PRODUCTS

MANNITOL

Mannitol is used as a flavor enhancer.
Mannitol is used as a filler in tablets.
Mannitol is used in very small quantities in vehicle engines as an anti-wear chemical, along with Monoethylene Glycol.

CAS Number: 69-65-8
EC Number: 200-711-8
MDL Number: MFCD00064287
E number: E421
Molecular Formula: C₆H₁₄O₆
Molecular Weight: 182.17 g/mol

SYNONYMS:
Osmitrol, Bronchitol, others, d-Mannitol, mannite, manna sugar, Aridol, Bronchitol, Cystosol, Osmitrol, Sag-M, D-mannitol, mannitol, 69-65-8, Mannite, Osmitrol, Manna sugar, 87-78-5, Cordycepic acid, Osmofundin, Resectisol, D-(-)-Mannitol, Mannit, Osmosal, Mannazucker, Mannidex, Mannigen, Mannistol, Diosmol, Invenex, Isotol, Mannitol, D-, Marine Crystal, (2R,3R,4R,5R)-hexane-1,2,3,4,5,6-hexol, Maniton-S, Mannogem 2080, (2R,3R,4R,5R)-Hexane-1,2,3,4,5,6-hexaol, Bronchitol, Mannitol (VAN), Aridol, Hexahydroxyhexane, DL-Mannitol, NCI-C50362, Mannitol (USP), Mannitol [USP], BRN 1721898, CHEBI:16899, MFCD00064287, 3OWL53L36A, INS NO.421, 133-43-7, E-421, mannitol-d, INS-421, Mannitol 5%, NSC-407017, Mannitol, 1,2,3,4,5,6-Hexanehexol, Mannitol 10%, Mannitol 15%, Mannitol 20%, NCGC00164246-01, E421, Mannidex 16700, DSSTox_CID_3235, Osmitrol 5% In Water, DSSTox_RID_76936, Osmitrol 10% In Water, Osmitrol 15% In Water, Osmitrol 20% In Water, DSSTox_GSID_23235, 287100-73-6, MTL, MANNITOL 25%, 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D-Mannitol - EP, HSDB 714, SR-01000838849, NSC 9256, EINECS 200-711-8, EINECS 201-770-2, NSC 407017, hexanehexol, UNII-3OWL53L36A, Cordycepate, D-mitobronitol, AI3-19511, Maniton s, Mannit p, Mannitol CRS, D-?Mannitol, Bronchitol (TN), (D)-mannitol, Mannitol 25, Mannitol 35, Mannitol 60, D(-)Mannitol, Pearlitol 25 c, Pearlitol 50 c, Mannitol m300, Pearlitol 160 c, Mannitol 200, Mannitol 300, Pearlitol 200 sd, Pearlitol 300 dc, Mannitol 2080, D-Mannit 1000 microg/mL in Methanol, D-Mannitol (Osmitrol), D-Mannitol (JP18), MANNITOL [HSDB], MANNITOL [FCC], Crystalline mannitol fine, MANNITOL [II], MANNITOL [MI], CCFD200109Mannitol, MANNITOL [VANDF], D-Mannitol, ACS reagent, D-Mannitol, >=98%, M0044, D-MANNITOL [JAN], MANNITOL [MART.], SCHEMBL919, bmse000099, CHEMBL689, Epitope ID:114705, MANNITOL [USP-RS], MANNITOL [WHO-DD], Isomalt impurity, mannitol-, Crystalline mannitol standard, D-MANNITOL [WHO-IP], 4-01-00-02841 (Beilstein Handbook Reference), ED1D1E61-FEFB-430A-AFDC-D1F4A957FC3D, MLS001335977, MLS001335978, D-Mannitol, Biochemical grade, Crystalline mannitol extra-fine, MANNITOL [EP IMPURITY], MANNITOL [ORANGE BOOK], D-Mannitol, AR, >=99%, D-Mannitol, LR, >=99%, orb1302416, orb1310638, orb3025617, orb3139589, MANNITOL [EP MONOGRAPH], MANNITOL [USP MONOGRAPH], SCHEMBL19304988, DTXSID30858955, MSK3101, MANNITOLUM [WHO-IP LATIN], HMS2230N11, HY-N0378, Tox21_112092, Tox21_201487, Tox21_300483, EBC-11056, AKOS006280947, D-Mannitol, plant cell culture tested, Tox21_112092_1, CCG-266445, D-Mannitol, BioXtra, >=98% (GC), DB00742, MM02190, MM63310, D-Mannitol tested according to Ph.Eur., D-Mannitol, NIST(R) SRM(R) 920, ISOMALT IMPURITY B [EP IMPURITY], NCGC00164246-03, NCGC00164246-04, NCGC00164246-05, NCGC00164246-18, NCGC00254277-01, NCGC00259038-01, 85085-15-0, AC-12776, AC-14054, AS-30501, D-Mannitol, tested according to Ph.Eur., DA-65240, D-Mannitol, p.a., 96.0-101.5%, D-Mannitol, SAJ first grade, >=99.0%, SORBITOL-MANNITOL COMPONENT MANNITOL, D-Mannitol, SAJ special grade, >=99.0%, E 421, NS00068035, S2381, SW220287-1, T0414, C00392, D00062, EN300-212188, AB00443917_06, F215993, ISOMALT IMPURITY, MANNITOL- [USP IMPURITY], Q407646, SR-01000838849-3, SR-01000838849-4, BRD-K30374899-001-09-3, D-Mannitol, ACS reagent, for microbiology, >=99.0%, LACTITOL MONOHYDRATE IMPURITY C [EP IMPURITY], D-Mannitol, meets EP, FCC, USP testing specifications, Mannitol, European Pharmacopoeia (EP) Reference Standard, Z1198149813, D-Mannitol, BioUltra, >=99.0% (sum of enantiomers, HPLC), Mannitol, United States Pharmacopeia (USP) Reference Standard, D-Mannitol, >=99.9999% (metals basis), for boron determination, Mannitol, Pharmaceutical Secondary Standard, Certified Reference Material, myo-Inositol EP Impurity A, Xylitol EP Impurity C, (2R,3R,4R,5R)-hexane-1,2,3,4,5,6-hexaol, NSC 9256, (2R,3R,4R,5R)-hexane-1,2,3,4,5,6-hexaol/(2S,3S,4S,5S)-hexane-1,2,3,4,5,6-hexaol, Osmitrol, 87-78-5, Manna Sugar, Cordycepic Acid, Sea Crystal, Maniton-S, Osmofundin

