Effervescent Dosage Manufacturing

Effervescent tablets are an interesting pharmaceutical dosage form, offering some unique advantages when compared with simple tablets. However, the manufacturing process involves some critical steps that need to be addressed carefully during formulation and factory design.
Apr 01, 2003
Volume 15, Issue 4

Oral dosage forms are the most popular way of taking medication, despite having some disadvantages compared with other methods. One such disadvantage is the risk of slow absorption of the active pharmaceutical ingredient (API), which can be overcome by administering the drug in liquid form and, therefore, possibly allowing the use of a lower dosage. However, because many APIs only show a limited level of stability in liquid form, effervescent tablets, which are dissolved in water before administration, have been formulated as an alternative dosage form.

Advantages of effervescent tablets compared with other oral dosage forms include:

  • an opportunity for formulators to improve the taste;
  • a more gentle action on a patient's stomach;
  • marketing aspects (fizzy tablets may have more consumer appeal than traditional dosage forms).

Citric acid and sodium bicarbonate
The disadvantages of effervescent dosage forms are the need for larger tablets, a complex production process and, very often, the need for specialist packaging materials.

Fundamentals of effervescents Effervescents consist of a soluble organic acid and an alkali metal carbonate salt, one of which is often the API. Carbon dioxide is formed if this mixture comes into contact with water. Typical examples of the acids and alkalis used include:

  • citric acid
  • tartaric acid
  • malic acid
  • fumaric acid
  • adipic acid
  • sodium bicarbonate
  • sodium carbonate
  • sodium sesquicarbonate
  • potassium bicarbonate
  • potassium carbonate

See sidebar "Citric acid and sodium bicarbonate" for an example.

Figure 1: Example of closed powder handling using IBCs, docking stations and split valve technology (courtesy of Gallay Systems Ltd, UK).
Production Producing effervescent tablets requires a conventional solid dosage form manufacturing process that has been adapted to include additional features because of the unique characteristics of the product.

Material handling. The primary material used in the manufacture of effervescents is relatively hygroscopic, that is, it absorbs moisture from the air. However, this must be prevented because it will initiate the effervescent reaction. One of the principle strategies used to overcome this problem is a completely closed material handling system, which includes intermediate bulk containers (IBCs), docking stations and split valve technology (Figure 1). In addition, the ventilating air must contain a sufficiently low moisture content. This method is particularly useful if potent actives are handled that require a high level of operator protection. The alternative is the open handling of a product, which allows the use of standard equipment - although the ventilating air must still contain minimum moisture levels.

Granulation and drying Because most tablets are compressed by high speed rotary tablet presses, the material fed into the presses has to have properties that prevent segregation and ensure homogeneous filling of the dies, to produce tablets of equal weight. The most common approach to achieving materials with these characteristics is to granulate the raw materials. Because wet granulation will initiate the effervescent reaction, several alternatives have been established.

Dry methods. Dry methods, such as slugging, direct compression and roller compaction are regularly used to produce solid dosage forms.2 These are the preferred methods of producing effervescents because no liquid is involved, which means that no additional drying step is required. Another advantage is the reduced need for equipment because of the limited number of unit operations required and, as a consequence, ventilation of the machinery and/or the facility can be simplified.

Indeed, the roller compaction method, if properly automated, can lead to very high throughput. However, the main argument against the use of dry methods is the need for expensive excipients.

Wet granulation. For the wet granulation process, two separate granulation steps are run (one each for the alkaline and the acid components) with a subsequent dry blending step. This can be done in a high shear granulator (with subsequent drying), a single pot or in a fluid bed spray granulator.2 The advantage of this method is that only conventional equipment is needed, which could also be used for granulating and drying other materials. The major disadvantages are the running time required and the cleaning, particularly if two parallel lines are not available for the two granulations. The blending process can be a critical step and may affect the homogeneity of the tablets because not all the materials are bonded into one granule as in a conventional wet granulation process.

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