Menthol

(BAN, rINN)
Menthol Chemical formula

💊 Chemical information

Hexahydrothymol; Mentholum; Mentol; Mentoli; Mentolis. pMenthan-3-ol; 2-Isopropyl-5-methylcyclohexanol.
Chemical formula: C10H20O = 156.3.
CAS — 1490-04-6 (menthol); 15356-60-2 ((+)-menthol); 2216-51-5 (( )-menthol); 89-78-1(( )-menthol).

Description.

Menthol is either the laevo-isomer, levomenthol (BAN, rINN), or a racemic mixture, racementhol (BAN, rINN). The laevo-isomer may be obtained from the volatile oils of various species of Mentha (Labiatae) or it may be prepared synthetically.

Pharmacopoeias.

In Chin., Eur., Jpn, US, and Viet. Eur. and Jpn have separate monographs for laevo-menthol (levomenthol) and racemic menthol (racementhol).

Ph. Eur. 6.2 (Levomenthol). It occurs as colourless, acicular or prismatic shiny crystals. M.p. about 43°. Practically insoluble in water; very soluble in alcohol and in petroleum spirit; freely soluble in fatty oils and in liquid paraffin; very slightly soluble in glycerol.

Ph. Eur. 6.2 (Menthol, Racemic; Racementhol BP 2008). It occurs as colourless, acicular or prismatic shiny crystals or as a free-flowing or agglomerated crystalline powder. M.p. about 34°. Practically insoluble in water; very soluble in alcohol and in petroleum spirit; freely soluble in fatty oils and in liquid paraffin; very slightly soluble in glycerol.

USP 31

(Menthol). An alcohol obtained from diverse mint oils or prepared synthetically. It may be laevorotatory (l-menthol), from natural or synthetic sources, or racemic (dl-menthol). It occurs as colourless, hexagonal crystals, usually needle-like, or in fused masses, or crystalline powder. Has a pleasant, peppermintlike odour. M.p. of l-menthol 41° to 44°. Slightly soluble in water; very soluble in alcohol, in chloroform, in ether, and in petroleum spirit; freely soluble in glacial acetic acid, in fixed and volatile oils, and in liquid paraffin. Store in airtight containers preferably at a temperature of 15° to 30°.

Compounding.

A liquid or soft mass is formed when menthol is triturated with camphor, cloral hydrate, phenol, and many other substances. Methods of preparing menthol 1% w/w in aqueous cream BP and the stability of the resultant product have been discussed. 1 1. Cable C. The preparation of menthol (1 per cent w/w) in aqueous cream BP. Pharm J 2005; 274: 469.

💊 Adverse Effects, Treatment, and Precautions

Menthol may give rise to hypersensitivity reactions including contact dermatitis. Ingestion of significant quantities of menthol is reported to cause symptoms similar to those seen after ingestion of camphor, including severe abdominal pain, nausea, vomiting, vertigo, ataxia, drowsiness, and coma; they may be managed similarly. There have been reports (below) of apnoea and instant collapse in infants after the local application of menthol to their nostrils.

Administration to infants.

Instillation of decongestant preparations containing menthol directly into the nostrils of infants and young children has resulted in acute respiratory distress with cyanosis1 and respiratory arrest,2 and must be avoided. In one case,1 nasal application was associated with concurrent chemical conjunctivitis.
1. Wyllie JP, Alexander FW. Nasal instillation of ‘Olbas Oil’ in an infant. Arch Dis Child 1994; 70: 357–8
2. Blake KD. Dangers of common cold treatments in children. Lancet 1993; 341: 640.

Effects on the nervous system.

Ataxia, confusion, euphoria, nystagmus, and diplopia developed in a 13-year-old boy following the inhalation of 5 mL of Olbas oil instead of the recommended few drops.1 It was considered probable that the menthol in the preparation was responsible for the symptoms; the amount of menthol inhaled was approximately 200 mg.
1. O’Mullane NM, et al. Adverse CNS effects of menthol-containing Olbas oil. Lancet 1982; i: 1121.

