Gastrointestinal Agents

The agents which help in treating the problems related to gastrointestinal tract.

ACIDIFIERS:

A) Acidifying agent

B) Dilute HCl

C) Antacids – Magnesium hydroxide, Sodium bicarbonate, Combination of Antacids.

CATHARTICS:

A) Magnesium sulfate

B) Sodium Orthophosphate

C) Bentonite

PROTECTIVE AND ADSORBENTS :- Used to treat Diarrhoea E.g. Kaolin

• ACIDIFYING AGENTS (ACIDIFIERS) E.g. Dilute HCl

Properties and causes

Those are used to treat “ achlorhydria ” [absence of HCl in stomach ] and Hypochlorhydria ( less HCl in the stomach). Gastric HCl Performs following functions :-

1. It kills the bacteria ingested with food and drinks
2. It soften the food materials
3. It promotes the formation of “ proteolytic enzyme” i.e. pepsin which is formed from pepsinogen when the pH of gastric contents is below 6.  
4. Deficiency of HCl causes gastrointestinal disturbances including mild Diarrhoea, epigastric pain and sensitivity to spicy food.
5. Dil. HCl then further diluted is used as an acidifying agent.

HCl

It is a situation of hydrogen chloride gas in water. Dilute HCl contains 9.5 to 10.5% w/w HCl (at least 9.5g to 10.5g HCl in 100g HCl) NOTE :- Assay is done to check how much compound is present .

It is prepared by diluting conc. HCl when dilute HCl is further diluted with 25-50 volumes of water , it may be used as an “ acidifying agent “.

PREPARATION

1. From sodium chloride (NaCl)

HCl is prepared by treating conc. H₂SO₄ with NaCl.

NaCl + H₂SO₄ ⟶ HCl + NaHSO₄ (sodium hydrogen sulphate)

NaHSO₄ +NaCl  ⟶ HCl + Na₂SO₄

Sodium hydrogen sulphate is reacted further with more quantity of NaCl to obtain more supplies of HCl. The acid so obtained may contain impurities like Sulphuric acid , arsenic acid, chlorine etc. The treatment is done to remove these impurities for E.g. BaCl₂ ( Barium chloride) is used to remove Sulphuric acid by forming BaSO₄ (Barium Sulphate).   

2. By Electrolysis

Hydrogen and Chlorine gases are obtained as bi-products during electrolysis of “sodium chloride”(NaCl ). When manufacturing Caustic soda “ these gases are combined to get HCl gas.

PROPERTIES :

• Physical properties

It is colorless gas, irritating odor, acidic taste, it is very soluble in water.

HCl Solution

It is a clear, colorless, odorless , fuming ,aqueous solution of HCl (gas), which has salty taste. It is strongly acidic to litmus. It’s colour may be yellow due to presence of traces of “ iron and chloride”.

• Chemical Properties

It is a strong acid which turns blue litmus to red , it reacts with metal and their oxides, hydroxide and carbonates to form the chlorides of metals. Mg+ 2HCl ⟶ MgCl₂+H₂↑

Hydroxides HCl + KOH ⟶ KCl + H₂O

Carbonates 2HCl + Na₂CO₃ ⟶ 2NaCl + H₂O + CO₂

With silver nitrate and HCl gives a white precipitate due to formation of silver chloride which is soluble in ammonium hydroxide and insoluble in nitric acid. HCl + AgNO₃ ⟶ AgCl ↓ + HNO₃ (nitric acid)

Utilized for the detection of chloride.

HCL forms dense white fumes with ammonia due to formation of ammonium chloride. HCl+ NH₃ ⟶ NH₄Cl

For Identification purpose also.

USES :

• Used as an acidifying agent
• Used in treatment of achlorhydria

 ANTACIDS

• These are the alkaline basically used to neutralize excess of gastric HCl, which may otherwise cause peptic ulcer and gastritis (inflammation).
• Gastric antacids react with HCl of “gastric contents” to lower the acidity. They inactivate the proteolytic enzyme pepsin.
• Antacids are prescribed by physician for the symptomatic relief of hyper acidity which causes heart burn , uncomfortable feeling from overreacting and a grouping hungry feeling between meals.
• In order for a product to be labelled as antacids according to FDA (Food and Drug association ) it must consist of one or more active ingredients which must contribute at least 25% of the total acid neutralizing capacity of the product.
• Therefore, no more than 4 ingredients can be combined in one formulation.

