Antacids – Pharmaceutical Inorganic Chemistry B. Pharma 1st Semester



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 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:

• 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.

Mechanism of action of antacids:

Compound Chemical


Chemical Reaction
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.

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.

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

(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. 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


• 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

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.

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