2CO3 + Na2CO3 + 6 CO2 + 4H2O

Assay: Back titration method

An accurately weighted sample is ignited or heated until carbonized. The residue is boiled with excess of standard sulphuric acid and filtered. Excess of acid is back titrated with standard sodium hydroxide using methyl orange as an indicator

Identification Test :

When heated the salt emits an odour of burning sugar and leaves a residue which is alkaline to litmus paper.

Storage
It should be stored in airtight container

MAGNESIUM SULPHATE

M.F. MgSO4. 7H2O Syn.: Epsom salt.

It can be prepared by alizing sulphuric acid with magnesium oxide or magnesium carbonate or native dolomite

MgO + H2SO4 → MgSO4 + H2O
MgCO3 CaCO3 + 2H2SO4 → MgSO4 + 2H2O + 2CO2 + CaSO4
(Dolomite)

The impurities are precipitated only mag. Sulphate remains in solution. The solution is filtered, and evaporated.

Properties

  1. White powder or colourless crystals, odourless with a bitter taste.
  2. In warm dry air it may lose water by efflorescence.
  3. Freely soluble in water, insoluble in alcohol.

Assay :

By complexometric titration

Weighed amount is dissolved in water, strong ammonia-ammonium chloride buffer is added and titrated against 0.05 m EDTA using Mordant Black II mixture as an indicator. The end point is change of wine red to blue colour.

Use :

  1. Used for constipation.
  2. Evacuation of gall bladder (in case of chole cystitis)

Storage It should be stored in air tight container


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