Chlorobutanol

(BAN, rINN)
Chlorobutanol Chemical formula
Synonyms: Acetone-Chloroforme; Alcohol Trichlorisobutylicus; Chlorbutanol; Chlorbutanolum; Chlorbutol; Chloretone; Chlorobutanolis; Chlorobutanolum; Clorobutanol; Klooributanoli; Klorbutanol; Klorobutanol; Trichlorbutanolum. 1,1,1-Trichloro-2-methylpropan-2-ol.
Cyrillic synonym: Хлоробутанол.

💊 Chemical information

Chemical formula: C4H7Cl3O = 177.5.
CAS — 57-15-8 (anhydrous chlorobutanol); 6001-64-5 ATC — A04AD04.
ATC Vet — QA04AD04.

Pharmacopoeias.

Eur., Int., and USNF allow either the anhydrous form or the hemihydrate; Eur. includes them as separate monographs. Chin. specifies the hemihydrate. Jpn permits up to 6% of water.

Ph. Eur. 6.2 (Chlorobutanol Hemihydrate; Chlorobutanol BP 2008). A white or almost white, crystalline powder or colourless crystals. It sublimes readily. M.p. about 78°. Slightly soluble in water; very soluble in alcohol; soluble in glycerol (85%). Store in airtight containers.

Ph. Eur. 6.2 (Chlorobutanol, Anhydrous). A white or almost white, crystalline powder or colourless crystals. It sublimes readily. M.p. about 95°. Slightly soluble in water; very soluble in alcohol; soluble in glycerol (85%). Store in airtight containers.

USNF 26

(Chlorobutanol). It is anhydrous or contains not more than one-half molecule of water of hydration. Colourless or white crystals with a characteristic, somewhat camphoraceous odour. M.p. about 76° for the hemihydrate and about 95° for the anhydrous form. Soluble 1 in 125 of water, 1 in 1 of alcohol, and 1 in 10 of glycerol; freely soluble in chloroform, in ether, and in volatile oils. Store in airtight containers.

Incompatibility and stability.

The activity of chlorobutanol can be adversely affected by the presence of other compounds as well as by the packaging material. There may be sorption onto substances like magnesium trisilicate, bentonite, carmellose, 1 polyethylene, 2,3 or polyhydroxy-ethylmethacrylate that has been used in soft contact lenses. 4 Increasing heat 2,3 or pH 5,6 can reduce stability and activity. 1. Yousef RT, et al. Effect of some pharmaceutical materials on the bactericidal activities of preservatives. Can J Pharm Sci 1973; 8: 54–6. 2. Friesen WT, Plein EM. The antibacterial stability of chlorobutanol stored in polyethylene bottles. Am J Hosp Pharm 1971; 28: 507–12. 3. Holdsworth DG, et al. Fate of chlorbutol during storage in polyethylene dropper containers and simulated patient use. J Clin Hosp Pharm 1984; 9: 29–39. 4. Richardson NE, et al. The interaction of preservatives with polyhydroxy-ethylmethacrylate (polyHEMA). J Pharm Pharmacol 1978; 30: 469–75. 5. Nair AD, Lach JL. The kinetics of degradation of chlorobutanol. J Am Pharm Assoc (Sci) 1959; 48: 390–5. 6. Patwa NV, Huyck CL. Stability of chlorobutanol. J Am Pharm Assoc 1966; NS6: 372–3.

💊 Adverse Effects

Acute poisoning with chlorobutanol may produce CNS depression with weakness, loss of consciousness, and depressed respiration. Delayed (type IV) hypersensitivity reactions have been reported rarely.
1. Nordt SP. Chlorobutanol toxicity. Ann Pharmacother 1996; 30: 1179–80.

Effects on the cardiovascular system.

Rapid falls in arterial blood pressure were observed after injections of heparin containing chlorobutanol in patients undergoing coronary bypass.1 No fall in blood pressure was seen in patients who received preservative-free heparin injection.
1. Bowler GMR, et al. Sharp fall in blood pressure after injection of heparin containing chlorbutol. Lancet 1986; i: 848–9.

Effects on mental function.

The sedative effects of chlorobutanol have been reported to be a problem in a patient dependent on large doses (0.9 to 1.5 g daily with salicylamide 1.8 to 3.0 g daily)1 and in another patient given high doses of morphine in an infusion preserved with chlorobutanol.2
1. Borody T, et al. Chlorbutol toxicity and dependence. Med J Aust 1979; i: 288
2. DeChristoforo R, et al. High-dose morphine infusion complicated by chlorobutanol-induced somnolence. Ann Intern Med 1983; 98: 335–6.

Hypersensitivity.

A delayed, cellular type of hypersensitivity reaction to chlorobutanol used to preserve heparin injection after subcutaneous injection has been reported.1 Pruritus from intranasal desmopressin has been attributed to the chlorobutanol preservative.2
1. Dux S, et al. Hypersensitivity reaction to chlorbutanol-preserved heparin. Lancet 1981; i: 149
2. Itabashi A, et al. Hypersensitivity to chlorobutanol in DDAVP solution. Lancet 1982; i: 108.

💊 Uses and Administration

Chlorobutanol has antibacterial and antifungal properties and it is used at a concentration of 0.5% as a preservative in injections and in eye drops as well as cosmetics. Chlorobutanol has been used as a mild sedative and local analgesic but other compounds are preferred. It has been used in preparations for inflammatory and painful conditions of the ear and oropharynx.

💊 Preparations

Proprietary Preparations

Fr.: Optrex; Port.: Vizoptal†. Multi-ingredient: Arg.: Eludril; Otocalmia; Austral.: Cerumol; Austria: Aleot; Belg.: Eludril; Givalex; Prurisedine; Braz.: Auritricin; Lavolho†; Canad.: Cerumol; Fr.: Alodont; Balsamorhinol; Eludril; Givalex; Ger.: Givalex†; Hong Kong: Fungifax†; India: Andre; Clearwax; Waxolve; Irl.: Cerumol; Karvol; Israel: Cepadont; Cerumol; Dentin; Karvol; Pitrisan; Ital.: Fialetta Odontalgica Dr Knapp; Odontalgiche (Dentali)†; Malaysia: Cerumol; NZ: Frador; Port.: Eludril; Otoceril; Rus.: Eludril (Элюдрил); S.Afr.: Aurone Forte; Cerumol; Chamberlains Traditional Colic Remedy; Karvol; Singapore: Cerumol; Eludril; Karvol; Spain: Eludril; Otocerum; Switz.: Alodont†; Cerumenol; Eludril; Thai.: Opplin†; Optal; Optic; Turk.: Disinol; UK: Cerumol; Cetanorm; DDD; Dermidex; Eludril; Frador; Karvol; Monphytol†; USA: Outgro.
Published December 12, 2018.