Effervescent Granulation

Effervescent granulation is an important step in the production of fizzy dosage forms that, most of the time, cannot be avoided to achieve the desired characteristics of the effervescent tablets. It is also very critical because it can affect the stability of the final dosage forms. 

The first effervescent preparations were described over two centuries ago in the official compendia they were in powder form for use as cathartic salts. Later, in 1815, a patent described a combination of neutral salt or powder which possesses all the properties of the medicinal spring of Seidlitz in Germany, under the name of Seidlitz Powders, which contains sodium potassium tartarate, sodium bicarbonate, and tartaric acid, in the proportions 3 1 1, respectively (1). Effervescent granules and tablets have become more and more popular as the dosage form because they are readily soluble and easy to consume just by drinking the glass of water where they are dissolved. 

To state the growing interest in such forms, in the 1980s—when electronic bibliography searching was not available yet—the results of a literature search about effervescent forms were published so as to help scientists working on new developments (2). 

According to the 4th edition of the European Pharmacopoeia, the effervescent forms are defined as those granules or tablets that are to be dissolved in water before administration to patients. Effervescent tablets or granules are uncoated and generally contain acidic substances and carbonate or bicarbonate which reacts rapidly to release carbon dioxide when dissolved in water. Disintegration of the tablets usually occurs within 2 min or even less, due to the evolution of carbon dioxide. 

Effervescent forms have many advantages over conventional pharmaceutical forms. They substitute liquid forms when the active ingredient is less stable in liquid form because they can be administered only by first dissolving the tablet in water. Active ingredients that are not stable in liquid form are often more stable in the effervescent form. Their administration is easy and is particularly helpful to patients, for instance, children, who are not able to swallow capsules or tablets. They have a pleasant taste due to carbonation, which helps to mask the bad taste of certain drugs. 

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Bromo-Seltzer Effervescent Granules—sodium bicarbonate, acetaminophen, citric acid, sugar Calcium Rich Rolaids—magnesium hydroxide, calcium carbonate... 

Citrocarbonate Effervescent Granules—sodium bicarbonate, sodium citrate anhydrous Di-Gel Liquid—aluminum hydroxide, simethicone, saccharin, sorbitol, parabens... 

Effervescent granules 325 mg w/2.781 g sodium bicarbonate 2.224 g citric acid/dose measure (ofc) Bromo Se/fzer(Warner-Lambert)... 

Solid dosage form includes capsules, granules, effervescent granules, powders, tablets, insufflations, suppositories (pessaries, bougies and ear cone) etc. 

Effervescent granules It is a mixture of citric and tartaric acids with sodium... 

Antacids Alka-Seltzer Original Effervescent Tablet (568) Alka-Seltzer Extra Strength Effervescent Tablet (588) Alka-Seltzer Gold (309) Alka-Seltzer Heartburn Relief (575) Brioschi (500/6 g dose) Bromo-Seltzer Granules (959/pre-measured packet) Citrocarbonate Effervescent Granules (701/tsp)... 

Vitamin B Complex + Amino Acid + Magnesium Effervescent Granules (Sugar-free)... 

Lindberg, N O., Turfvesson, C., and Olbjer, L. Extrusion of an effervescent granulation with a twin screw extrudeDrug Dev. Ind. Pharm., 13(1987), 1891-1913. 

Robinson, J. McGinity, J. Effervescent Granules and Method for Their Preparation. US Patent 6,488,961, December 3, 2002. 

Effervescent tablets as well as effervescent granules and powders are mentioned in the European Pharmacopoeia (Ph. Eur.), although it does not contain any monographs regarding specific drugs. ... 

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. 

Effervescent granules were prepared in a fluid bed granulator / dryer. 

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 use of binders will normally prevent a rapid dissolution of the effervescent tablet. Therefore, many effervescent tablets are formulated without any binder. However, effervescent granules may be formulated with binders since their large surface area, when compared withthat of the conventional or the effervescent tablet, will result in rapid dissolution. An effervescent... 

Anhydrous citric acid and NaHCOs were granulated with ethanol in a twin-screw extruder at powder flow rates of 60-90 kg/h in a continuous processJ The air suspension coating-reacting technique also is used in the production of effervescent granulates. 

Effervescent granules can be tableted while still damp since moist citric acid acts as a lubricant. The compressed tablets are transferred immediately and continuously to ovens where they are dried. Drying also hardens them. " ... 

For a rapid determination of loss on drying, an IR drying balance may be used. In the matter of size distribution, effervescent granulations are controlled by sieve analysis. 

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. 

Citric acid (as either the monohydrate or anhydrous material) is widely used in pharmaceutical formulations and food products, primarily to adjust the pH of solutions. It has also been used experimentally to adjust the pH of tablet matrices in enteric-coated formulations for colon-specific drug delivery. Citric acid monohydrate is used in the preparation of effervescent granules, while anhydrous citric acid is widely used in the preparation of effervescent tablets.Citric acid has also been... 

GRAS listed. Accepted as a food additive in Europe (the E number E501 refers to potassium carbonates). Included in nonparenteral medicines licensed in the UK and USA (chewable tablets effervescent granules effervescent tablets lozenges oral granules oral suspensions). Included in the Canadian List of Acceptable Non-medicinal Ingredients. 

Tartaric acid is used in beverages, confectionery, food products, and pbarmaceutical formulations as an acidulant. It may also be used as a sequestering agent and as an antioxidant synergist. In pbarmaceutical formulations, it is widely used in combination with bicarbonates, as tbe acid component of effervescent granules, powders, and tablets. 

Vitamins are very often incorporated in effervescent granules. Table 76 gives details of a multivitamin effervescent granule formulation developed in the laboratory. The chemical stability of this guide formulation has not yet been tested. 

There are at least theoretical solutions to these two problems. The large volume is less of a problem in dosage forms such as instant or effervescent granules of ibuprofen [505], while the use of large quantities of solvents can sometimes be avoided by using a solvent-free production process such as the roll-mixing process for triturations. 

Multivitamin Effervescent Granules Multivitamin Effervescent Tablets... 

Paracetamol (= Acetaminophen) + Doxylamine + Caffeine Effervescent Granules... 

Magnesium Effervescent Granules Vitamin B Complex + Carnitine Tablet... 

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