Fructose

Category

flavoring Agents; Sweetening Agents; Diluent

Molecular Formula

C6H12O6

Molecular Weight

180.16

Grade

Pharmceutical Excipients

Description

Fructose occurs as odorless, colorless crystals or a white crystalline powder with a very sweet taste.

UNII

6YSS42VSEV

Chemical Name

D-Fructose

CAS Number

57-48-7

Synonyms

Advantose FS 95; D-arabino-2-hexulose; Fructamyl; Fructofin; D-(-)-fructopyranose; b-D-fructose; fructosum; fruit sugar; Krystar; laevulose; levulose; nevulose

Administration route

Intravenous, oral, rectal

Dosage Form

Oral solutions; syrup, and suspensions; rectal preparations; intravenous infusions

Stability and Storage Conditions

Fructose is hygroscopic and absorbs significant amounts of moisture at relative humidities greater than 60%. Goods stored in the original sealed packaging at temperatures below 25℃ and a relative humidity of less than 60% can be expected to retain stability for at least 12 months. Aqueous solutions are most stable at pH 3-4 and temperatures of 4-70℃; they may be sterilized by autoclaving.

Source and Preparation

Fructose, a monosaccharide sugar, occurs naturally in honey and a large number of fruits. It may be prepared from inulin, dextrose, or sucrose by a number of methods. Commercially, fructose is mainly manufactured by crystallization from high-fructose syrup derived from hydrolyzed and isomerized cereal starch or cane and beet sugar.

Applications

Fructose is used in tablets, syrups, and solutions as a flavoring and sweetening agent. The sweetness-response profile of fructose is perceived in the mouth more rapidly than that of sucrose and dextrose, which may account for the ability of fructose to enhance syrup or tablet fruit flavors and mask certain unpleasant vitamin or mineral ‘off-flavors’. The increased solubility of fructose in comparison to sucrose is advantageous in syrup or solution formulations that must be refrigerated, since settling or crystallization of ingredients is retarded. Similarly, the greater solubility and hygroscopicity of fructose over sucrose and dextrose helps to avoid ‘cap-locking’ (sugar crystallization around the bottle cap) in elixir preparations. Fructose also has greater solubility in ethanol (95%) and is therefore used to sweeten alcoholic formulations. The water activity of a sweetener influences product microbial stability and freshness. Fructose has a lower water activity and a higher osmotic pressure than sucrose. Syrup formulations may be made at lower dry-substance levels than sugar syrups without compromising shelf-life stability. It may be necessary to include a thickener or gelling agent to match the texture or viscosity of the sugar-equivalent formulation. Fructose is sweeter than the sugar alcohols mannitol and sorbitol, which are commonly used as tableting excipients.Although fructose is effective at masking unpleasant flavors in tablet formulations, tablets of satisfactory hardness and friability can only be produced by direct compression if tablet presses are operated at relatively slow speeds. However, by the combination of crystalline fructose with tablet-grade sorbitol in a 3.: 1.ratio, satisfactory direct-compression characteristics can be achieved. A directly compressible grade of fructose, containing a small amount of starch (Advantose FS 95, SPI Pharma) is also commercially available. Pregranulation of fructose with 3.5% povidone also produces a satisfactory tablet excipient.The added sweetness of fructose may also be used to advantage by coating the surface of chewable tablets, lozenges, or medicinal gums with powdered fructose. The coprecipitation of fructose with hydrophobic drugs such as digoxin has been shown to enhance the dissolution profile of such drugs. Fructose apparently acts as a water-soluble carrier upon coprecipitation, thereby allowing hydrophobic drugs to be more readily wetted.

Safety

Although it is absorbed more slowly than dextrose from the gastrointestinal tract, fructose is metabolized more rapidly. Metabolism of fructose occurs mainly in the liver, where it is converted partially to dextrose and the metabolites lactic acid and pyruvic acid.

Incompatibilities

Incompatible with strong acids or alkalis, forming a brown coloration. In the aldehyde form, fructose can react with amines, amino acids, peptides, and proteins. Fructose may cause browning of tablets containing amines.