Mannitol is a versatile compound used in a variety of industrial and medical applications.
However, it is important to consult with a qualified healthcare professional before taking any supplement or using Mannitol for medical purposes.
Further research into the health effects and potential uses of mannitol is expected in the future.

Mannitol inhalation is used in patients 6 years of age and older to help diagnose asthma.
Mannitol is used in a procedure called bronchial challenge test to help your doctor measure the effect of this medicine on your lungs and check if you have difficulty with breathing.
Mannitol has 50% more sweetness than sucrose.

Mannitol is a naturally occurring substance in fruits and vegetables.
Mannitol does not have cariogenic properties.
Mannitol is a hexahydric alcohol derivative.

Mannitol is also found in mushrooms.
In these areas, Mannitol's role is as a sugar and carbohydrate reserve.
Mannitol is a derivative of the compound sorbitol.

The E code of Mannitol is E 421.
Mannitol is a sugar alcohol used to test for asthma, to reduce intracranial and intraocular pressure, to measure glomerular filtration rate, and to manage pulmonary symptoms associated with cystic fibrosis.
Mannitol is an osmotic diuretic that is metabolically inert in humans and occurs naturally, as a sugar or sugar alcohol, in fruits and vegetables.

Mannitol elevates blood plasma osmolality, resulting in enhanced flow of water from tissues, including the brain and cerebrospinal fluid, into interstitial fluid and plasma.
As a result, cerebral edema, elevated intracranial pressure, and cerebrospinal fluid volume and pressure may be reduced.
Mannitol appears as odorless white crystalline powder or free-flowing granules.

Mannitol has a role as a member of compatible osmolytes, a metabolite, an antiglaucoma drug, an osmotic diuretic, a sweetening agent, an allergen, a hapten, an Escherichia coli metabolite, a food anticaking agent, a food stabiliser, a food humectant, a food thickening agent and a food bulking agent.
Mannitol is a metabolite found in or produced by Escherichia coli (strain K12, MG1655).

Mannitol is an Osmotic Diuretic.
The mechanism of action of mannitol is as an Osmotic Activity.
The physiologic effect of mannitol is by means of Increased Diuresis.

