Friday, July 23, 2021

Formulation, Manufacture and Evaluation of Effervescent Tablets

by | November 10, 2020 4

Effervescent tablets are uncoated tablet preparations containing mixtures of medicinal agents with acid substances and carbonates or hydrogen carbonates, which react rapidly in the presence of water to release carbon dioxide. They are solid dosage forms which are intended to be dissolved or dispersed in a glass of water before administration.

Effervescent tablets have specific characteristics that allow rapid adsorption and dissolution of the intended drug. The availability of dosage forms based on effervescence technology gained much importance with the technology of Alka-Seltzer in the 1930s. The widespread use of effervescent tablets has been achieved as a result of their convenience and also the ease in which they can be consumed.

This article reviews the fundamentals of effervescent tablets, effervescence reaction, excipients used in effervescent tablets, production techniques, quality control tests as well as the advantages and disadvantages of effervescent tablets.

Effervescence reaction

3NaHCO3 (aq) + H3C6H5O7 (aq) →  3H2O (aq) + 3CO2 (g)+ 3Na3C6H5O7 (aq)

Effervescence reaction equation

Effervescence is the evolution of bubbles of gas (carbon dioxide) from a liquid as the result of a chemical reaction between acids and bases. The reaction proceeds spontaneously when the acid and carbonate components are mixed in water, even with a very small amount as a catalyzing agent. Because water is one of the reaction products, it will accelerate the rate of reaction, leading to difficulty in stopping the reaction.

Drugs formulated as effervescent tablets

Drugs formulated as effervescent dosage forms include:

a. Those that are difficult to digest or disruptive to the stomach

A classic example is calcium carbonate, the most widely used form of calcium. In a normal tablet or powder, the calcium carbonate dissolves in the stomach acid and is carried into the digestive system for absorption. As the calcium carbonate dissolves, however, it releases carbon dioxide, resulting in stomach gas. On the other hand, as people age, they have less acid in the stomach and thus a calcium carbonate tablet may pass through the stomach without dissolving. That, in turn, may lead to constipation. However, if the calcium carbonate is taken in an effervescent formulation, the calcium dissolves in water and is readily available for the body to absorb without the risk of excessive gas in the stomach or of constipation.

b. Those that are pH-sensitive

The low pH in the stomach can cause active ingredients (e.g., amino acids and antibiotics) to become denatured, lose activity, or cause them to remain inactive. Effervescent ingredients, however, can buffer the water-active solution so that the stomach pH increases (becomes less acidic) and thus prevent the degradation or inactivation of the active ingredient. This buffering effect (via carbonation) induces rapid emptying of the stomach (usually within 20 minutes) and the residence time of the drug in the stomach will thus be short. The result is maximum absorption of the active ingredient.

c. Those requiring a large dose

Drugs requiring large dose can be formulated as effervescent tablets. A typical effervescent tablet (1 inch in diameter, weighing 5 grams in total weight) can include more than 2,000 milligrams of water-soluble active ingredients in a single dose. If the required dose is larger than that, the powder form is a common means of delivery.

d. Those that are susceptible to light, oxygen, or moisture

Many vitamins fall into this category. Typical effervescent formulations have less than 0.5 per cent of free moisture. To maintain that level and prevent other damage from the ambient environment, the formulation’s package should be 0.001-inch-thick aluminium that completely blocks light, oxygen, and moisture.

Constituents of effervescent tablets/ Excipients used in the manufacture of effervescent tablets

In addition to active ingredients, effervescent tablets contain:

1. Acid Components

a. Citric acid

Citric acid is an odourless, colourless, translucent crystal with a strong acidic taste. It is the most commonly used acid component, being readily abundant and relatively inexpensive. Citric acid imparts a citrus-like taste to the product. It is very soluble in water and freely soluble in ethanol.

Citric acid is commercially available in fine granular, free-flowing, anhydrous, and monohydrate food-grade forms. It is very hygroscopic. Special care must be taken to prevent its exposure to and storage in high-humidity areas especially if it is removed from its original container and not suitably repackaged.

b. Tartaric acid

This is an odourless, colourless, monoclinic crystal or a white (almost white) crystalline powder with an extremely tart taste. It is used in many effervescent preparations, being readily available commercially.

