Glycerol

(rINN)
Glycerol Chemical formula
Synonyms: E422; Glicerin; Glicerol; Glicerolis; Gliserin; Gliserol; Glisin; Glycerin; Glycerine; Glycérol; Glycerolum; Glyseroli. Propane-1,2,3triol.
Cyrillic synonym: Глицерол.

💊 Chemical information

Chemical formula: C3H8O3 = 92.09.
CAS — 56-81-5.
ATC — A06AG04; A06AX01.
ATC Vet — QA06AG04; QA06AX01; QA16QA03.

Pharmacopoeias.

In Chin., Eur., Int., Jpn, US, and Viet. Eur. and Int. also include Glycerol (85 per cent).

Ph. Eur. 6.2

(Glycerol). A clear, colourless or almost colourless, very hygroscopic, syrupy liquid, unctuous to the touch. Miscible with water and with alcohol; slightly soluble in acetone; practically insoluble in fixed oils and in essential oils. Store in airtight containers.

USP 31

(Glycerin). A clear, colourless, hygroscopic, syrupy liquid. Has not more than a slight characteristic odour, which is neither harsh nor disagreeable. Miscible with water and with alcohol; insoluble in chloroform, in ether, and in fixed and volatile oils. Its solutions are neutral to litmus. Store in airtight containers.

Incompatibility.

Strong oxidising agents form explosive mixtures with glycerol. Black discoloration has been reported with glycerol and bismuth subnitrate or zinc oxide when exposed to light.

💊 Adverse Effects and Precautions

The adverse effects of glycerol are primarily due to its dehydrating action. When taken orally glycerol may cause headache, nausea, and vomiting; diarrhoea, thirst, dizziness, and mental confusion may occur less frequently. Cardiac arrhythmias have been reported. Glycerol increases plasma osmolality resulting in the withdrawal of water from the extravascular spaces. The consequent expansion of extracellular fluid, especially if sudden, can lead to circulatory overload, pulmonary oedema, and heart failure; glycerol must therefore be used with caution in patients at risk, such as those with hypervolaemia, cardiac failure, or renal disease. Severe dehydration can occur and glycerol should be used cautiously in dehydrated patients. Patients with diabetes mellitus may additionally develop hyperglycaemia and glycosuria after metabolism of glycerol. Nonketotic hyperosmolar hyperglycaemic coma is rare, but fatalities have been reported. Haemolysis, haemoglobinuria, and acute renal failure have also been associated with glycerol when given intravenously (see Raised Intracranial Pressure, below). Glycerol can cause irritation when given topically or rectally. A local anaesthetic may be used before application of glycerol to the cornea to reduce the likelihood of a painful response. For incompatibilities with glycerol, including the risk of explosive mixtures, see above.

Effects on the cardiovascular system.

A 73-year-old man, free of cardiac complaints but who had previously had an acute myocardial infarction, developed severe pulmonary oedema after use of glycerol orally for elevated intra-ocular pressure.1 The necessity for detailed cardiac evaluation before the use of oral glycerol was emphasised.
1. Almog Y, et al. Pulmonary edema as a complication of oral glycerol administration. Ann Ophthalmol 1986; 18: 38–9.

Effects on the ears.

A 56-year-old man given 100 mL of glycerol and 100 mL of sodium chloride 0.9% as part of a test for Ménière’s disease developed temporary hearing loss in the noninvolved ear. Two previous reports of deterioration in hearing associated with the glycerol test were reviewed by the author.1
1. Mattox DE, Goode RL. Temporary loss of hearing after a glycerin test. Arch Otolaryngol 1978; 104: 359–61.

Effects on the eyes.

Caution in applying glycerol to the cornea has been recommended. Studies in animals1 and in man2 have indicated that the topical application of glycerol to the eye can damage the endothelial cells of the cornea.
1. Sherrard ES. The corneal endothelium in vivo: its response to mild trauma. Exp Eye Res 1976; 22: 347–57
2. Goldberg MH, et al. The effects of topically applied glycerin on the human corneal endothelium. Cornea 1982; 1: 39–44.

Hyperosmolar nonketotic coma.

Hyperosmolar nonketotic coma has been associated with the oral use of glycerol1 and deaths have occurred.2 The most susceptible patients are maturity-onset elderly diabetics with acute or chronic disease predisposing to fluid deprivation, and in these patients oral glycerol may be best avoided.1 If glycerol is used in patients with predisposing conditions, adequate measures should be taken to recognise the development of hyperosmolar nonketotic hyperglycaemia and prevent dehydration.1,2
1. Oakley DE, Ellis PP. Glycerol and hyperosmolar nonketotic coma. Am J Ophthalmol 1976; 81: 469–72
2. Sears ES. Nonketotic hyperosmolar hyperglycemia during glycerol therapy for cerebral edema. Neurology 1976; 26: 89–94.