Mannitol has been reported in Pisolithus tinctorius, Talaromyces verruculosus, and other organisms with data available.
Mannitol is a naturally occurring alcohol found in fruits and vegetables and used as an osmotic diuretic.
Mannitol is freely filtered by the glomerulus and poorly reabsorbed from the renal tubule, thereby causing an increase in osmolarity of the glomerular filtrate.

An increase in osmolarity limits tubular reabsorption of water and inhibits the renal tubular reabsorption of sodium, chloride, and other solutes, thereby promoting diuresis.
In addition, mannitol elevates blood plasma osmolarity, resulting in enhanced flow of water from tissues into interstitial fluid and plasma.
Mannitol is a chemical compound known as a sugar alkaloid, commonly found in nature in sugary fruits and other plants.

Mannitol is a naturally occurring sugar alcohol (polyol) widely distributed in plants, algae, and fungi.
Industrially, Mannitol is produced by hydrogenation of fructose or invert sugar.
Mannitol is valued for its low caloric content, chemical stability, and unique physicochemical properties, making it an important compound in food, pharmaceutical, and medical applications.

Mannitol is a type of sugar alcohol used as a sweetener and medication.
The discovery of mannitol is attributed to Joseph Louis Proust in 1806.
Mannitol is on the World Health Organization's List of Essential Medicines.

Mannitol was originally made from the flowering ash and called manna due to its supposed resemblance to the Biblical food.
Mannitol is on the World Anti-Doping Agency's banned substances list due to concerns that it may mask prohibited drugs.
Mannitol is a natural constituent of most microorganisms and plants, having an essential role in maintaining cell and tissue water balance, and responding to environmental stresses, such as drought or low temperature.

Mannitol is a diuretic medication that helps you make more pee to get rid of excess water in your body.
A healthcare provider will give you tMannitol in a hospital or clinic setting.
Mannitol treats swelling from heart, kidney or liver disease or swelling around your brain or in your eyes.

Mannitol is less hygroscopic than sorbitol, which makes it particularly useful in moisture-sensitive formulations.
Mannitol is also frequently used in chewable tablets because of its pleasant taste and mouthfeel.

Environmentally, mannitol is biodegradable and does not accumulate in ecosystems.
Mannitol's production is well-established and scalable, often involving catalytic hydrogenation processes.

USES and APPLICATIONS of MANNITOL:
In the pharmaceutical industry, its non-hygroscopic properties make Mannitol a key component in the manufacture of chewable tablets.
Mannitol is used in the production of chewing gum containing medication.
Mannitol's sweetening agent properties are utilized.

Mannitol is used in the manufacture of medications produced to treat swelling that occurs around the brain and inside the eyes.
Some people have difficulty producing urine in their bodies.
Mannitol is used in the manufacture of medications that help the body produce urine.

Patients with kidney failure are given medications containing Mannitol.
These medications help remove excess water and toxins from the body.
Mannitol is used in the manufacture of these medications.

Mannitol is used as an anti-caking agent in the food industry.
Mannitol is used as a flavoring agent in nut production.
Due to its neutral taste, Mannitol is used as a filler in chewable tablets, orally disintegrating tablets, and swallowable tablets.

Sugar alcohols used in antifreeze production include alcohols such as mannitol, dextrose, maltitol, and sorbitol.
Increasing the dextrose equivalent will increase water activity and inhibit water crystallization.
This will lower the freezing point.

Mannitol is used as a flavor enhancer.
Mannitol is used as a filler in tablets.
Mannitol is used in very small quantities in vehicle engines as an anti-wear chemical, along with Monoethylene Glycol.

Mannitol has broad applications across industries.
In the food industry, Mannitol is used as a low-calorie sweetener and bulking agent in sugar-free products such as chewing gum, candies, coatings, and bakery items.
Mannitol's cooling effect enhances sensory properties in confectionery.

In the pharmaceutical industry, mannitol is widely used as an excipient, particularly in tablet formulations, due to its compressibility and stability.
Mannitol is also used in lyophilized (freeze-dried) drug formulations as a bulking agent.
Medically, mannitol plays a critical role as an osmotic diuretic.

Mannitol is used intravenously to reduce intracranial pressure, treat cerebral edema, and promote urine production in cases of acute renal failure.
Mannitol is also used to reduce intraocular pressure in glaucoma treatment.
Additionally, mannitol is used in diagnostic applications such as bronchial provocation tests.