Tartaric acid is more soluble than citric acid. It is soluble in less than 1 part of water and 1 in 2.5 of ethanol. It is as strong an acid as citric acid, but more must be used to achieve equivalent acid concentration since it is diprotic, whereas citric acid is triprotic. Tartaric acid is deliquescent at relative humidity of above 75%.

c. Ascorbic acid

This is a colourless or white to yellow coloured, non-hygroscopic, odourless, crystalline powder with a sharp acidic taste. It is freely soluble in water and ethanol but darkens on exposure to light. It is less hygroscopic than citric or tartaric acid.

d. Malic acid

Malic acid is a white or nearly white, crystalline powder or granule having a slight odour and a strongly acidic taste. It is hygroscopic and readily soluble. Although its acid strength is less than that of citric or tartaric acid, malic acid provides sufficient effervescence when combined with a carbonate source. Malic acid also has a smooth, tart taste that does not “burst” in flavour as does the tart taste of citric acid.

e. Other sources of acid components

Other sources of acid components used in the manufacture of effervescent tablets include fumaric acid, nicotinic acid, acetylsalicylic acid, succinic and adipic acids, acid anhydrides (e.g., glutaric anhydride, succinic anhydride, etc.) and acid salts (e.g., amino acid hydrochlorides, sodium dihydrogen phosphate, acid citrate salts, etc.).

2. Alkali Components

a. Sodium bicarbonate

This is the most widely used alkali source in effervescent products. It is a white, odourless, crystalline powder with a saline, slightly alkaline taste. Sodium bicarbonate has low moisture content (1 % at 80 % relative humidity), yields about 52 % carbon dioxide by weight and is soluble in water (1 in 11 parts at 20 °C) but insoluble in 96 % ethanol at 20 °C.

Sodium bicarbonate produces a clear solution after tablet disintegration and forms carbonate when treated with heat. It is commercially available in five particle size grades ranging from a fine powder to a free-flowing uniform granule.

b. Other sources of alkali components

Other sources of alkali components include sodium carbonate (soda ash) and sodium glycine carbonate. When sodium ion is undesirable or needs to be limited, as in the case of antacid products, in which the dosage is dependent on the amount of sodium recommended for ingestion. Other sources of alkali that can be used include potassium bicarbonate, potassium carbonate and calcium carbonate.

3. Binders

Binders are normally necessary in effervescent tablets to bring the tablets’ hardness to a point where handling is possible. These binders should be water-soluble. A binder should be used very cautiously because it can carry free moisture into the tablet, which is undesirable and can increase the disintegration time when used in large quantities. The ideal amount of binder is one that makes the tablet hard enough to handle but soft enough to disintegrate and dry enough to be stable. PEG 6000 at 3 % use level can be used as a dry binder. However, most effervescent products are formulated without a binder because of its disadvantage of carrying free moisture into the tablets.

4. Lubricants

Of all the excipients compounded into effervescent tablets, the lubricant is one of the most important because, without this material, production of effervescent tablets on high-speed equipment would not be possible. Lubrication of effervescent granulation has historically been the main stumbling block to an acceptable, marketable product partly due to the nature of the raw materials used and partly due to the rapid tablet disintegration usually required. Many substances are effective lubricants in certain concentrations but inhibit tablet disintegration at these same concentrations. When the concentration is lowered to permit proper disintegration of the tablet, the lubricating efficiency of these materials are lost or so greatly diminished that they are no longer useful.

A perfect lubricant (or auxiliary agent, in general) for effervescent products must be water-soluble, non-toxic and tasteless. Typical lubricants such as magnesium stearate and stearic acid are of limited use due to their insolubility in water and thus, they tend to float on the surface, creating an unattractive “oil slick”.  This can sometimes be remedied by adding emulsifiers such as lecithin or dioctyl sodium sulfosuccinate. Most formulators have to use water-soluble lubricants such as sodium benzoate, polyethylene glycol, and adipic acid. These are minimally effective and depend heavily on the granulation method used. Sodium chloride, sodium acetate, and D, L-leucine (water-soluble lubricants) have also been suggested for effervescent tablets lubrication.

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Comments4

  1. Basil Alzabin says:

    Very beneficial hopefully more information and knowledge

  2. adriaan says:

    I did enjoy reading this and learning about effervescent tablets.
    Great work, thank you.

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