L-Menthol

Category

Flavoring agent

Molecular Formula

C10H20O

Molecular Weight

156.27

Grade

Pharmceutical Excipients

Description

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.

UNII

BZ1R15MTK7

Chemical Name

(1RS, 2RS, 5RS)-(±)-5-Methyl-2-(1-methylethyl)cyclohexanol

CAS Number

15356-70-4

Synonyms

Hexahydrothymol; 2-isopropyl-5-methylcyclohexanol; 4-isopropyl-1-methylcyclohexan-3-ol; 3-p-menthanol

Administration route

Dental, inhalations, oral; topical

Dosage Form

Dental preparations, inhalations, oral aerosols, capsules, solutions, suspensions, syrups, and tablets; also topical preparations

Stability and Storage Conditions

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℃, since it sublimes readily.

Source and Preparation

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, menthol 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.

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

Incompatibilities

Incompatible with: butylchloral hydrate; camphor; chloral hydrate; chromium trioxide; b-naphthol; phenol; potassium permanganate; pyrogallol; resorcinol; and thymol.