Mannitol is the primary ingredient of mannitol salt agar, a bacterial growth medium, and is used in others.
Mannitol is used as a cutting agent in various drugs that are used intranasally (snorted), such as heroin and cocaine.
A mixture of mannitol and fentanyl (or fentanyl analogs) in ratio 1:10 is labeled and sold as "China white", a popular heroin substitute.

Mannitol is a sugar alcohol with "50–70 percent of the relative sweetness of sugar, which means more must be used to equal the sweetness of sugar.
Mannitol lingers in the intestines for a long time and therefore often causes bloating and diarrhea.
Oral: Mannitol acts as an osmotic laxative in oral doses larger than 20 g, and is sometimes sold as a laxative for children.

Mannitol is commonly used in the circuit prime of a heart lung machine during cardiopulmonary bypass.
The presence of mannitol preserves renal function during the times of low blood flow and pressure, while the patient is on bypass.
The solution prevents the swelling of endothelial cells in the kidney, which may have otherwise reduced blood flow to this area and resultant cell damage.

Mannitol can also be used to temporarily encapsulate a sharp object (such as a helix on a lead for an artificial pacemaker) while it passes through the venous system.
Because the mannitol dissolves readily in blood, the sharp point becomes exposed at its destination.
Intra-arterial infusions of mannitol can transiently open the blood–brain barrier by disrupting tight junctions.

Mannitol is also the first drug of choice to treat acute glaucoma (high eye pressure) in veterinary medicine.
Mannitol is administered as a 20% solution intravenously.
Mannitol dehydrates the vitreous humor and, therefore, lowers the intraocular pressure.

However, Mannitol requires an intact blood-ocular barrier to work.
Mannitol is used as a low-calorie sweetener as it is poorly absorbed by the intestines.
As a medication, Mannitol is used to decrease pressure in the eyes, as in glaucoma, and to lower increased intracranial pressure.

Medically, Mannitol is given by injection or inhalation.
Effects typically begin within 15 minutes and last up to 8 hours.
Mannitol may also be used for the promotion of diuresis before irreversible renal failure becomes established; the promotion of urinary excretion of toxic substances; as an Antiglaucoma agent; and as a renal function diagnostic aid.

Mannitol is an agent used as an osmotic diuretic that, when administered intravenously, increases plasma osmolarity, expanding extracellular fluid volume and thus facilitating the passage of water out of the cells.
Because of this property, Mannitol is effective in reducing intracranial and intraocular pressure.

-Medical uses of Mannitol:
*Injected
In the United States, injected mannitol is indicated for the reduction of intracranial pressure and treatment of cerebral edema and elevated intraocular pressure.
Mannitol is used intravenously to reduce acutely raised intracranial pressure until more definitive treatment can be applied, e.g., after head trauma.
While mannitol injection is the mainstay for treating high pressure in the skull after a serious brain injury, it is no better than hypertonic saline as a first-line treatment.

In treatment-resistant cases, hypertonic saline works better.
It may also be used for certain cases of kidney failure with low urine output, to decrease pressure in the eye, to increase the elimination of certain toxins, and to treat fluid build up.
Intraoperative mannitol prior to vessel clamp release during renal transplant has been shown to reduce post-transplant kidney injury, but has not been shown to reduce graft rejection.

-Food uses of Mannitol:
Mannitol increases blood glucose to a lesser extent than sucrose (thus having a relatively low glycemic index) so is used as a sweetener for people with diabetes, and in chewing gums.
Although mannitol has a higher heat of solution than most sugar alcohols, its comparatively low solubility reduces the cooling effect usually found in mint candies and gums.
However, when mannitol is completely dissolved in a product, it induces a strong cooling effect.

Also, it has a very low hygroscopicity – it does not pick up water from the air until the humidity level is 98%.
This makes mannitol very useful as a coating for hard candies, dried fruits, and chewing gums, and it is often included as an ingredient in candies and chewing gum.
The pleasant taste and mouthfeel of mannitol also makes it a popular excipient for chewable tablets.

-Analytical chemistry uses of Mannitol:
Mannitol forms stable complexes with boric acid.
This considerably enhances the acidity of boric acid, allowing for greater precision in the volumetric titration of this acid.