💊 Pharmacokinetics

Glycerol is readily absorbed from the gastrointestinal tract and undergoes extensive metabolism, mainly in the liver; it may be used in the synthesis of lipids, metabolised to glucose or glycogen, or oxidised to carbon dioxide and water. It may also be excreted in the urine unchanged.
1. Nahata MC, et al. Variations in glycerol kinetics in Reye’s syndrome. Clin Pharmacol Ther 1981; 29: 782–7
2. Heinemeyer G. Clinical pharmacokinetic considerations in the treatment of increased intracranial pressure. Clin Pharmacokinet 1987; 13: 1–25.

💊 Uses and Administration

Glycerol is an osmotic dehydrating agent with hygroscopic and lubricating properties. When given orally or parenterally, glycerol increases the plasma osmolality, resulting in the movement of water by osmosis from the extravascular spaces into the plasma. Glycerol is given by mouth for the short-term reduction of vitreous volume and intra-ocular pressure before and after ophthalmic surgery, and as an adjunct in the management of acute glaucoma. Its onset of action is rapid, with a maximal reduction in intra-ocular pressure occurring about 1 to 1 ⁄ hours after a dose; the duration of action is about 5 hours. The usual initial dose of glycerol is 1 to 1.8 g/kg given as a 50% solution. There can be problems of palatability when glycerol solutions are given orally; chilling or flavouring the solutions may help. Glycerol may be applied topically to reduce corneal oedema, but as the effect is only transient its use is largely limited to an adjunct in eye examination and diagnosis. Glycerol eye drops can be painful on instillation and use of a local anaesthetic beforehand has been recommended. Glycerol has also been given orally or intravenously to reduce intracranial pressure (see below). Glycerol may be used rectally as suppositories or a solution in single doses to promote faecal evacuation in the management of constipation. It usually acts within 15 to 30 minutes. Glycerol is commonly classified as an osmotic laxative but may act additionally or alternatively through its local irritant effects; it may also have lubricating and faecal softening actions. Glycerol is used as a demulcent in cough preparations. Glycerol has many applications in pharmaceutical formulation; these include its use as a vehicle and solvent, as a sweetening agent, as a preservative in some liquid medications, as a plasticiser in tablet film-coating, and as a tonicity adjuster. It is often included in topical preparations such as eye drops, creams, and lotions as a lubricant and also for its moisturising properties since, when absorbed, its hygroscopic action can enhance moisture retention. Ear drops for the removal of ear wax often contain glycerol as a lubricating and softening agent. Glycerol is also used as a cryoprotectant in cryopreservation.

Diagnosis of Ménière’s disease.

Glycerol has been used1 in the diagnosis of Ménière’s disease to distinguish potentially reversible cochlear dysfunction from the relatively irreversible pathology of advanced disease, or to predict the results of endolymphatic sac surgery. Glycerol is given by mouth to reduce the endolymphatic fluid volume and pressure and any transient improvement in hearing is measured. However, the adverse effects of glycerol such as headache, nausea, and vomiting can be a problem and the test has been reported to have low sensitivity and to give false-positive results. See also under Effects on the Ears, above.
1. Skalabrin TA, Mangham CA. Analysis of the glycerin test for Meniere’s disease. Otolaryngol Head Neck Surg 1987; 96: 282–8.

Raised intracranial pressure.