💊 Pharmacokinetics

After absorption, menthol is excreted in the urine and bile as a glucuronide.

Absorption.

The systemic absorption of camphor, menthol, and methyl salicylate from dermal patches containing all three ingredients has been studied.1 The absolute bioavailability of these compounds could not be determined from this study, but there did not appear to be any substantial systemic accumulation even after unrealistically high exposure for prolonged periods.
1. Martin D, et al. Dermal absorption of camphor, menthol, and methyl salicylate in humans. J Clin Pharmacol. 2004; 44: 1151–7.

💊 Uses and Administration

Menthol is chiefly used to relieve symptoms of bronchitis, sinusitis, and similar conditions. For this purpose it may be used as an inhalation, usually with benzoin or eucalyptus oil, as pastilles, or as an ointment with camphor and eucalyptus oil for application to the chest or nostrils (but see Adverse Effects above). However, as mentioned under the section on the management of cough, the use of menthol in inhalations is unlikely to provide any additional benefit. 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, or ointments in pruritus and urticaria. It has also been applied to the forehead, presumably as a counter-irritant, for the relief of headache. In small doses by mouth menthol has a carminative action.

Action.

It has been suggested that the apparent benefits of menthol in nasal congestion may be due to an effect on calcium channels of sensory nerves.1 This mechanism has also been implicated in its muscle relaxant action on the gastrointestinal tract when used as peppermint oil.
1. Anonymous. How does menthol work? Pharm J 1993; 251: 480.

💊 Preparations

BP 2008: Levomenthol Cream; Menthol and Benzoin Inhalation; USP 31: Benzocaine and Menthol Topical Aerosol; Menthol Lozenges; Tetracaine and Menthol Ointment.

Proprietary Preparations

Arg.: Flex-All; Rati Salil Ice; Robitussin Caramelos†; Austral.: Dencorub Arthritis Ice; Ice Gel; Vicks Throat Drops†; Vicks Vapodrops with Butter and Menthol; Braz.: Analgen†; Canad.: Absorbine Jr; Absorbine Jr Roll-on Ice; Absorbine Power Gel; Antiphlogistine Rub A-535 Ice; Bengay Ice†; Bentasil†; Certified Ice; Cough Drops; Cough Lozenges; Deep Cold; Fisherman’s Friend; Flex-All; Ice Gel Therapy; Ice Gel†; Meggezones†; Physiomenthol; Polar Ice; Soothing Ice Rub; Vicks Throat Drops; Chile: Friorub; Hielorub; Mentholatum Patch; Ger.: Klosterfrau Franzbranntwein Menthol; Nifint†; Hong Kong: Counterpain; India: Dolocide Plus; Indon.: Counterpain Cool; Malaysia: Menzza Ice; Mex.: Friocal†; NZ: Vicks Throat Drops; Vicks Vapodrops; Pol.: Deep Relief†; Migrenol; Port.: Vicks Vaporub; Singapore: Celatrac; Counterpain Cool; Spain: Prulit; Switz.: Perskindol Cool; Thai.: Centropain; Counterpain Cool; Painza Cool; Stopain; UK: Arjun; Deep Freeze Cold Gel; Dermacool; Happinose; Ice Cool Stress & Tension Relief; Meggezones; Quool; Vicks Vaposyrup for Tickly Coughs; USA: Absorbine Jr; Ben-Gay Patch; Ben-Gay Vanishing; Cepacol Sore Throat Post Nasal Drip; Extra Strength Vicks Cough Drops; Halls-Plus Maximum Strength; Icy Hot Back Pain Relief; Icy Hot Pop & Peel; Icy Hot Pro-Therapy; Kof-Eze; Mineral Freez Gel; N’ice; N’ice ’n Clear; Salonpas Aqua Patch; Sportscreme Ice; Therapeutic Mineral Ice; Therapy Ice; Vicks Cough Drops; Wonder Ice; Venez.: Dencorub Ice; Inquifric†.
Published May 08, 2019.