Mannitol

• BPMannitol
• JPD-Mannitol
• Ph. Eur.Mannitol
• USP–NFMannitol

D-Mannitol; mannite; manna sugar; mannitolum; Mannogem; Parteck M; Pearlitol; E421

D-Mannitol · [69-65-8]

UNII 3OWL53L36A · PubChem CID 6251

C6H14O6 · 182.17

Diluent (filler), Tonicity-adjusting agent

Typical concentrations: 10–90% in tablets · Dosage forms: Solid, Sterile (parenteral/ophthalmic)

Widely used as a diluent in tablets and capsules (typically 10–90% w/w), particularly in chewable and orally disintegrating tablets, because it is non-hygroscopic, pleasantly sweet and gives a cooling sensation. It is a common bulking agent in freeze-dried injections, an isotonicity agent in parenterals and ophthalmics, and is used in direct-compression (granulated or spray-dried) grades and as a plasticiser in soft capsules. Therapeutically it is an osmotic diuretic.

White, odourless, crystalline powder or free-flowing granules with a sweet taste about half that of sucrose and a cooling mouthfeel.

Melting point

166–168 °C

Solubility

freely soluble in water (about 1 in 5.5 at 20 °C); very slightly soluble in ethanol; practically insoluble in ether

Polymorphism

α, β and δ forms; β is the stable commercial form

True density

≈ 1.51 g/cm³

Iso-osmotic concentration

≈ 5.07% w/v in water

Hygroscopicity

non-hygroscopic

Stable in the dry state and in aqueous solution; solutions may be autoclaved. Concentrated solutions (about 15–20% and above) can crystallise when cooled; crystals should be redissolved by warming and an in-line filter used for infusion. Store in a well-closed container in a cool, dry place.

Concentrated solutions (20–25%) may be salted out by potassium or sodium chloride, and mannitol should not be added to whole blood for transfusion. It can complex some metal ions (for example aluminium, copper and iron), and the reducing-sugar impurities of some grades have been linked to drug degradation. Mannitol has been reported to reduce the oral bioavailability of some drugs compared with sucrose.

Produced mainly by catalytic hydrogenation of fructose-containing sugar solutions (for example invert sugar), with separation of mannitol from sorbitol by crystallisation; it can also be extracted from seaweed.

Poorly absorbed orally; large oral doses (about 20 g or more) cause osmotic diarrhoea. Given intravenously it is filtered by the kidney and acts as an osmotic diuretic; excessive doses can cause fluid and electrolyte imbalance. Hypersensitivity reactions are rare.

Observe normal precautions for the quantity handled. Avoid generating dust; eye protection, gloves and a dust mask are recommended.

Accepted as a food additive in Europe (E421) and permitted in foods in the USA (21 CFR 180.25). Included in the FDA Inactive Ingredient Database (intravenous and other injections; inhalation; oral capsules, solutions and tablets; ophthalmic and topical preparations) and in parenteral and non-parenteral medicines licensed in Europe.

Sorbitol; xylitol; maltitol; isomalt; erythritol.

Powdered crystalline mannitol flows and compresses poorly, so granulated or spray-dried grades are used for direct compression. In freeze-drying, mannitol usually crystallises and gives an elegant cake; incomplete crystallisation or hemihydrate formation can affect stability, so the cycle must be designed accordingly.