Granulation effervescent production

With regard to compressibility and compactibility, the considerations pertaining to raw materials in effervescent products are similar to the ones that prevail in evaluating raw materials intended for conventional tablets. However, poor compactibility cannot usually be compensated for by the use of binders, as this will prevent a rapid dissolution of the effervescent tablet. Addition of a binder is generally not as critical for the dissolution of effervescent granules or powders. 

Anhydrous citric acid and NaHCOs were granulated with ethanol in a twin-screw extruder at powder flow rates of 60-90 kg/h in a continuous processJ The air suspension coating-reacting technique also is used in the production of effervescent granulates. 

Citric acid (as either the monohydrate or anhydrous material) is widely used in pharmaceutical formulations and food products, primarily to adjust the pH of solutions. It has also been used experimentally to adjust the pH of tablet matrices in enteric-coated formulations for colon-specific drug delivery. Citric acid monohydrate is used in the preparation of effervescent granules, while anhydrous citric acid is widely used in the preparation of effervescent tablets.Citric acid has also been... 

As an excipient, potassium bicarbonate is generally used in formulations as a source of carbon dioxide in effervescent preparations, at concentrations of 25-50% w/w. It is of particular use in formulations where sodium bicarbonate is unsuitable, for example, when the presence of sodium ions in a formulation needs to be limited or is undesirable. Potassium bicarbonate is often formulated with citric acid or tartaric acid in effervescent tablets or granules on contact with water, carbon dioxide is released through chemical reaction, and the product disintegrates. On occasion, the presence of potassium bicarbonate alone may be sufficient in tablet formulations, as reaction with gastric acid can be sufficient to cause effervescence and product disintegration. 

Tartaric acid is used in beverages, confectionery, food products, and pbarmaceutical formulations as an acidulant. It may also be used as a sequestering agent and as an antioxidant synergist. In pbarmaceutical formulations, it is widely used in combination with bicarbonates, as tbe acid component of effervescent granules, powders, and tablets. 

There are at least theoretical solutions to these two problems. The large volume is less of a problem in dosage forms such as instant or effervescent granules of ibuprofen [505], while the use of large quantities of solvents can sometimes be avoided by using a solvent-free production process such as the roll-mixing process for triturations. 

Effervescent granulation is an important step in the production of fizzy dosage forms that, most of the time, cannot be avoided to achieve the desired characteristics of the effervescent tablets. It is also very critical because it can affect the stability of the final dosage forms. 

All the previous sections provided an overview of all the possible technologies to manufacture effervescent granules but how to choose the most appropriate technique for a certain formulation. An interesting study to figure out the best production method for effervescent tablets was presented by Laugier and Rona (Table 2) (37). 

A number of different types of effervescent granules were once official in the B.P.C. but although most of these have been deleted, products of this type are still very popular. The ingredients of principal therapeutic value are mixed with sodium bicarbonate and both tartaric and citric acids sometimes sucrose is added. 

Sales of Ca supplements alone were 875 million in the United States in 2002, and comprised 60% of all mineral supplement sales (Anonymous, 2004). In 2004, sales of Ca supplements increased by 9.3% (Uhland et ah, 2004), possibly to some extent in response to the Surgeon General s report on bone health that was issued that year. More recently in 2006, it was projected that dietary supplement sales in the United States would approach 5 billion (Anonymous, 2006). While Ca derived from a balanced diet is preferable, Ca supplements are a popular noncaloric alternative for increasing daily Ca intake. There are a vast number of oral Ca supplements available in the market place in the form of capsules, tablets, chewable tablets, effervescent tablets, liquids, powders, suspensions, wafers, and granules. However, not all Ca salts are equally soluble or bioavailable and the dose of Ca on the label of a supplement may not necessarily be reflective of the relative amount of available Ca once consumed. Furthermore, the same Ca salt may be more or less bioavailable depending on the production process and materials used to manufacture the supplement. 

Conventional processing equipment (mixers, granulators, roller compactors, drying equipment, and mills) can be used to produce effervescent preparations if the influence of atmospheric moisture is considered. As a rule, tablet presses have to be adapted to handle effervescent products, except for tablets with a sufficient proportion of a self-lubricating substance, such as acetylsalicylic acid. 

Both chemical and physical properties have to be considered when evaluating effervescent products. In this review, only the physical properties will be discussed, except where the chemical characteristics are especially influenced by the effervescent base. For more detail, Ph. Eur. includes a special disintegration test for effervescent tablets and granules. ... 

Effervescent products are usually packed in individual aluminum foil pouches and effervescent tablets are often packed in metal tubes. To avoid excessive laminate stress, the dimensions of the sachets should be adapted to the dimensions of the tablet or the amount of granulate. These pouches are arranged in conveniently sized strips and stacked in a paperboard box. 

The topogranulator is used extensively to make effervescent products by liquid addition under vacuum or by the Murry fusion method (6). Murry s method uses liberated moisture from the acid in the mix (i.e., hydrous citric acid) to start the acid-base reaction, which generates more water. Thus, granulating of the sodium bicarbonate-citric acid mixture can be accomplished. The water produced must be removed quickly to reproducibly stop the reaction. The topogranultor, because of its ability to compress the particles into the binding moisture, makes a larger, denser... 

Binders for dry granulation, such as lactose, mannitol, dextrose, are almost inappropriate, because they would be effective only in larger amount than that allowed by an effervescent formulations. The binder choice in wet granulation is also limited by the method of production and consequently by the amount of granulating liquid. 

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