DL-Menthol

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.

The Uses of DL-Menthol

Labelled Menthol. Used for oral gel patch or film containing herb extracts or Chinese medicine, fruit extract, spearmint, and menthol for smoking cessation.

The Uses of DL-Menthol

menthol is a fragrance. It is also said to be anti-septic, cooling, refreshing, and a blood-circulation stimulant. Menthol gives the skin a “cool” feeling after use. It constitutes almost 50 percent of peppermint oil but can also be synthetically produced through the hydrogenation of thymol. It is non-toxic in low doses, but in high concentrations it can be irritating to the skin, especially the mucous membranes.

The Uses of DL-Menthol

Menthol is used in confectionery, perfumery, cough drops, cigarettes, liqueurs, etc.; topical antipruritic; local anesthetic; gastric sedative.

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.

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.

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

Metabolism

Not Available

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.