Glycerol has been given intravenously or by mouth for its osmotic diuretic effect to reduce cerebral oedema and hence decrease the intracranial pressure. It is also reported to be able to increase blood flow to areas of brain ischaemia. It has been used in a variety of clinical conditions1 including cerebral infarction or stroke,2 Reye’s syndrome,3 and meningitis.4,5 It has been postulated5 that glycerol’s beneficial action in preventing the neurological sequelae in bacterial meningitis is due to its effects in increasing cerebral plasma osmolality, which reduces cerebral oedema and enhances cerebral circulation by reducing the excretion of cerebrospinal fluid, and that this may be more important than the decrease in intracranial pressure induced by osmotic diuresis. Glycerol has been reported to be ineffective in hepatic coma.6 Some patients have had serious adverse effects including haemolysis, haemoglobinuria, and renal failure.7,8
1. Frank MSB, et al. Glycerol: a review of its pharmacology, pharmacokinetics, adverse reactions, and clinical use. Pharmacotherapy 1981; 1: 147–60
2. Righetti E, et al. Glycerol for acute stroke. Available in The Cochrane Database of Systematic Reviews; Issu
2. Chichester: John Wiley; 2004 (accessed 23/05/06)
3. Nahata MC, et al. Variations in glycerol kinetics in Reye’s syndrome. Clin Pharmacol Ther 1981; 29: 782–7
4. Kilpi T, et al. Oral glycerol and intravenous dexamethasone in preventing neurologic and audiologic sequelae of childhood bacterial meningitis. Pediatr Infect Dis J 1995; 14: 270–8
5. Peltola H, et al. Adjuvant glycerol and/or dexamethasone to improve the outcomes of childhood bacterial meningitis: a prospective, randomized, double-blind, placebo-controlled trial. Clin Infect Dis 2007; 45: 1277–86
6. Record CO, et al. Glycerol therapy for cerebral oedema complicating fulminant hepatic failure. BMJ 1975; ii: 540
7. Hägnevik K, et al. Glycerol-induced haemolysis with haemoglobinuria and acute renal failure: report of three cases. Lancet 1974; i: 75–7
8. Welch KMA, et al. Glycerol-induced haemolysis. Lancet 1974; i: 416–17.

Trigeminal neuralgia.

Selective destruction of pain-bearing nerves is reserved for patients who do not respond to conventional drug therapy for trigeminal neuralgia. This may be achieved by the instillation of glycerol among the trigeminal rootlets (percutaneous retrogasserian glycerol rhizolysis).1-5 The efficacy and safety of this procedure have been debated,1,4 but some centres report good long-term results in the majority of patients.5 It has been suggested that variations in viscosity and osmolality may influence results.2
1. Sweet WH. The treatment of trigeminal neuralgia (tic douloureux). N Engl J Med 1986; 315: 174–7
2. Waltz TA, Copeland BR. Treatment of trigeminal neuralgia. N Engl J Med 1987; 316: 693
3. Young RF. Glycerol rhizolysis for treatment of trigeminal neuralgia. J Neurosurg 1988; 69: 39–45
4. Burchiel KJ. Percutaneous retrogasserian glycerol rhizolysis in the management of trigeminal neuralgia. J Neurosurg 1988; 69: 361–6
5. Jho H-D, Lunsford LD. Percutaneous retrogasserian glycerol rhizotomy: current technique and results. Neurosurg Clin N Am 1997; 8: 63–74.

💊 Preparations

BP 2008: Glycerol Eye Drops; Glycerol Suppositories; Phenol and Glycerol Injection; USP 31: Calamine Topical Suspension; Glycerin Ophthalmic Solution; Glycerin Oral Solution; Glycerin Suppositories.

