Effervescent excipients

The other class of reservoir-type pulsatile systems is based on rupturable coatings in contrast to the swella-ble/erodible layers of the previous section. The drug is released from a core (tablet or capsule) after rupturing of a surrormding polymer layer, caused by a pressure build-up within the system. The pressure necessary to rupture the coating can be achieved with gas-producing effervescent excipients, an increased inner osmotic... 

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. 

Effervescents comprise a soluble organic acid and an alkali metal carbonate salt. Citric acid is most commonly used for its flavor-enhancing properties. Malic acid imparts a smoother after taste and fumaric, ascorbic, adipic, and tartaric acids are less commonly used [14], Sodium bicarbonate is the most common alkali, but potassium bicarbonate can be used if sodium levels are a potential issue with the formulation. Both sodium and potassium carbonate can also be employed. Other excipients include water-soluble binders such as dextrose or lactose, and binder levels are kept to a minimum to avoid retardation of disintegration. All ingredients must be anhydrous to prevent the components within the formulation reacting with each other during storage. 

Available as anhydrous and monohydrate anhydrous material used for direct compression due to superior compressibility Originally direct-compression excipient, now often included in granulations due to its excellent compressibihty Direct-compression diluent, often used in chewable tablets Was widely used as sweetener/filler in effervescent tablets and chewable tablets less popular nowadays due to cariogenicity Versatile material that can be used as diluent binder, and disintegtant Brittle material... 

The drug can be mixed with the effervescent granulate and other excipients or be a part of the granulation. When mixing low proportions of drug with granulate, the risk of segregation must be taken into account. 

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. 

Excipients such as mannitol can affect small intestinal transit, which in turn can affect the absorption of certain drugs. Oral solutions are rarely likely to fall short of bioequivalence relative to solid oral formulations, although during the development of a ranitidine effervescent oral solution dosage form containing sodium acid pyrophosphate (SAPP), a marked decrease in absorption was observed in the extent of ranitidine absorption from the liquid formulation relative to the conventional oral tablet. The formulation contained 150 mg ranitidine with 1132 mg SAPP together with 1.5 MBq hndium chloride solutions. Small intestinal transit time was decreased to 56% in the presence of the excipient. The rapid small intestinal transit associated with an excipient of a solution dosage form resulted in a decreased extent of ranitidine absorption. " ... 

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. 

Since an effervescent tablet is required to dissolve within 2 min or less in a glass of water (about 100 mL), the solubility of raw materials and their rate of solubility are other significant parameters. The active ingredient must be soluble, water dispersible, or at least solubilized by salt formation during the dissolution in the glass of water. The rest of the excipients, such as additives like sweeteners, coloring agents, flavors, also have to be water soluble. 

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. 

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