Mannitol
`
`1 Nonproprietary Names
`BP: Mannitol
`JP: D-Mannitol
`PhEur: Mannitolum
`USP: Mannitol
`
`2 Synonyms
`Cordycepic acid; £421; manna sugar; D-mannite; mannite;
`Mannogem; Pearlitol.
`
`3 Chemical Name and CAS Registry Number
`D-Mannitol [69-65-8]
`
`4 Empirical Formula
`
`C6H1406
`
`Molecular Weight
`182.17
`
`5 Structural Formula
`
`HO---+--H
`
`HO---+--H
`
`H---+--OH
`
`H---+--OH
`
`6 Functional Category
`Sweetening agent; tablet and capsule diluent; tonicity agent;
`vehicle (bulking agent) for lyophilized preparations.
`
`7 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 (10-90% 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 applica(cid:173)
`tions,(2-6) for which the granular and spray-dried forms are
`available, or in wet granulations.(?) Granulations containing
`m~nnitol have the advantage of being dried easily. Specific
`tablet applications include antacid preparations, glyceryl trini(cid:173)
`trate 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, sweet(cid:173)
`ness, and 'mouth feel'_(s, 9)
`In lyophilized preparations, mannitol (20-90% w/w) has
`been included as a carrier to produce a stiff, homogene
`
`that imgroves the appearance of the lyophilized plug in a
`vial.(10- ?) 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 ( < 7%
`w/v). It has been suggested as a plasticizer in soft-gelatin
`capsules, as a component of sustained-release tablet formula(cid:173)
`tions, (JS) and as a carrier in dry powder inhalers.(1 9
`) It is also
`used in food applications as a bulking agent.
`Therapeutically, mannitol administered parenterally is used
`as an osmotic diuretic, as a diagnostic agent for kidney func(cid:173)
`tion, 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 GI tract, but in large doses it
`can cause osmotic diarrhea; see Section 14.
`
`8 Description
`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. Manni(cid:173)
`tol shows polymorphism. (20)
`
`9 Pharmacopeial Specifications
`See Table I.
`
`SEM: 1
`Excipient: M annitol
`Manufacturer: Merck
`Magnification: 50 x
`Voltage: 3.5 kV
`
`MERCK REM -Team
`
`373
`
` PFIZER, INC. v. NOVO NORDISK A/S - IPR2020-01252, Ex. 1023, p. 12 of 24
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