Effervescent Forms

Manufacturing conditions are crucially important even with regards to stability of the products after they have been packed. Almost all the raw materials used for effervescent tablet manufacturing are hygroscopic, and hence moisture absorption from the air must be prevented to avoid the effervescent reaction prior to use of the tablets. 

In this case only the packaging area will be ventilated with low moisture content of air. Otherwise traditional open handling systems can be employed but the whole facility has to be conditioned with air at minimum level of moisture content 

Certain tablets are also wrapped in an aluminum foil before packaging in the tube and this seems to be the best solution for long-term stability. Patented types of tubes containing silica-gel in the internal side of the cap are the most recent invention (25). 

For tablets that are packed in strips, it is essential that the packaging machine has a fine control over the temperature of the welding unit, so that an accurate sealing of the strips can be obtained and overheating phenomenon that could provoke release of residual water from the tablets can be avoided (24). 

Two main granulation methods have been known for a long time. The 1911 edition of the British Pharmacopoeia reported a detailed description of the manufacturing 

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Acetylsalicylic acid (aspirin) Although acetyl-salicylic acid is a drug frequently used in effervescent form, it cannot be used as the acid source because of its low water solubility. Additional acid is necessary to decrease the reaction time. 

A. Abebe, D. Chulia, J. P. Richer, M. Tendero, A. Verain, and P. Ozil, Formulation methodology application to an effervescent form, Proc. 5th Internat. Conf. Pharm. Tech., APGI (1989). 

White crystals very hygroscopic and reactive reacts with water with vigorous effervescence forms a blue-white mist in moist air. 

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. 

The intrinsic characteristics of effervescent forms bring some considerations that limit the choice of the raw material, including the selection of the active ingredient. Moisture content of the raw material is a very significant aspect, because it affects compressibility and stability of the tablets. To avoid premature effervescent reaction during the process or once the tablets are formed, raw materials with very low moisture content have to be used. 

In the latest development in effervescent forms, some formulations have been designed to control the rate of effervescence, so to obtain a rapid, intermediate, or slow rate. The rate control is strictly related to the acid-alkaline components ratio, but the chemical properties of the effervescent exdpients or their combinations can have influence on it, especially when a slow rate of effervescence is required. 

Sodium bicarbonate is the major source of carbon dioxide in effervescent forms and is able to provide a yield of 52% of carbon dioxide. It is commerdally available in five grades according to particle size, from free-flowing uniform granule to fine powder, which are odorless and slightly alkaline in taste. When heated, the bicarbonate is converted into anhydrous sodium carbonate. This reaction is time and temperature dependent. Ninety percent of the conversion is achieved within 75 min at 93°C, but dehydration starts at 50°C, which must be considered as a critical temperature in processing (12). 

In a 250 ml. conical flask, fitted with an air condenser of wide bore, place 50 g. (51 -5 ml.) of acetonylacetone (see Section V,9, Note 2) and 100 g. of ammonium carbonate (lump form). Heat the mixture in an oil bath at 100° until effervescence stops (60-90 minutes) some ammonium carbonate (or carbamate) sublimes into the condenser and this must be pushed back into the reaction mixture by means of a stout glass rod. Replace the air condenser by a Liebig s condenser with wide bore inner tube and reflux the mixture gently (bath temperature, 115°) for a further 30 minutes dissolve the solid which has sublimed into the condenser in about 5 ml. of hot water and return the solution to the reaction mixture. 

Amino-2-hydroxybenZOiC acid. This derivative (18) more commonly known as 4-aminosa1icy1ic acid, forms white crystals from ethanol, melts with effervescence and darkens on exposure to light and air. A reddish-brown crystalline powder is obtained on recrystallization from ethanol —diethyl ether. The compound is soluble ia dilute solutioas of nitric acid and sodium hydroxide, ethanol, and acetone slightly soluble in water and diethyl ether and virtually insoluble in benzene, chloroform or carbon tetrachloride. It is unstable in aqueous solution and decarboxylates to form 3-amiaophenol. Because of the instabihty of the free acid, it is usually prepared as the hydrochloride salt, mp 224 °C (dec), dissociation constant p 3.25. 

Uses. Aspirin has analgesic, antiinflammatory, and antipyretic activity. It is used for the reHef of less severe types of pain, such as headache, neuritis, acute and chronic rheumatoid arthritis, and toothache. Aspirin can be purchased in a variety of OTC and prescription dosage forms made and formulated by many companies. Tablets, ie, buffered, plain, or enteric-coated, are the most familiar in the United States, but other forms such as powder and effervescent formulations are of considerable importance in other parts of the world. 

Cosmetics and Toiletries. Citric acid and bicarbonate are used in effervescent type denture cleansers to provide agitation by reacting to form carbon dioxide gas. Citric acid is added to cosmetic formulations to adjust the pH, act as a buffer, and chelate metal ions preventing formulation discoloration and decomposition (213—218). 

Calcium carbonate makes up the largest amount of deposit in many cooling water systems (Fig. 4.16) and can be easily detected by effervescence when exposed to acid. Deposits are usually heavily stratified, reflecting changes in water chemistry, heat transfer, and flow. Corrosion may be slight beneath heavy accumulations of fairly pure calcium carbonate, as such layers can inhibit some forms of corrosion. When nearly pure, calcium carbonate is white. However, calcium carbonates are often intermixed with silt, metal oxides, and precipitates, leading to severe underdeposit attack. 

Two unnamed alkaloids have also been deseribed. One was obtained by Bredemann in work on the alkaloids of white hellebore it occurred in the mother liquors from protoveratrine crystallisation and formed spherical aggregates of needles, m.p. 239-241°. The other was isolated by. Jacobs and Craig during a chromatographic analysis of residual, benzene-soluble alkaloids of green hellebore. It is represented by the formula C27H41 (39)04N, crystallises in six-sided platelets or flat needles, sinters about 130°, effervesces at 170-5°, and on further heating solidifies and finally melts at 272-4° it has [a]n ° — 78° (MeOH). 

Parts of pyrazine-2arboxylic acid is heated in a reaction vessel provided with an intake for Inert gas. The reaction mixture is heated in a bath held at 220°C and nitrogen is introduced. The solid material melts and effervesces and sublimed pyrazinamide vapors are carried out of the reaction vessel in the nitrogen stream. They are introduced into a suitably cooled condenser, condensing in the form of a white sublimate. After the reaction is proceeding vigorously the bath temperature is raised to 255 C and then gradually and slowly allowed to drop to 190°C over a period of time sufficient to permit the reaction to go substantially to completion. The sublimed pyrazinamide, if desired, is further purified by recrystallization from water or alcohol. 

Effervescent Tablets. Effervescent tablets are another means of supplying medications to the elderly. This type of formulation provides the patient with an easy-to-swallow product that is aesthetically pleasing (i.e., forms a clear solution, rather than a cloudy... 

Form an aerated tablet containing the AI, which effervesces with water... 

Tablets are solid dosage forms that are compressed or prepared by a sintering proeess, including sublingual, buccal, chewable, effervescent, and compressed tablets. Some of these ean be easily compoimded an example of a tablet triturate is as follows ...

Buccal dosage forms can be of the tablet, patch, gel, or ointment type and can be employed for local or systemic delivery. For local deliveiy, conventional dosage forms such as solutions and various types of tablets (immediate release, effervescent, etc.) are more suitable. These forms generally have uncontrolled drug release with subsequent variable absorption and short residence times, and may not provide sufficient bioavailability. Novel dosage forms such as adhesive tablets, patches, gels, and... 

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