The stability of the mannitoborate ester anions shifts the acid dissociation equilibrium to the right, thereby increasing the solution's acidity by five orders of magnitude compared to that of pure boric acid.
This lowers the pKa from 9 to below 4 for a sufficient concentration of mannitol.
The resulting solution is referred to as mannitoboric acid.

USES AND BENEFITS OF MANNITOL:
The benefits of mannitol extend beyond its role as a pharmaceutical excipient.
Due to its osmotic diuretic properties, Mannitol is widely used in medicine, particularly in the treatment of conditions such as cerebral edema and increased intracranial pressure.
Mannitol helps reduce swelling and relieve pressure on the brain by drawing water from cells into the bloodstream.

In addition, mannitol is used in the treatment of acute kidney injury, where it helps maintain urine flow and prevent kidney failure.
In the field of nutrition, mannitol acts as a low-calorie sweetener, making it an attractive alternative for those who want to reduce sugar intake without sacrificing flavor.
Its sweetness is approximately 50-70% of sucrose, and Mannitol is commonly used in sugar-free products such as candies, gums, and baked goods.
The use of mannitol as an artificial sweetener is particularly beneficial for people with diabetes, as it does not cause significant increases in blood sugar levels.

UNDERSTANDING MANNITOL AND ITS APPLICATIONS:
Mannitol is a polyol commonly obtained from the fermentation of sugars.
Mannitol is known for its unique properties, including its ability to act as a diuretic, sweetener, and stabilizer in various formulations.
In the pharmaceutical industry, mannitol is primarily used as an excipient, a substance formulated alongside the active ingredient of a drug.
Its low caloric content and non-decaying nature make Mannitol an ideal choice for formulations aimed at diabetics and those seeking to reduce sugar intake.
Furthermore, mannitol's ability to improve the solubility and stability of drugs makes it a valuable component in the development of oral and injectable medications.

PHARMACOLOGICAL PROPERTIES OF MANNITOL:
Chemical Structure and Pharmacokinetic Properties:
Mannitol is a six-carbon sugar alcohol and is minimally metabolized in the body.
Mannitol is eliminated by glomerular filtration and does not bind to plasma proteins.
Mannitol's half-life is approximately 100 minutes, but can be extended up to 36 hours in renal failure.

***Mechanism of Action:
Mannitol undergoes filtration in the renal tubules without being reabsorbed, increasing the osmolarity of the tubular fluid and inhibiting water reabsorption.
This leads to diuresis.
Furthermore, because Mannitol cannot cross the blood-brain barrier, it promotes the passage of water from brain tissue into the plasma, thereby reducing intracranial pressure.

***Indications for Mannitol
Increased Intracranial Pressure and Cerebral Edema:
Mannitol is used in the treatment of cerebral edema and increased intracranial pressure.
Mannitol's effect begins 15 minutes after administration and can last 3-8 hours.

***Increased Intraocular Pressure:
Mannitol is used to reduce intraocular pressure in conditions such as glaucoma.
Mannitol's effect begins 15 minutes after injection and reaches its maximum within 30-60 minutes.

***Acute Renal Failure:
Mannitol is used to increase urine output to prevent or treat the oliguric phase.

***Toxic Substance Excretion:
Mannitol is used to increase the excretion of toxic substances in urine and for irrigation of the urinary tract.

BENEFITS of MANNITOL:
Mannitol provides several functional and therapeutic benefits:
Suitable for diabetic and low-calorie diets
Mannitol supports oral health by not promoting dental caries
Mannitol enhances stability and shelf life of formulations
Mannitol provides osmotic therapeutic effects in medicine
Mannitol improves texture and mouthfeel in food products

CHARACTERISTICS of MANNITOL:
*Mannitol is characterized by:
*Low glycemic index and minimal impact on blood glucose levels
*Non-cariogenic properties
*Low hygroscopicity
*High chemical and thermal stability
*Cooling effect due to endothermic dissolution
*Osmotic activity in biological systems

WHAT ARE THEIR PHYSICAL AND CHEMICAL PROPERTIES
Physically, Mannitol is in the form of a white crystalline powder.
Mannitol can also be found in granular form.
Mannitol has a sweet taste.
Mannitol has an aroma.

Mannitol's melting point is 168 °C.
Mannitol's boiling point is between 290 °C and 295 °C.
Mannitol has a solubility of 216 g/L at 25 °C.

