Saccharin

Category

Sweetening agent

Molecular Formula

C7H5NO3S

Molecular Weight

183.18

Grade

Pharmceutical Excipients

Description

Saccharin occurs as odorless white crystals or a white crystalline powder. It has an intensely sweet taste, with a metallic or bitter aftertaste that at normal levels of use can be detected by approximately 25% of the population. The aftertaste can be masked by blending saccharin with other sweeteners.

UNII

C151H8M554

Chemical Name

1, 2-Benzisothiazol-3(2H)-one 1, 1-dioxide

CAS Number

81-07-2

Synonyms

1, 2-Benzisothiazolin-3-one 1, 1-dioxide; benzoic acid sulfimide; benzoic sulfimide; benzosulfimide; 1, 2-dihydro-2-ketobenzisosulfonazole; 2, 3-dihydro-3-xobenzisosulfonazole; E954; Garantose; gluside; Hermesetas; sacarina; saccarina; saccharin insoluble; saccharinum; o-sulfobenzimide; o-sulfobenzoic acid imide.

Administration route

Oral; Topical

Dosage Form

Oral solutions, syrups, tablets, and topical preparations

Stability and Storage Conditions

Saccharin is stable under the normal range of conditions employed in formulations. In the bulk form it shows no detectable decomposition and only when it is exposed to a high temperature (125℃) at a low pH (pH 2) for over 1 hour does significant decomposition occur. The decomposition product formed is (ammonium-o-sulfo)benzoic acid, which is not sweet. The aqueous stability of saccharin is excellent. Saccharin should be stored in a well-closed container in a dry place.

Source and Preparation

Saccharin is prepared from toluene by a series of reactions known as the Remsen-Fahlberg method. Toluene is first reacted with chlorosulfonic acid to form o-toluenesulfonyl chloride, which is reacted with ammonia to form the sulfonamide. The methyl group is then oxidized with dichromate, yielding o-sulfamoylbenzoic acid, which forms the cyclic imide saccharin when heated.An alternative method involves a refined version of the Maumee process. Methyl anthranilate is initially diazotized to form 2-carbomethoxybenzenediazonium chloride; sulfonation followed by oxidation then yields 2-carbomethoxybenzenesulfonyl chloride.Amidation of this material, followed by acidification, forms insoluble acid saccharin.

Applications

Saccharin is an intense sweetening agent used in beverages, food products, table-top sweeteners, and oral hygiene products such as toothpastes and mouthwashes. In oral pharmaceutical formulations, it is used at a concentration of 0.02-0.5% w/w. It has been used in chewable tablet formulations as a sweetening agent.Saccharin has been used to form various pharmaceutical cocrystals. Saccharin can be used to mask some unpleasant taste characteristics or to enhance flavor systems. Its sweetening power is approximately 300-600 times that of sucrose.

Safety

There has been considerable controversy concerning the safety of saccharin, which has led to extensive studies since the mid-1970s.Two-generation studies in rats exposed to diets containing 5.0-7.5% total saccharin (equivalent to 175 g daily in humans) suggested that the incidence of bladder tumors was significantly greater in saccharin-treated males of the second generation than in controls.Further experiments in rats suggested that a contaminant of commercial saccharin, o-toluene sulfonamide, might also account for carcinogenic effects. In view of these studies, a ban on the use of saccharin was proposed in several countries. Adverse reactions to saccharin, although relatively few in relation to its widespread use, include: urticaria with pruritus following ingestion of saccharin-sweetened beverages and photosensitization reactions.
LD50 (mouse, oral): 17.5 g/kg
LD50 (rat, IP): 7.10 g/kg
LD50 (rat, oral): 14.2 g/kg

Incompatibilities

Saccharin can react with large molecules, resulting in a precipitate being formed. It does not undergo Maillard browning.