General methods for the preparation of effervescent granules are discussed briefly and a new adaptation of an old rocedure is presented. The use of a special mixer in simplifyin the initial blen&ng, heating, and screening steps of granulations made by the gsion method is described. No external heat source is required, nor are li uids in any form used to accomplish the granulating. The instrumentation, basicqormulation data, the method for monitoring the fusion process in the mixer, and the advantages of the new procedure are reported. Process data for granulation batch sizes of 60 and 300 kg. are given.
FFERVESCENT SALTS have been known and E used for about 130 years. Their popularity with the medical profession and the public has varied widely during this period. The preference for this dosage form declined markedly after reaching a peak during the early 19OO's, but a significant number of ethical and proprietary products have since created or maintained considerable popularity in the market place.
Effervescent combinations consisting of a medicinal agent, a dry, nontoxic organic acid such as citric or tartaric acid, and a n alkali metal carbonate or bicarbonate obviously cannot be wet granulated with aqueous solvent systems in the usual manner. With the exception of an experimental technique described by Coletta and Kennon (1) in 1964 which utilized the Wurster air-suspension apparatus, methods for preparing dervescent granules generally follow one of three approaches. The common goal of all three approaches is the introduction of just enough water to initiate a reaction between the acidic and basic components of a formulation, thereby massing it. The "wet method" utilizes a nonsolvent liquid such as alcohol, containing a small percentage of water. The "steam method" makes use of steam to add controlled amounts of water to the mixing material. The "fusion method" employs heat to liberate water of crystallization from components such as hydrous citric acid to elTect moistening.
The fusion method normally presents two major production problems. The first is the need for specialized equipment such as steam-heated hot plates, ovens, or externally heated coating ~~ -