Mannitol's solubility increases with increasing temperature.
Mannitol's solubility in glycerin is 1 g/18 ml.
Mannitol's density is 1.52 g/cm³ at 20 °C.

HOW IS MANNITOL PRODUCED?
There are several methods for producing mannitol.
These include the electrolytic reduction of glucose or the hydrogenation of invert sugar, monosaccharides, or sucrose.
Commercially, Mannitol is produced by the catalytic or electrolytic reduction of monosaccharides such as glucose or mannose.

METHODS OF OBTAINING of MANNITOL:
Mannitol is usually obtained by extraction from plants or isolation from high-fructose corn syrup.
Mannitol can also be produced synthetically, but is generally derived from natural sources.

PHYSICAL AND CHEMICAL PROPERTIES of MANNITOL:
Mannitol is a white, crystalline, odorless powder with a sweet taste, approximately 50–70% as sweet as sucrose.
Mannitol is highly stable under standard conditions and exhibits a high melting point of about 165–170°C.

Mannitol is freely soluble in water but only slightly soluble in alcohol and practically insoluble in most organic solvents.
Mannitol is non-hygroscopic or only slightly hygroscopic, which makes it highly suitable for solid dosage forms and powdered food products.
Chemically, mannitol is a hexitol (six-carbon sugar alcohol) derived from mannose.

Mannitol is a non-reducing compound and does not readily participate in Maillard reactions, contributing to its stability during heat processing.
Its aqueous solutions are neutral, and Mannitol exhibits low reactivity under normal conditions.
Mannitol also has a negative heat of solution, producing a cooling sensation when dissolved, which is beneficial in certain food and pharmaceutical formulations.

WHAT IS MANNITOL AND HOW IS IT OBTAINED?
Chemical Structure and Formula
Mannitol is a sugar alkaloid with the chemical formula C6H14O6.
Mannitol occurs naturally, particularly in manna ash (Fraxinus ornus) and some other plants.

BIOSYNTHESES of MANNITOL:
Mannitol is one of the most abundant energy and carbon storage molecules in nature, produced by a plethora of organisms, including bacteria, yeasts, fungi, algae, lichens, and many plants.
It is a natural constituent of most microorganisms and plants, having roles in maintaining cellular water balance, and responding to drought or low temperature.
Fermentation by microorganisms is an alternative to the traditional industrial synthesis.

A fructose-to-mannitol metabolic pathway, known as the mannitol cycle in fungi, has been discovered in a type of red algae (Caloglossa leprieurii), and it is highly possible that other microorganisms employ similar such pathways.
A class of lactic acid bacteria, labeled heterofermentive because of their multiple fermentation pathways, convert either three fructose molecules or two fructose and one glucose molecule into two mannitol molecules, and one molecule each of lactic acid, acetic acid, and carbon dioxide.

Feedstock syrups containing medium to large concentrations of fructose (for example, cashew apple juice, containing 55% fructose: 45% glucose) can produce yields 200 g mannitol per liter of feedstock.
Further research is being conducted, studying ways to engineer even more efficient mannitol pathways in lactic acid bacteria, as well as the use of other microorganisms such as yeast and E. coli in mannitol production.

When food-grade strains of any of the aforementioned microorganisms are used, the mannitol and the organism itself are directly applicable to food products, avoiding the need for careful separation of microorganism and mannitol crystals.
Although this is a promising method, steps are needed to scale it up to industrially needed quantities.

NATURAL EXTRACTION of MANNITOL:
Since mannitol is found in a wide variety of natural products, including almost all plants, it can be directly extracted from natural products, rather than chemical or biological syntheses.
In fact, in China, isolation from seaweed is the most common form of mannitol production.
Mannitol concentrations of plant exudates can range from 20% in seaweeds to 90% in the plane tree.

Mannitol is a constituent of saw palmetto (Serenoa).
Traditionally, mannitol is extracted from the crude material in a Soxhlet apparatus using a mixture of ethanol, water, and methanol.
The mannitol is then recrystallized from the extract, generally resulting in yields of about 18% of the original natural product.

Another method of extraction is using supercritical and subcritical fluids.
These fluids are at such a stage that no difference exists between the liquid and gas stages, so are more diffusive than normal fluids.
This is considered to make them much more effective mass transfer agents than normal liquids.