GOAL OF ANTACID THERAPY

The ultimate goal of therapy is to bring the gastric contents a pH between 3.5 – 5 but is difficult to maintain the desired ph. Antacids tend to increase the activity of secreting gastric cells and their effect as temporary and disappear when medication is discontinued.

                    PROBLEM  FACED DURING ANTACID THERAPY 

• Acid rebound
• Systemic Alkalosis

Such as Na₂CO₃ (Sodium bicarbonate) Which is soluble therefore easily absorbed and produces systematic electrolyte disturbance and symptoms of metabolic alcoholosis.

• Local effect on GASTROINTESTINAL TRACK
• Calcium and Aluminium containing antacids have constipating effect.
• Magnesium containing antacids have laxative actions , so it is quite common to combine constipative and 
  laxative acting antacids in a single preparation.

PREPARATION OF AN IDEAL ANTACIDS

• It should not produce systemic alkalosis
• It should not have laxative or constipative action
• It should exert its effect rapidly which will remain over a long period of time.
• The antacids should buffer in PH 4-6 range
• The reaction of antacid with gastric HCl should not cause large evolution of gas .
• It should exert its effect quickly.

EXAMPLE OF INORGANIC ANTACID

Na :- Na Bicarbonate

Al  :- Al hydroxide gel , Alphosphate

Mg :- Magnesium hydroxide, Mg trisilicate

COMBINATON OF ANTACID PREPARATION

Sodium Bicarbonate :-

(Baking soda)

PREPARATION :

• Na₂CO₃ may be converted into NaHCO₃  by passing CO₂ to saturated aqueous solution

Na₂CO₃ + H₂O + CO₂ ⟶ 2NaHCO₃

• NaHCO₃ can also be prepared by reacting NaCl and ammonium bicarbonate.

NaCl + (NH₄) HCO₃ ⟶ NaHCO₃ + NH₄ Cl

• Physical properties

White crystalline powder, opaque crystals, it is highly soluble in water and practically insoluble in ethyl alcohol because it is highly water soluble so it has very rapid onset of action but relatively short duration.

• Chemical properties- It gradually release Na₂CO₃ on heating in the dry state or in the solution.

2NaHCO₃→Na₂CO₃+CO₂+H₂O+O

• The aqueous solution is alkaline due to litmus due to alkaline.

NaHCO₃+H₂O↔Na⁺ + OH^– + H₂CO₃ But it is slightly alkaline and it fails to turn phenolphthalein red. On the other hand in Na₂CO₃ the carbonate ion is so extensively hydrolyte that the solution is quite alkaline.

• When NaHCO₃is reacted with acid CO₂ is liberated which is not desirable this may cause

NaHCO₃^–+HCl → NaCl+H₂O+CO₂↑

• Assay:- Principle: Acid –Base titration

(Acidimetry)

Titrant :- Standard solution of HCl Indicator :- Methyl orange

    NaHCO₃+HCl → NaCl +H₂O+CO₂↑

Equivalent factor:-

Each ml of 1M HCl= 0.08401gm of NaHCO₃.

Method:- Take accurately weighed amount of sample in conical flask. Dissolve the sample and add few drops of methyl orange as an indicator, titrate this with 1 M HCl till it becomes pink in color.

Uses:- It is used as an antacid and electrolyte replenisher. It is also used in metabolic acid.

ALUMINIUM HYDROXIDE GEL

The other names are:- Aluminium hydroxide suspension or Aluminium hydroxide mixture

DESCRIPTION

Aluminium hydroxide gel is an aqueous suspension of hydrated Aluminium oxide containing different quantities of basic Aluminium carbonate and bicarbonate. It may contain “glycerin” , “sorbitol” , “sucrose” , “saccharin” as sweetening agents and peppermint oil (to impart good flavor) or other suitable flavors. It may also contains suitable antimicrobial agents.

• Aluminium hydroxide gel contains 3.5 to 4.5% (w/w) of Al₂O₃.

PREPARATION

It may be prepared by treating Aluminium chloride and sulphate with ammonia or sodium carbonate.

AlCl₃+3NH₄OH→Al(OH)₃+3NH₄OH

PROPERTIES

It is a white viscous suspension from which small amount of clear liquid may separate on standing.

• In acidic medium it act as a “weak base”.

Al(OH)₃↔Al³⁺ + 3OH^–

• In presence of alkali, it behaves as an acid due to liberation of hydrogen ions.
• Aluminium hydroxide gels are IDEAL BUFFER in the pH 3 to 5 range due to its amphoteric character.
• Gel is tested for its neutralization capacity.

USES

It is used as an antacid, it has constipative effect.

