Mannitol is a diluent, plasticizer, sweetening and tonicity agent that is widely used in pharmaceutical formulations and food products. This material is present in Arvin Kala’s diverse product portfolio.
Mannitol is D-mannitol. It is a hexahydric alcohol related to mannose and is isomeric with sorbitol.
Mannitol occurs as a white, odorless, crystalline powder, or free flowing granules. It has a sweet taste, approximately as sweet as glucose and half as sweet as sucrose, and imparts a cooling sensation in the mouth. Microscopically, it appears as orthorhombic needles when crystallized from alcohol. Mannitol shows polymorphism.
Applications in Pharmaceutical Formulation or Technology
Mannitol is widely used in pharmaceutical formulations and food products. In pharmaceutical preparations it is primarily used as a diluent (10 to 90% w/w) in tablet formulations, where it is of particular value since it is not hygroscopic and may thus be used with moisture-sensitive active ingredients.
Mannitol may be used in direct-compression tablet applications for which the granular and spray-dried forms are available, or in wet granulations.
Granulations containing mannitol have the advantage of being dried easily. Specific tablet applications include antacid preparations, glyceryl trinitrate tablets, and vitamin preparations. Mannitol is commonly used as an excipient in the manufacture of chewable tablet formulations because of its negative heat of solution, sweetness, and ‘mouth feel’.
In lyophilized preparations, mannitol (20 to 90% w/w) has been included as a carrier to produce a stiff, homogeneous cake that improves the appearance of the lyophilized plug in a vial. A pyrogen-free form is available specifically for this use.
Mannitol has also been used to prevent thickening in aqueous antacid suspensions of aluminum hydroxide. Â It is used in food applications as a bulking agent.
Therapeutically, mannitol administered parenterally is used as an osmotic diuretic, as a diagnostic agent for kidney function, as an adjunct in the treatment of acute renal failure, and as an agent to reduce intracranial pressure, treat cerebral edema, and reduce intraocular pressure. Given orally, mannitol is not absorbed significantly from the gastrointestinal tract, but in large doses it can cause osmotic diarrhea.
Stability and Storage Conditions
Mannitol is stable in the dry state and in aqueous solutions. Solutions may be sterilized by filtration or by autoclaving and if necessary may be autoclaved repeatedly with no adverse physical or chemical effects. In solution, mannitol is not attacked by cold, dilute acids or alkalis, nor by atmospheric oxygen in the absence of catalysts. Mannitol does not undergo Maillard reactions.
The bulk material should be stored in a well-closed container in a cool, dry place.
Method of Manufacture
Mannitol may be extracted from the dried sap of manna and other natural sources by means of hot alcohol or other selective solvents. It is commercially produced by the catalytic or electrolytic reduction of monosaccharides such as mannose and glucose.
Safety
Mannitol is a naturally occurring sugar alcohol found in animals and plants; it is present in small quantities in almost all vegetables. Laxative effects may occur if mannitol is consumed orally in large quantities. If it is used in foods as a bodying agent and daily ingestion of over 20 g is foreseeable, the product label should bear the statement ‘excessive consumption may have a laxative effect’. After intravenous injection, mannitol is not metabolized to any appreciable extent and is minimally reabsorbed by the renal tubule, about 80% of a dose being excreted in the urine in 3 hours.
A number of adverse reactions to mannitol have been reported, primarily following the therapeutic use of 20% w/v aqueous intravenous infusions. The quantity of mannitol used as an excipient is considerably less than that used therapeutically and is consequently associated with a lower incidence of adverse reactions. However, allergic, hypersensitive-type reactions may occur when mannitol is used as an excipient.
An acceptable daily intake of mannitol has not been specified by the WHO since the amount consumed as a sweetening agent was not considered to represent a hazard to health.
LD50 (mouse, IP): 14 g/kg
LD50 (mouse, IV): 7.47 g/kg
LD50 (mouse, oral): 22 g/kg
LD50 (rat, IV): 9.69 g/kg
LD50 (rat, oral): 13.5 g/kg
Handling Precautions
Observe normal precautions appropriate to the circumstances and quantity of material handled. Mannitol may be irritant to the eyes; eye protection is recommended.
Chemical-physical values
| TEST ITEM | Unit | Specification |
|---|---|---|
|
Appearance |
|
white crystalline powder |
|
Conductivity |
us/cm |
Max 20 |
|
Reducing sugars |
% |
Max 0.1 |
|
Nickel |
ppm |
Max 1 |
|
Loss on drying |
% |
Max 0.5 |
| TEST ITEM | Unit | Specification |
|---|---|---|
|
TAMC |
Cfu/g |
Max 1000 |
|
TYMC |
Cfu/g |
Max 100 |
|
Escherichia coli |
|
Negative |
|
Salmonella |
|
Negative |
|
Assay |
% |
Min 98.0 &
Max 102.0
|
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