The super- or subcritical fluid is pumped through the natural product, and the mostly mannitol product is easily separated from the solvent and minute amount of byproduct.
Supercritical carbon dioxide extraction of olive leaves has been shown to require less solvent per measure of leaf than a traditional extraction – 141.7 g CO2 versus 194.4 g ethanol per 1 g olive leaf.
Heated, pressurized, subcritical water is even cheaper, and is shown to have dramatically greater results than traditional extraction.

It requires only 4.01 g water per 1 g of olive leaf, and gives a yield of 76.75% mannitol.
Both super- and subcritical extractions are cheaper, faster, purer, and more environmentally friendly than the traditional extraction.
However, the required high operating temperatures and pressures are causes for hesitancy in the industrial use of this technique.

CHEMISTRY of MANNITOL:
Mannitol is an isomer of sorbitol, another sugar alcohol; the two differ only in the orientation of the hydroxyl group on carbon 2.
While similar, the two sugar alcohols have very different sources in nature, melting points, and uses.

PRODUCTION of MANNITOL:
Mannitol is classified as a sugar alcohol; that is, it can be derived from a sugar (mannose) by reduction.
Other sugar alcohols include xylitol and sorbitol.

INDUSTRIAL SYNTHESIS of MANNITOL:
Mannitol is commonly produced via the hydrogenation of fructose, which is formed from either starch or sucrose (common table sugar).
Although starch is a cheaper source than sucrose, the transformation of starch is much more complicated.
Eventually, it yields a syrup containing about 42% fructose, 52% glucose, and 6% maltose.
Sucrose is simply hydrolyzed into an invert sugar syrup, which contains about 50% fructose.

In both cases, the syrups are chromatographically purified to contain 90–95% fructose.
The fructose is then hydrogenated over a nickel catalyst into a mixture of isomers sorbitol and mannitol.
Yield is typically 50%:50%, although slightly alkaline reaction conditions can slightly increase mannitol yields.

HISTORY of MANNITOL:
In the early 1880s, Julije Domac elucidated the structure of hexene and mannitol obtained from Caspian manna.
He determined the place of the double bond in hexene obtained from mannitol and proved that it is a derivative of a normal hexene.
This also solved the structure of mannitol, which was unknown until then.

PHYSICAL and CHEMICAL PROPERTIES of MANNITOL:
Molar mass: 182.172 g·mol−1
Molecular Weight: 182.17
XLogP3: -3.1
Hydrogen Bond Donor Count: 6
Hydrogen Bond Acceptor Count: 6
Rotatable Bond Count: 5
Exact Mass: 182.07903816
Monoisotopic Mass: 182.07903816
Topological Polar Surface Area: 121 Å²
Heavy Atom Count: 12

Formal Charge: 0
Complexity: 105
Isotope Atom Count: 0
Defined Atom Stereocenter Count: 4
Undefined Atom Stereocenter Count: 0
Defined Bond Stereocenter Count: 0
Undefined Bond Stereocenter Count: 0
Covalently-Bonded Unit Count: 1
Compound Is Canonicalized: Yes

Appearance Form: powder
Color: white
Odor: No data available
Odor Threshold: No data available
pH: 5,0 - 6,5 at 182 g/l at 25 °C
Melting point/freezing point:
Melting point/range: 167 - 170 °C
Initial boiling point and boiling range: 290 - 295 °C at 4,67 hPa
Flash point: No data available
Evaporation rate: No data available

Flammability (solid, gas): No data available
Upper/lower flammability or explosive limits: No data available
Vapor pressure: No data available
Vapor density: No data available
Relative density: No data available
Water solubility: 182 g/l at 20 °C - completely soluble
Partition coefficient: n-octanol/water: No data available
Autoignition temperature: No data available
Decomposition temperature: No data available

Viscosity
Viscosity, kinematic: No data available
Viscosity, dynamic: No data available
Explosive properties: No data available
Oxidizing properties: No data available
Other safety information: No data available
Appearance: White crystalline powder
Assay (%): 98.0-102.0
Loss on drying (%): ≤0.5
Specific rotation: +23~+25°

Heavy metal (Pb) (%): <10ppm
Arsenic (%): ≤0.0002
Nickel (%): ≤ 0.30
Oxalate (%): <0.02
Sulfate (SO4) (%): ≤0.01
Chloride (Cl) (%): ≤0.003
Melting point ( ℃): 166-170 °C
Acidity: Conform
Residue on ignition: (%) <0.1
Storage in the shade

