 Docusate sodium | |
| Clinical data | |
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| Trade names | Colace, Ex-Lax Stool Softener, others |
| Other names | Dioctyl sulfosuccinate |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a601113 |
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| Routes of administration | By mouth,rectal |
| Drug class | Stool softener |
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| Pharmacokinetic data | |
| Onset of action | 12 hrs to 5 days[1] |
| Duration of action | 3 days[1] |
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| E number | E480(thickeners, ...) |
| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.008.553 |
| Chemical and physical data | |
| Formula | C20H37O7S |
| Molar mass | 421.57 g·mol−1 |
| 3D model (JSmol) |
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| Density | 1.1 g/cm3 |
| Melting point | 153 to 157 °C (307 to 315 °F) 173-179 °C |
| Solubility in water | 1 in 70 parts mg/mL (20 °C) |
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Docusate is the common chemical and pharmaceutical name of theanionbis(2-ethylhexyl) sulfosuccinate, also commonly calleddioctyl sulfosuccinate (DOSS).[2][3][4]
Salts of this anion, especiallydocusate sodium, are widely used inmedicine as an emollientlaxative and asstool softeners, by mouth or rectally.[1] Some studies state that docusate is not more effective than aplacebo for improving constipation.[5][6][7][8] Other docusate salts with medical use include those ofcalcium andpotassium.[9][1][2] Docusate salts are also used asfood additives,emulsifiers,dispersants, andwetting agents, among other uses.[10]
It is on theWorld Health Organization's List of Essential Medicines.[11] In 2023, it was the 148th most commonly prescribed medication in the United States, with more than 3 million prescriptions.[12][13] In 2023, the combination withsenna was the 242nd most commonly prescribed medication in the United States, with more than 1 million prescriptions.[12][14]
Sodium docusate was patented in 1937 by Coleman R. Caryl and Alphons O. Jaeger forAmerican Cyanamid,[3] which commercialized it for many years as adetergent under the brand nameAerosol OT.
Its use for the treatment of constipation was first proposed in 1955 byJames L. Wilson andDavid G. Dickinson,[4] and quickly popularized under the nameDoxinate.[15]
The main medical use of docusate sodium is to treatconstipation, acting as a laxative and stool softener. In painfulanorectal conditions such ashemorrhoid andanal fissures, it can help avoid pain caused by straining during bowel movements.[citation needed]
When administered by mouth, a bowel movement often occurs in 1 to 3 days,[1] while rectal use may be effective within 20 minutes.[16]
Sodium docusate is sometimes used as a stool softener for children.[1]
However, its effectiveness for constipation is poorly supported by evidence.[5][6] Multiple studies have found docusate to be no more effective than aplacebo for improving constipation.[5][6][7][8] Others have found it to be less useful for the treatment of chronic constipation thanpsyllium.[8][17][18]
The medication may be given to people who are receivingopioid medication, although prolonged use may cause irritation of the gastrointestinal tract and there is no high-quality evidence supporting its use.[8][18]
Docusate sodium, when used with ear syringing, may help withearwax removal, particularly in the case of impaction.[19]
Sodium docusate is also used as alubricant in the production oftablets and as anemulsifier in topical preparations and othersuspensions.[20]
Docusate sodium is approved and recommended as safe duringpregnancy andbreastfeeding.[21][22]
Docusate is not recommended in people withappendicitis,acute abdomen, orileus.[18]
When taken by mouth it should be ingested with plenty of water.
Side effects are uncommon and typically mild,[1] and may includestomach pain,abdominal cramps ordiarrhea,[1] Efficacy decreases with long-term use, and may cause poor bowel function.[9]
Serious allergic reactions may occur with the drug. The most severe side effect of docusate, although very rare, is rectal bleeding.[23]
Docusate might increase the resorption of other drugs, for example,dantron (1,8-dihydroxyanthraquinone).[18]
Docusate is ananionic surfactant, which works by reducing the surface tension of thestool, allowing more intestinal water and fat to combine with the stool.[24][9][25] This decreases the strain and discomfort associated withconstipation.[24]
It does not stay in the gastrointestinal tract but is absorbed into the bloodstream and excreted via thegallbladder[18] after undergoing extensive metabolism.
In the U.S., docusate sodium for pharmaceutical use is available under multiple brand names: Aqualax, Calube, Colace, Colace Micro-Enema, Correctol Softgel Extra Gentle, DC-240, Dialose, Diocto, Dioctocal, Dioctosoftez, Dioctyn, Dionex, Doc-Q-Lace, Docu Soft, Docucal, Doculax, Docusoft S, DOK, DOS, Doss-Relief, DSS, Dulcolax - Stool Softener (not to be confused with another drug marketed under the Dulcolax brand,bisacodyl, which is a stimulant laxative), Ex-Lax Stool Softener, Fleet Sof-Lax, Genasoft, Kasof, Laxa-basic, Modane Soft, Octycine-100, Pedia-Lax, Preferred Plus Pharmacy Stool Softener, Regulax SS, Sulfalax Calcium, Sur-Q-Lax, Surfak Stool Softener, and Therevac-SB. Generic preparations are also available.
