Chemical Properties
colourless crystals
Chemical Properties
Racemic menthol is a mixture of equal parts of the (1R,2S,5R)- and
(1S,2R,5S)-isomers of menthol. It is a free-flowing or agglomerated
crystalline powder, or colorless, prismatic, or acicular shiny crystals,
or hexagonal or fused masses with a strong characteristic odor and
taste. The crystalline form may change with time owing to
sublimation within a closed vessel. The USP 32 specifies that
menthol may be either naturally occurring l-menthol or syntheti-cally prepared racemic or dl-menthol. However, the JP XV and
PhEur 6.0, along with other pharmacopeias, include two separate
monographs for racemic and l-menthol.
Definition
A white crystalline terpenealcohol, C10H19OH; r.d. 0.89;m.p. 42°C; b.p. 103–104°C. It has aminty taste and is found in certainessential oils (e.g. peppermint) andused as a flavouring.
Definition
ChEBI: Any secondary alcohol that is one of the eight possible diastereoisomers of 5-methyl-2-(propan-2-yl)cyclohexan-1-ol.
Production Methods
Menthol occurs widely in nature as l-menthol and is the principal
component of peppermint and cornmint oils obtained from the
Mentha piperita and Mentha arvensis species. Commercially, lmenthol
is mainly produced by extraction from these volatile oils. It
may also be prepared by partial or total synthetic methods.
Racemic menthol is prepared synthetically via a number of
routes, e.g. by hydrogenation of thymol.
Brand name
Fisherman’s Friend
Lozenges (Bristol-Myers Products); Therapeutic Mineral
Ice (Bristol-Myers Products).
Pharmaceutical Applications
Menthol is widely used in pharmaceuticals, confectionery, and
toiletry products as a flavoring agent or odor enhancer. In addition
to its characteristic peppermint flavor, l-menthol, which occurs
naturally, also exerts a cooling or refreshing sensation that is
exploited in many topical preparations. Unlike mannitol, which
exerts a similar effect due to a negative heat of solution, l-menthol
interacts directly with the body’s coldness receptors. d-Menthol has
no cooling effect, while racemic menthol exerts an effect approximately
half that of l-menthol.
When used to flavor tablets, menthol is generally dissolved in
ethanol (95%) and sprayed onto tablet granules and not used as a
solid excipient.
Menthol has been investigated as a skin-penetration enhancer
and is also used in perfumery, tobacco products, chewing gum and
as a therapeutic agent. When applied to the skin, menthol dilates the
blood vessels, causing a sensation of coldness followed by an
analgesic effect. It relieves itching and is used in creams, lotions, and
ointments. When administered orally in small doses menthol has a
carminative action.
Safety
Almost all toxicological data for menthol relate to its use as a
therapeutic agent rather than as an excipient. Inhalation or
ingestion of large quantities can result in serious adverse reactions
such as ataxia and CNS depression,hypersensitivity reactions,
severe abdominal pain, nausea, vomiting, vertigo, drowsiness, and
coma.Although menthol is essentially nonirritant there have been
some reports of hypersensitivity following topical application.
In a Polish study approximately 1% of individuals were determined
as being sensitive to menthol.There have been reports of apnea
and instant collapse in infants after the local application of menthol
to their nostrils.
The WHO has set an acceptable daily intake of menthol at up to
0.4 mg/kg body-weight.
LD50 (rat, IM): 10.0 g/kg
LD50 (rat, oral): 3.18 g/kg
storage
A formulation containing menthol 1% w/w in aqueous cream has
been reported to be stable for up to 18 months when stored at room
temperature.
Menthol should be stored in a well-closed container at a
temperature not exceeding 25°C, since it sublimes readily.
Incompatibilities
Incompatible with: butylchloral hydrate; camphor; chloral hydrate;
chromium trioxide; b-naphthol; phenol; potassium permanganate;
pyrogallol; resorcinol; and thymol.
Regulatory Status
Included in the FDA Inactive Ingredients Database (dental
preparations, inhalations, oral aerosols, capsules, solutions, suspensions,
syrups, and tablets; also topical preparations). Included in
nonparenteral medicines licensed in the UK. Accepted for use in
foods and confectionery as a flavoring agent of natural origin.
Included in the Canadian List of Acceptable Non-medicinal
Ingredients.
