8/13/2019 Menthol Ex

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Applications in Pharmaceutical Formulation orTechnologyMenthol is widely used in pharmaceuticals, confectionery, andtoiletry products as a flavoring agent or odor enhancer. In additionto its characteristic peppermint flavor, l-menthol, which occursnaturally, also exerts a cooling or refreshing sensation that isexploited in many topical preparations. Unlike mannitol, whichexerts a similar effect due to a negative heat of solution, l-mentholinteracts directly with the bodys coldness receptors. d-Menthol hasno cooling effect, while racemic menthol exerts an effect approximatelyhalf that of l-menthol.When used to flavor tablets, menthol is generally dissolved inethanol (95%) and sprayed onto tablet granules and not used as asolid excipient.Menthol has been investigated as a skin-penetration enhancerand is also used in perfumery, tobacco products, chewing gum andas a therapeutic agent. When applied to the skin, menthol dilates theblood vessels, causing a sensation of coldness followed by ananalgesic effect. It relieves itching and is used in creams, lotions, andointments. When administered orally in small doses menthol has acarminative action.IncompatibilitiesIncompatible with: butylchloral hydrate; camphor; chloral hydrate;chromium trioxide; b-naphthol; phenol; potassium permanganate;

pyrogallol; resorcinol; and thymol.13 Method of ManufactureMenthol occurs widely in nature as l-menthol and is the principalcomponent of peppermint and cornmint oils obtained from theMentha piperita and Mentha arvensis species. Commercially, lmentholis mainly produced by extraction from these volatile oils. Itmay also be prepared by partial or total synthetic methods.Racemic menthol is prepared synthetically via a number ofroutes, e.g. by hydrogenation of thymol.14 SafetyAlmost all toxicological data for menthol relate to its use as atherapeutic agent rather than as an excipient. Inhalation oringestion of large quantities can result in serious adverse reactions

such as ataxia(2) and CNS depression,(3) hypersensitivity reactions,severe abdominal pain, nausea, vomiting, vertigo, drowsiness, andcoma.(4) Although menthol is essentially nonirritant there have beensome reports of hypersensitivity following topical application.(5,6)In a Polish study approximately 1% of individuals were determinedas being sensitive to menthol.(7) There have been reports of apneaand instant collapse in infants after the local application of mentholto their nostrils.(4)The WHO has set an acceptable daily intake of menthol at up to0.4 mg/kg body-weight.(8)LD50 (rat, IM): 10.0 g/kg(9)LD50 (rat, oral): 3.18 g/kgHandling Precautions

May be harmful by inhalation or ingestion in large quantities; maybe irritant to the skin, eyes, and mucous membranes. Observenormal precautions appropriate to the circumstances and quantityof material handled. Eye protection, chemical resistant gloves, andrespirators are recommended.Avoid prolonged or repeated exposure.