Effervescent reactions

A very important property for effervescent products is the adsorption/desorption isotherm of the raw material and, consequently, its moisture content. To avoid a premature effervescent reaction in the tablets. 

The acidity for the effervescent reaction can be obtained from three main sources acids, acid anhydrides, and acid salts. Traditional sources of acid materials are the organic acids, citric and tartaric acid however, some acid salts also are used. 

When granulating with solvents without any moisture, no effervescent reaction will occur provided the raw materials are dry and the process is performed in a low humidity atmosphere. However, citric acid will partly dissolve in ethanol or isopropanol, and function as a binder when the solvent is evaporated. 

When granulating either with solvents containing water or pure water, the effervescent reaction will start. Care must be taken to maintain adequate control of the process. Vacuum processing is often beneficial due to the ability to control the effervescent reaction and the drying process. 

Even the moisture in the air may be enough to initiate the effervescent reaction of an effervescent product if it is not properly protected. When the consumer opens the container, the effervescent product will again be exposed to the moisture in the air. Consequently, the packaging of all effervescent products is very important. The time between tablet production and start of packaging operation should be kept as short as possible. 

Ph. Eur. recommends that effervescent granules and powders be stored in airtight containers. In the past, acidic and alkaline components were wrapped separately to prevent effervescent reactions during the storage of powders and granules. 

In direct compression, the mixing can be performed at normal humidities however, in that case, the mixture is dried (to prevent a premature effervescent reaction) by means of causing dehumidified air to flow through the bed in a suitable container. Tableting and... 

Very hygroscopic. Effervescent reaction with water, producing SiOg. Decomposes on heating at 160-170°C. Forms ethyl acetate... 

When water is used as granulation liquid for effervescents, the effervescent reaction will start and cause a chain reaction. The critical point in such a process is to stop this reaction at the correct time by evaporating the water created by this reaction. In a single-pot processor, this can be very easily and accurately achieved by switching on the vacuum-drying system (possibly supplemented with gas-assisted drying or microwave drying) (24). 

The intrinsic characteristics of effervescent forms bring some considerations that limit the choice of the raw material, including the selection of the active ingredient. Moisture content of the raw material is a very significant aspect, because it affects compressibility and stability of the tablets. To avoid premature effervescent reaction during the process or once the tablets are formed, raw materials with very low moisture content have to be used. 

Because of the nature of the effervescence reaction, additional excipients are sparingly used as the alkaline and acid ingredients also act as fillers to get a tablet bulk. 

It is very soluble in water and very hygroscopic compared to citric acid. In the effervescence reaction with sodium bicarbonate it behaves like citric acid in producing an evident effervescence. It must be used in a higher amount to get the proper stoichiometric proportions, because it is a diprotic acid, while citric acid is a triprotic one. In terms of compressibility it is comparable to citric acid (8). 

It is white in crystalline form and light yellow in fine powder. It is not hygroscopic and this may be helpful in production because it is easier to handle. It is freely soluble in water (1 g in about 3 mL) and absolute ethanol (9). If exposed to light, it gradually darkens. Its behavior in the effervescent reaction with sodium bicarbonate is comparable to the other acids (citric and tartaric) in terms of release rate of carbon dioxide. 

Sodium carbonate is commercially available in three different forms, all very soluble in water anhydrous, monohydrate, or decahydrate (13). It is more resistant to the effervescent reaction and in some formulations can be used as a stabilizing agent in amounts not exceeding the 10% of the batch size. It is used as a stabilizing agent in certain effervescent formulas because it absorbs moisture preferentially, preventing the effervescent reaction from starting. Of course the anhydrous form is the... 

Sodium glycine carbonate provides a light effervescence reaction, but causes rapid disintegration of the tablets, so it has been applied in the preparation of fastdissolving sublingual tablets. It is much more compressible than the other alkaline compounds and has been found suitable for direct compression (17). 

Manufacturing conditions are crucially important even with regards to stability of the products after they have been packed. Almost all the raw materials used for effervescent tablet manufacturing are hygroscopic, and hence moisture absorption from the air must be prevented to avoid the effervescent reaction prior to use of the tablets. 

For this technique, it is necessary to use a granulating liquid that might interact with the powders initiating the effervescent reaction. Hence it is essential to handle the process with great care. 

The peculiar process that distinguishes effervescent granulation consists in a single-step granulation of all the components of the formulation, which can be performed either with nonreactive or reactive liquids with reference to the effervescence reaction. 

The application of microwave radiation, combined with vacuum inside the bowl of the high-shear granulator (27), can also be used to stop the effervescent reaction and to dry the effervescent granules (28). 

I.3.2. Process with Alcohol or Hydroalcoholic Solution. As reported in the previous example, it is sometimes preferable to granulate with a hydroalcoholic solution to initiate a lighter effervescence so as to keep the reaction under better control during the process. Use of alcohols is indispensable in case a binder like PVP is included in the formulation. In fact, the amount of water required to dissolve PVP to obtain the binding action will be too high, and it will not be possible to keep the effervescent reaction under control. 

Effervescence is defined as the evolution of bubbles of gas from a liquid as the result of a chemical reaction. The generation of gas, which is usually carbon dioxide, is usually achieved by spontaneous ehemical reaction between a soluble acid source and an alkali metal carbonate in the presence of water. The reaction can be triggered in the presence of a small amount of water, thus moisture proteetion of sueh oral dosage forms is paramount. This is because effervescence reaction when initiated will proceed spontaneously because one of the by-products is water. 

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