A Review on Effervescent Granules

Effervescent granules are among the most commonly used granular dosage forms for oral administration. These formulations typically consist of an effervescent base, comprising sodium bicarbonates, citric acid, and tartaric acid.(1) Effervescent granules are extensively employed in pharmaceutical products, including analgesics, antacids, and cough formulations.(2) These granules are highly soluble, stable, and exhibit rapid disintegration upon contact with water, making them a convenient and patient-friendly dosage form.(3) upon addition to water, the granules rapidly dissolve, releasing carbon dioxide as a result of the acid-base reaction between the acidic components (citric acid) and the basic component (sodium bicarbonate). The effervescence not only enhances the dispersion of granules but also improves the dissolution rate of the active pharmaceutical ingredient (api). Additionally, the release of co? contributes to improved taste masking, which in turn enhances patient compliance. The basic reaction in effervescent systems can be depicted as follows: 3NaHCO3 (aq) + H3C6H5O7 (aq) → 3H2O (aq) + 3CO2 + Na3CH5O7 (aq) (sodium bicarbonate + citric acid → water + carbon dioxide + sodium citrate) Mechanism of effervescent granules.

The process of effervescent granules involves a chemical reaction between acid and base components, facilitated by the presence of water. This reaction results in the release of carbon dioxide, which promotes the rapid breakdown of granules and the dispersion of the drug.

1. Wetting and starting: When the granules come into contact with water, the surface becomes wet, resulting in the dissolution of. The acidic component, such as citric acid, and the basic component, like sodium bicarbonate, are present in the mixture.
2. Acid-base reaction: When an acid and a base react, they form a salt, water, and carbon dioxide gas. 3NaHCO3 + H3C6H5O7 → Na3CH5O7 + 3H2O + 3CO2. (sodium bicarbonate + citric acid → sodium citrate + water + carbon dioxide)
3. CO2 evolution and disintegration: The generation of co2 produces a bubbly effect, causing the granules to break down into tiny particles. This helps ensure that the active pharmaceutical ingredient (API) is evenly distributed in the solution.
4. Improved solubility and absorption. The presence of effervescence improves the solubility and dissolution rate of apis, especially those with low water solubility. Furthermore, the bubbly action conceals unpleasant tastes, thereby enhancing patient compliance.
5. Outcome: The process leads to a uniform and enjoyable drink, with enhanced accessibility and convenience compared to traditional solid forms of medication.(4,5)

Fig No.1 Mechanism of Effervescent Granules

Fundamentals of Effervescent:

Effervescence is a result of a soluble organic acid and an alkali metal carbonate salt, with the latter often being the api. When CO2 comes into contact with water, it is released. The necessary components for effervescent granules are acid and base, along with a sweetener and a binding agent.

• Acids: Samples of such acids include Citric acid, Tartaric acid, Malic acid, Adipic acid and Fumaric acid.
• Bases: Samples of bases include Sodium carbonate, Sodium hydrogen carbonate, Potassium bicarbonate, Sodium sesquicarbonate.
• Sweetener: Mannitol, Sucrose.
• Binding Agent: Starch paste
• Vehicle: Ethanol (non aqueous method).(6)

ADVANTAGES :

1. Easy to administer for patients
2. Quick Onset of action.
3. It also mask unpleasant taste.
4. More stable than liquid dosage form. (7)

DISADVANTAGES :

1. It is not recommended for children to consume this product due to the potential toxicity of carbon dioxide gas.
2. If the packaging is not done correctly, there is a possibility of physical deterioration.
3. It has shorter shelf life compared to the other dosage form.(8)

PACKAGING OF EFFERVESCENT GRANULES

1. Effervescent packaging on market,
2. Primary packaging: blisters, bottles, tubes, sachets, and stick packs;
3. Secondary packaging: paperboard cartons, side sealed bags, and wallet packs;
4. Product type: tablets, powders, granules;
5. Material type: plastic [PE, PP, PVC], aluminium, metal . (9)

FORMULATION METHODS:

There are different ways to prepare effervescent granules, such as mixing them with water or adding them to a liquid. The wet method, hot melt extrusion technique, dry method, and non-aqueous method are the different techniques used in the production of plastic film.

1. Wet method : It is the most ancient technique of grain refinement. Initially, all the ingredients are ground into a fine powder and then passed through a sieve to ensure consistent particle size. Wet massing is the most crucial step in the wet granulation process. During this stage of the process, a granulating agent is incorporated into the powdered mixture. Once the powdered mixture is adequately dampened, it is then passed through a fine mesh screen to achieve the desired particle size. After the granules are formed, they are dried using a hot air oven. (10)

 2. Hot melt extrusion technique : Firstly weigh the required quantity of ingredients and pass them through sieve no 18.Heat it a temperature of about 50o c to 80o c until a molten mass is obtained. Allow the mass to cool down to room temperature and then pass it through either sieve no8 or sieve no10 to obtain granules. Finally, dry the granules at a temperature not exceeding 60°C. (11)

3. Dry method : It is the primary method for the preparation of effervescent granules. This fusion method eliminates the compression step. In this technique, the powders are heated using an oven or another heat source. The fusion technique utilizes the water of crystallization found in citric acids as a binding agent. The powdered mixture is thoroughly mixed to ensure a consistent mass and is then sieved to obtain granules. Finally, the granules are dried in an oven. (12)

 4. Non aqueous method : The ingredients are measured and are placed into a porcelain dish. To the ingredients, gradually incorporate ethanol drop by drop until it solidifies into a mold. Pass the mould through the sieve no 10, granules are obtained & these granules are kept in an oven at an temperature of 55o c for 1-2 hrs, the granules are again passed through the sieve to obtain uniform sized granules.These granules are further packed in sachets and are stored for further use. (13)

EVALUATION OF EFFERVESCENT GRANULES

Angle of Repose

The angle at which effervescent granules tend to settle, known as the angle of repose, typically falls between 25° and 40°, with variations depending on factors such as the formulation, particle size, moisture content, and surface texture of the granules. If there is moisture or the granules are sticky, the angle of repose will rise, indicating a decrease in the flowability of the material.

tan θ = h/r

θ = tan¹ (h/r)

Where:

θ = angle of repose (in degrees) h = height of the granule pile

r = radius of the base of the pile.

Table No 2 : Angle of repose with its flow nature