Synonyms: D-mannitol; Mannite; Osmitrol
IUPAC Name: (2R,3R,4R,5R)-hexane-1,2,3,4,5,6-hexol
Molecular Weight: 182.17
Molecular Formula: C6H14O6
Canonical SMILES: C(C(C(C(C(CO)O)O)O)O)O
InChI: InChI=1S/C6H14O6/c7-1-3(9)5(11)6(12)4(10)2-8/h3-12H,1-2H2/t3-,4-,5-,6-/m1/s1
InChIKey: FBPFZTCFMRRESA-KVTDHHQDSA-N
Boiling Point: 295°C

Melting Point: 165-167°C
Flash Point: 100°C
Purity: 98%
Density: 1.52
Solubility: Soluble in DMSO (slightly), methanol (slightly), water.
Appearance: White Solid
Storage: Freezer
Assay: 0.99

EMPIRICAL FORMULA (HILL NOTATION): C6H14O6
CAS NUMBER: 69-65-8
MOLECULAR WEIGHT: 182.17
UNSPSC CODE: 12352201
NACRES: NA.21
PUBCHEM SUBSTANCE ID: 24896902
EC NUMBER: 200-711-8
BEILSTEIN/REAXYS NUMBER: 1721898

MDL NUMBER: MFCD00064287
MOLECULAR WEIGHT 182.17 g/mol
XLOGP3 -3.1
HYDROGEN BOND DONOR COUNT 6
HYDROGEN BOND ACCEPTOR COUNT 6
ROTATABLE BOND COUNT 5
EXACT MASS 182.07903816 Da
MONOISOTOPIC MASS 182.07903816 Da
TOPOLOGICAL POLAR SURFACE AREA 121 Å²

HEAVY ATOM COUNT 12
FORMAL CHARGE 0
COMPLEXITY 105
ISOTOPE ATOM COUNT 0
DEFINED ATOM STEREOCENTER COUNT 4
UNDEFINED ATOM STEREOCENTER COUNT 0
DEFINED BOND STEREOCENTER COUNT 0
UNDEFINED BOND STEREOCENTER COUNT 0
COVALENTLY-BONDED UNIT COUNT 1
COMPOUND IS CANONICALIZED Yes

FIRST AID MEASURES of MANNITOL:
-Description of first-aid measures:
*If inhaled:
After inhalation:
Fresh air.
*In case of skin contact:
Take off immediately all contaminated clothing.
Rinse skin with water/ shower.
*In case of eye contact:
After eye contact:
Rinse out with plenty of water.
Remove contact lenses.
*If swallowed:
After swallowing:
Make victim drink water (two glasses at most).
Consult doctor if feeling unwell.
-Indication of any immediate medical attention and special treatment needed:
No data available

ACCIDENTAL RELEASE MEASURES of MANNITOL:
-Environmental precautions:
Do not let product enter drains.
-Methods and materials for containment and cleaning up:
Cover drains.
Collect, bind, and pump off spills.
Take up dry.
Dispose of properly.

FIRE FIGHTING MEASURES of MANNITOL:
-Extinguishing media:
*Suitable extinguishing media:
Water
Foam
Carbon dioxide (CO2)
Dry powder
*Unsuitable extinguishing media:
For this substance/mixture no limitations of extinguishing agents are given.
-Further information:
Prevent fire extinguishing water from contaminating surface water or the ground water system.

EXPOSURE CONTROLS/PERSONAL PROTECTION of MANNITOL:
-Control parameters:
--Ingredients with workplace control parameters:
-Exposure controls:
--Personal protective equipment:
*Eye/face protection:
Use Safety glasses
*Skin protection:
Full contact:
Material: Nitrile rubber
Minimum layer thickness: 0,11 mm
Break through time: 480 min
Splash contact:
Material: Nitrile rubber
Minimum layer thickness: 0,11 mm
Break through time: 480 min
-Control of environmental exposure:
Do not let product enter drains

HANDLING and STORAGE of MANNITOL:
-Conditions for safe storage, including any incompatibilities:
*Storage conditions:
Tightly closed.
Dry.

STABILITY and REACTIVITY of MANNITOL:
-Conditions to avoid:
no information available
-Incompatible materials:
No data available