In the UK, dioctyl sodium sulfosuccinate is sold under the brand names Docusol (Typharm Ltd) and DulcoEase (Boehringer Ingelheim).
In Australia, dioctyl sodium sulfosuccinate is sold as Coloxyl and Coloxyl withsenna.
In India, preparations include Laxatin by Alembic, Doslax by Raptakos Laboratories, Cellubril by AstraZeneca, and Laxicon by Stadmed.
Dioctyl sodium sulfosuccinate is used as asurfactant in a wide range of applications, often under the name Aerosol-OT.[4][26] It is unusual in that it can formmicroemulsions without the use of co-surfactants, and it has a rich variety of aqueous-phase behavior including multiple liquid crystalline phases.[27]
Dioctyl sodium sulfosuccinate has been approved by theUS FDA as a "generally recognized as safe" (GRAS) additive.[28] It is used in a variety of food products, as a surface active agent,stabilizer,thickener,wetting agent, processing aid,solubilizing agent,emulsifier, anddispersant. The highest amount found in food products is 0.5% by weight, which include pasteurized cheese spreads, cream cheeses and salad dressings.[29] The FDA also approved its use as a wetting agent or solubilizer for flavoring agents incarbonated and non-carbonated drinks at levels up to 10 parts per million.[28]
Sodium docusate is the most widely used surfactant in reversemicelleencapsulation studies.[30]
As a surfactant, docusate sodium is or has been commercialized under many brand names, including DSS, Aerosol OT, Alphasol OT, Colace, Complemix, Coprol, Dioctylal, Dioctyl-Medo Forte, Diotilan, Diovac, Disonate, Doxinate, Doxol, Dulsivac, Molatoc, Molofac, Nevax, Norval, Regutol, Softili, Solusol, Sulfimel DOS, Vatsol OT, Velmol, and Waxsol[31]
Thestructural formula of the docusate anion isR−O−C(=O)−CH(SO−3)−CH2−C(=O)−O−R, where R is the2-ethylhexyl groupH3C−(CH2)3−C(−CH2−CH3)H−CH2−. Theconjugate acid can be described as the twofoldcarboxylate ester ofsulfosuccinic acid with2-ethylhexanol.
The compound is a white, wax-like, plastic solid, with an odor suggestive ofoctyl alcohol. It starts to decompose at about 220 °C.[31]
The solubility of dioctyl sodium sulfosuccinate in water is 14 g/L at 25 °C, increasing to 55 g/L at 70 °C.[31] Solubility is better in lesspolar solvents: 1:30 inethanol, 1:1 inchloroform anddiethylether, and practically unlimited inpetroleum ether (25 °C). It also is highly soluble inglycerol, although this is a rather polar solvent. It is also highly soluble inxylene,oleic acid,acetone,diacetone alcohol,methanol,isopropanol,2-butanol,methyl acetate,ethyl acetate,furfurol, andvegetable oils.[31]
Theester groups are easily cleaved underbasic conditions, but are stable againstacids.[18]
Sodium dioctyl sulfosuccinate can be obtained by treatingdioctyl maleate withsodium bisulfite. Thebisulfite anion adds to thedouble bond:
Ingestion may cause the side effects described above, such as diarrhea, intestinal bloating, and occasionally cramping pains. Dioctyl sodium sulfosuccinate is not known to becarcinogenic,mutagenic, orteratogenic.[32]
Dioctyl sodium sulfosuccinate is of low toxicity forcrustaceans such as thehermit crabClibanarius erythropus and the shrimpCrangon crangon. Toxicity formolluscs varies widely, with 48-hourLD50 found between 5 mg/L for thecommon limpet and 100 mg/L for thecommon periwinkle. Various species ofphytoplankton have an LD50 around 8 mg/L.
In a 2010 study, dioctyl sodium sulfosuccinate exhibited higher toxicity against bacteria (Vibrio fischeri,Anabaena sp.) and algae (Pseudokirchneriella subcapitata) than did a number of fluorinated surfactants (PFOS,PFOA, orPFBS). Measuringbioluminescence inhibition of the bacteria and growth inhibition of the algae, the LD50 were in the range of 43–75 mg/L. Combinations of the fluorinated compounds with dioctyl sodium sulfosuccinate showed mid to highly synergistic effects in most settings, meaning that such combinations are significantly more toxic than the individual substances.[33]
The substance is highly toxic forrainbow trout with a median lethal concentration (LC50) of 0.56 mg/L after 48 hours for the pure substance. It is only slightly to moderately toxic for rainbow trout fingerlings, and slightly toxic forharlequin rasboras (LC50 27 mg/L of a 60% formulation after 48 hours).