Proprietary Preparations

Arg.: Refenax Lagrimas; Vixorfit; Austral.: Bausch & Lomb Computer Eye Drops; Braz.: Glicel†; Chile: Fleet Babylax; Fr.: Bebegel; Ger.: Glycerosteril; Glycilax; Milax; Nene-Lax; Otodolor Soft; Gr.: Glicerolo microclismi†; Glycare; Microclismata; Hong Kong: Computer Eye Drops; Fleet Babylax; Glyceol; Wet Stuff; Irl.: Babylax; Israel: Minilax†; Ital.: Verolax; Zetalax; Jpn: Glyceol; Malaysia: Egozite Protective Baby Lotion; Fleet Babylax; ZenCare; Mex.: Estrin; Fleet Adulto; Fleet Infantil; Fleet Pedialax; Micronovag; Neutrobar; PC; Supositorios Senosiain; Philipp.: Babylax; Computer Eye Drops; Novas; United Home Glydolax; Port.: Bebegel; Dolorecto; Glycelax; Microcel; Rectiole; Verolax; S.Afr.: Regard; Singapore: Acnederm Wash; Fleet Babylax†; Spain: Adulax; Comosup; Gely; Glicerotens; Paidolax; Supo Gliz; Verolax; Vitrosups; Swed.: Miniderm; Switz.: Bulboid; Practomil; Thai.: Glyceol; Glycerosteril†; UAE: Laxolyne; UK: Benylin Tickly Coughs; Boots Cough Syrup 3 Months Plus; CalCough Tickly; Neutrogena Norwegian Formula Dermatological Cream; Nirolex Dry Cough; Senokot Direct Relief; Tixylix Baby Syrup; USA: Colace Infant/Child; Computer Eye Drops†; Eye-Lube-A; Fleet Babylax; Listermint Arctic Mint Mouthwash; Osmoglyn; Sani-Supp; Venez.: Fleet Babylax. Multi-ingredient: Arg.: Irix Lagrimas; Keracnyl; Micronema; Sincerum Dry; Skleremo†; Ureadin Facial; Visine Lagrimas; Austral.: Aci-Jel†; Anusol; Auralgan; Egopsoryl TA; Hamilton Body Lotion†; Hamilton Cleansing Lotion†; Hamilton Dry Skin; Magnoplasm; SM-33; Soothe’n Heal; Visine True Tears†; Austria: Lacrisic; Belg.: Aloplastine; Laxavit; Braz.: Bluderm†; Dermamina; Effidrate†; Estomafitino†; Pasta d’Agua†; Trisorb; Varikromo†; Canad.: Agarol Plain; Auralgan; Bronchex†; Epi-Lyt; Lubriderm Advanced Moisture†; Moisture Drops†; Rhinedrine Moisturizing†; Swim-Ear†; Tears Naturale Forte; Tucks; Chile: Acnoxyl Jabon Liquido; Agarol; Cicapost; Nasivin; Ureadin Rx DB; Ureadin Rx RD; Denm.: Analka; Glyoktyl; Pectyl; Fr.: Aloplastine; Charlieu Topicrem; Derm’Intim; Dexeryl; Eryange†; Ictyane; Ictyane HD; Kertyol-S; Pharmatex; PSO; Rectopanbiline; Saugella; Scleremo; Septiane; Taido; Ger.: GeloBacin; Lacrisic; Lubrikano; Norgalax Miniklistier; Zinksalbe; Hong Kong: Acnederm; Acnederm Wash; Aderma Dermalibour†; Aderma Exomega†; Apaisac; Baby Cough with Antihistamine; Ego Skin Cream; Egopsoryl TA; Gly Thymol; Moisture Eyes; Tears Naturale Forte; Visine for Contacts; India: Neotomic; Otogesic; Indon.: Isotic Tearin; Laxadine; Irl.: Micolette; Israel: Dryears; Kamil Blue; Microlet; Taro Gel; Ital.: Dropyal; Evasen Dischetti; Evasen Liquido; Glicerolax; Microclismi Marco Viti; Microclismi Sella; Naturalass; Novilax; Rinogutt Atlantic; Salviette H; Solecin; Malaysia: Ego Skin Cream; Lorasil Feminine Hygeine†; Mex.: Maxibiloba; Moisture Eyes; Nasalub; Nutegen G†; Nutrasorb; NZ: Aci-Jel†; Auralgan; Ego Skin Cream; Karicare Breast and Body Cream†; Karicare Ointment†; Lemsip Dry Cough†; Rosken Skin Repair; Silic; Philipp.: Lactaderm; Moisture Eyes; pHCare; Visine Refresh; Pol.: Rektiolax; Unibasis; Port.: Antiacneicos Niacex†; Cicapost; Dagragel; Hidratante VG; Lubrificante Anestesico; Multi-Mam Compressas†; Nutraisdin; Ureadin Facial; Ureadin Maos; S.Afr.: Auralyt; Caloplast; Moisture Drops†; Singapore: Acnederm; Ego Skin Cream; Egozite Protective Baby Lotion†; Topicrem; Trop ex; Switz.: Lacrycon; Neo-Decongestine; Realderm; Thai.: Baby Cough Syrup Atlantic; Baby Cough with Antihistamine; Turk.: Gleitgelen; Kalmosan; Kansilak; Libalaks; Sabalax; UK: Allens Junior Cough; Asonor; Beehive Balsam; Earex Plus; Honey & Molasses; Imuderm; Jackson’s Lemon Linctus; Jackson’s Troublesome Coughs; Lemsip Cough & Cold Dry Cough; Lockets; Lockets Medicated Linctus; Meltus Honey & Lemon; Micolette; Relaxit; Swim-Ear; USA: Allergen; Astroglide; Auralgan; Cetaklenz; Clearasil Antibacterial; Collyrium Fresh†; Entertainer’s Secret; Epi-Lyt; Formulation R; Hemorid For Women; Maxilube; Moisture Drops; N’ice; Numzit†; Preparation H; Refresh Dry Eye Therapy; Summers Eve Anti-Itch; Surgel; SwimEar; Therevac Plus; Therevac SB; Trimo-San; Tucks; Visine Pure Tears; Visine Te a r s ; Venez.: Audocaina†.
Published May 08, 2019.