MAGNESIUM  HYDROXIDE

The other names are:- Magnesium hydroxide oral suspension or Magnesium hydroxide mixture or Milk of magnesia or Cream of magnesia.

DESCRIPTION

Mg(OH)₂ is an aqueous  suspension of hydrated magnesium hydroxide. It may be prepared from a suitable grade of light magnesium oxide. It contain 7-8.5 % w/w of hydrated magnesium oxide calculated as magnesium hydroxide.

PROPERTIES

It is available as white uniform suspension, which does not separate easily on standing. It may also be prepared by combining solution of magnesium salt with basic water.

USES

It is used as an antacid, laxative, some magnesium hydroxide products are combine with Aluminium hydroxide to minimize the unwanted laxative effect. Magnesium hydroxide is also a component of antiperspirant preparation.

COMBINATION ANTACID PREPARATION 

Several products are available which contains mixture of antacids.

OBJECTIVES

• To balance  the constipated effect of calcium or Aluminium with the laxative effect of Magnesium
• Rapid onset of action
• Longer duration of actions

EXAMPLES

• Aluminium hydroxide gel with Magnesium hydroxide combination
• Aluminium hydroxide gel and Magnesium Trisilicate combination (Gelsolin)
• Magaldrate which contains Aluminium hydroxide and Magnesium hydroxide . It’s oral suspension and Tablets are available.
• Calcium carbonate containing antacid mixture
• Calcium carbonate can combine with Aluminium hydroxide and Magnesium. E.g. – amphasten
• SIMETHICOME containing antacids.

Defoaming agent

CATHARTICS

Cathartics are also called purgatives. These are used to relieve constipation.

Laxative are mild cathartics.

Following are the types of cathartics.

• STIMULANT
• BULK FORMING
• EMOLLIENT
• SALINE – They work on the osmotic difference. E.g. – MgSO₄ , Sodium orthophosphate and Bentonite

MAGNESIUM SULPHATE

MgSO₄·7H₂O

PREPARATION :- It is prepared by reacting magnesium or it’s oxide or carbonate with dilute sulfuric acid.

Mg + H₂SO4 ⟶ MgSO₄ + H₂↑

MgO + H₂SO₄ ⟶MgSO₄ + H₂O

MgCO₃ + H₂SO₄ ⟶ MgSO₄ + H₂O + CO₂

Dried magnesium sulphate can be obtained by heating at 100 °C and by this method compound looses about 25% of it’s properties.

It is available as colorless crystal or white crystalline powder , odorless bitter and saline taste , very soluble in boiling water , freely soluble in water and insoluble in ethanol.

CHEMICAL PROPERTIES

It efflorescence in warm or dry air. On exposure to day air it looses about 1 mole of water at 70-80 °C it looses 4 moles of water at 100 °C it looses 6 moles of water , at 250 °C it looses all water crystallization. When exposed to moist air , it easily absorbs water.

USES

• It is used as an osmotic laxative.
• It is also used in the treatment of electrolyte dificiency.

BENTONITE

It is a natural colloidal hyderatd aluminium silicate. It is available as very fine powder . It’s composition is mainly

                              AL₂O₃4SiO₂·H₂O

It may also contain calcium , magnesium, iron properties.

It is a pale buff or cream coloured grayish white powder which is free or almost free from gritty particles. It is Hygroscopic (absorbs moisture), ,insoluble in water but swells to approximately 1-12 times it’s volume when added to water, therefore used as thickening agent. It is also a water suspension has pH between 9-10 the particle size of bentonite is about 44um.

One cubic of Bentonite is estimated to contain 9500 billion particles having total surface area more than an acre.

Test is done to find the swelling power of Bentonite

USES

• Used as pharmaceutical aid
• Helps in suspention
• Provides viscosity
• Also has laxative effect

SODIUM ORTHOPHOSPHATE

Na₃PO₄

It is white granular or crystalline solid highly soluble in water producing an alkaline solution it is often partially hydrated and may range from anhydrous Na₃PO₄ for the compound containing 12 H₂O.

          Na₃PO₄·12H₂O (anhydrous form)

PREPARATION

It may be prepared by neutralization of phosphoric acid using sodium hydroxide (NaOH) sodium carbonate (Na₂CO₃).

          H₃PO₄+Na₂CO₃ ⟶ Na₂HPO₄ +CO₂ +H₂O

          Na2HPO₄ + NaOH  ⟶ Na₃PO₄+ H₂O

It may also be produced from calcium phosphate by treating it with Sulphuric acid.