The manufacture of effervescent tablets is similar in many ways to that of conventional granules or tablets, although due to the hygroscopicity and potential onset of the effervescence reaction in the presence of water, environmental control of relative humidity and water levels is of major importance during manufacture.
A maximum of 25 % relative humidity or less is sufficient to avoid problems of atmospheric moisture. Moderate to cool temperatures (25 ºC) in the manufacturing areas are also essential to prevent the granulations or tablets from sticking to the machinery and from picking up moisture from the air, which may cause product instability.
Effervescent tablets are manufactured by both direct compression method and by compaction via granulation. In the latter case, traditional wet granulation is seldom used; instead, granules are formed by the fusion of particles as a result of their partial dissolution during wet massing of a moistened powder.
The equipment used in the manufacture of effervescent tablets are also the same as that for conventional tablets; the only difference is that it uses the rotatory press with special adaptations for compression.
In-process quality control is of major importance for these formulations as are stability testing and stress testing of packaging. Tablet disintegration and dissolution are of prime importance, and disintegration should be carried out using representative conditions. Hardness and friability are also important as these large tablets tend to chip easily. Common areas for problems are that the packaging permits entry of water, the seal is compromised or that the excipients can react with each other.
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This is basically the same as for conventional tablets. In this technique, the acid and bicarbonate components can be granulated either separately or as a mixture with ethanol, ethanol-water mixture, isopropanol, etc.
Usually, water is not used because of product instability in water. Citric acid which normally dissolves in ethanol or isopropanol serves as a binder when the solvent is evaporated. However, wet granulation of the effervescent base can be performed by carefully adding 0.1 to 1.0 percent water (weight-to-weight basis) to a blend of raw materials that possess the uniformity, compressibility, and flowability needed to produce good-quality tablets, but which lacks the needed binding properties.
The free water which is usually added in the form of a fine spray to selected formulation components while mixing in a suitable blender acts as a binder. The granulation steps must be precisely timed and the ingredients mixed thoroughly to distribute the granulating fluid evenly in the blend. The mix is then quickly discharged to drying ovens.
Because variations in drying times and temperatures can affect the finished product, operational parameters of all equipment, especially drying equipment, must be constantly monitored. While stable granulations will ultimately be made, differences in tablet hardness and disintegration times may result from either over- or under-reacting the granulation.
After drying, the granules are sized, and a final mix is performed. The granules are then compressed into tablets using tablet machines that can deliver high compression forces.
If the tablets are to be wrapped in foil or placed into a tube, careful attention needs to be given to the tablet parameters during compression. Also, the tablet thickness needs to be monitored to ensure the wrapping or packaging equipment can handle the tablets.
In this method, the effervescent mixture is heated up to 100 °C so that the water of crystallization or hydration from the hydrated citric acid is released, after which it is moistened with ethanol and added to the sodium bicarbonate. Partial fusion occurs and granules are formed by kneading in a suitable mixer.
The granules are tableted while still damp with the moist citric acid acting as a lubricant. The compressed tablets are transferred immediately to ovens where they are dried continuously at 70 – 75 °C.
The tablets harden on drying and are packed in aluminum foil lined with polyethylene.
Manufacture of effervescent tablets using dry granulation method can be accomplished with the use of special processing equipment known as a “roller compactor” or “chilsonator”. These machines compress premixed powders between two counter-rotating rollers under extreme pressure.
Depending on the configuration of the roller, the feed material may be compacted into dense ribbon-like materials known as flakes (smooth rolls) or dense briquettes (almond or stick-shaped) if the rollers have grooved or etched surfaces. The compressed material is reduced to the proper size for tablet granulation purposes.
Another dry granulation procedure is slugging, in which the powder particles are compressed into large flat tablets or pellets using a tablet press or more usually, a heavy-duty tablet-compacting equipment. The resulting tablets or slug are milled to yield the desired granule characteristics.
Both of these processes are used for materials that ordinarily will not compress using the more conventional wet granulation techniques and require precompression to increase density or exclude entrapped air due to porosity.
In this method, effervescent tablets are compressed directly from powder blends of the active ingredient and suitable excipients (including the acid and alkali components) without an intermediate granulating step.
Direct compression normally requires careful selection of raw materials to achieve a free-flowing, non-segregating, compressible powder blend.
Measurements have been made of the mechanical properties of effervescent raw materials and mixtures to predict compressibility when directly compressed.
Fumaric acid had the best compression properties among the acids tested, while sodium bicarbonate was the best among the carbonates. Acetylsalicylic acid and ascorbic acid effervescent tablets are typical examples of effervescent tablets produced by the direct compression method.