Effervescent products

Organic acids Citric acid Aspergillus niger Effervescent products sodium citrate used as an anticoagulant potassium citrate used to treat cystitis... 

However, these reactions do not always occur. In some instances there may be steric factors in the API molecule that restrict access to the reactive group and the reaction does not occur, or occurs at a much-reduced rate. For almost all chemical interactions, a key component is presence of free (unbound) water (23,24). In the absence of a sufficient amount of free water, the reactions do not proceed. This is the basis for using very low humidity manufacturing and packaging facilities for the manufacture of effervescent products. The free water layer serves to dissolve sufficient of the drug and the excipient, or to form bridges between particles, such that the components/reactants come into sufficiently close contact for the reaction to occur. 

Effervescent products should be stored in tightly closed containers. Desiccants are usually added to the containers. 

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. 

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. 

Other acids Malic acid is hygroscopic and readily soluble in water. It has been suggested for effervescent products. ... 

Many drugs and drug compositions have been used for effervescent products. Some of these are listed below. 

Acetylsalicylic acid (aspirin) is a common drug in many different effervescent products. ... 

Effervescent products of water-insoluble drugs have been manufactured. A successful example is the effervescent activated charcoal preparation suggested in the management of theophylline poisoning. ... 

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. 

Some effervescent tablet products are successfully produced by direct compression (e.g., acetylsalicylic acid products). Direct compression normally requires careful selection of raw materials to achieve a free-flowing, non-segregating, compressible mixture. Effervescent products present the same problems as conventional products in direct compression. 

A perfect lubricant (or auxiliary agent, in general) for effervescent products must be non-toxic, tasteless, and water-soluble. Very few traditional lubricants fulfill these requirements. 

Sodium stearate and sodium oleate are water-soluble in low concentrations. They have the characteristic soapy taste, which virtually precludes their use in effervescent products. 

Effervescent products generally do not require diluents. The effervescent materials themselves will have to be added in large quantities. 

Sucrose and other natural sweeteners, such as sorbitol, can be used in effervescent products, although artificial sweetening agents are customary. However, the application of artificial sweeteners is restricted by health regulations. Therefore, the use of such sweeteners will vary from one country to the next based on national standards. 

To reduce the formation of foam, and consequently the tendency of drugs to stick to the wall of the glass above the water level, an antifoaming agent, such as poly-dimethylsiloxane, can be used. However, antifoaming agents do not normally form constituents of effervescent products. 

Literature on formulations of effervescent products it relatively sparse. Table 1 presents some examples of effervescent products on the Nordic market. 

The greatest problem with effervescent products is the loss of reactivity with time if exposed prematurely to moisture (i.e., the stability of the effervescent system). In addition, the stability of the drug and some excipients, such as flavors, also must be considered. 

Effervescent products are not stable in the presence of moisture. Most effervescent products are hygroscopic and can therefore adsorb enough moisture to initiate degradation if they are not suitably packaged. 

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. ... 

Near IR (NIR) is a quick and non-destructive method for the determination of water in effervescent products. In addition, it is suitable for in-process quality control. Measurement of pH of the solution is often performed. The conditions are important for congruent results. 

The disintegration and dissolution times are very important characteristics of effervescent products. A well-formulated effervescent tablet will disintegrate and dissolve within 1-2 min to form a clear solution. Consequently, the residue of undissolved drug must be minimal. The temperature of the water influences the dissolution time. It is, therefore, important to choose a water temperature that is actually used by consumers (e.g., cold tap water). Ph. Eur. includes a general requirement on disintegration time of 5 min in water 15-25°C.t ... 

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. 

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 traditional effervescent product is dissolved prior to oral intake. This requires the drug to have an acceptable taste. Since the drug is given as a solution, the absorption is normally rapid and the bioavailability is usually good. 

The commercial manufacturing of effervescent products involves controlling air humidity in the production area. Special tablet machines are generally required, and the package is a very important part of the effervescent product. Over-the-counter analgesics have been very successful as effervescent tablets on certain markets. 

Murray, R.B. New approach to the fusion method for preparing granular effervescent products. J. Pharm. Sci. 1968, 57, 1776-1779. 

Chemical stability, disintegration rate, dissolution profile, friability, and hardness are the major stability attributes for the tablet dosage form. An unoptimized tablet formulation may become soft or very hard after storage, with altered dissolution profiles, and as a result, its dissolution profile and bioavailability may not be appropriate. If effervescent products are not properly formulated, manufactured, and packaged, the premature acid-base reaction will cause the product s self-destruction. 

Spray-dried particles have also been incorporated into effervescent products. In one study, spray drying was used to protect a degradation-sensitive active by coating fine particles of the drug with a sugar alcohol solution (50). In vivo results of tablets made using the spray-dried particles combined with coated citric add and sodium bicarbonate revealed that the active was rapidly absorbed from the tablet. 

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... 

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