Docusate

Sodium docusate was patented in 1937 by Coleman R. Caryl and Alphons O. Jaeger for American Cyanamid,{{cite patent | country = US | number = 2181087 | inventor = Caryl CR, Jaeger AO | assign1 = American Cyanamid | gdate = 21 November 1939 | fdate = 7 July 1937 | title = Detergent composition }} which commercialized it for many years as a detergent under the brand name Aerosol OT.

Its use for the treatment of constipation was first proposed in 1955 by James L. Wilson and David G. Dickinson,{{cite journal | vauthors = Wilson JL, Dickinson DG | title = Use of dioctyl sodium sulfosuccinate (aerosol O.T.) for severe constipation | journal = Journal of the American Medical Association | volume = 158 | issue = 4 | pages = 261–3 | date = May 1955 | pmid = 14367076 | doi = 10.1001/jama.1955.02960040019006a }} and quickly popularized under the name Doxinate.{{cite journal | vauthors = Friedman M | title = Dioctyl sodium sulfosuccinate (doxinate) in chronic functional constipation | journal = American Practitioner and Digest of Treatment | volume = 7 | issue = 10 | pages = 1588–91 | date = October 1956 | pmid = 13362832 }}

The main medical use of docusate sodium is to treat constipation, acting as a laxative and stool softener. In painful anorectal conditions such as hemorrhoid and anal fissures, it can help avoid pain caused by straining during bowel movements.

When administered by mouth, a bowel movement often occurs in 1 to 3 days, while rectal use may be effective within 20 minutes.{{cite web |title=Docusate sodium |url=http://www.nursingtimes.net/nursing-practice-clinical-research/docusate-sodium/203939.article | archive-url = https://web.archive.org/web/20110721023904/https://www.nursingtimes.net/clinical-archive/medicine-management/docusate-sodium-18-12-2004/ | archive-date = 21 July 2011 |access-date=6 March 2019 |date=18 December 2004}}

Sodium docusate is recommended as a stool softener for children.

However, its effectiveness for constipation is poorly supported by evidence.{{cite journal | vauthors = Fakheri RJ, Volpicelli FM | title = Things We Do for No Reason: Prescribing Docusate for Constipation in Hospitalized Adults | journal = Journal of Hospital Medicine | volume = 14 | issue = 2 | pages = 110–113 | date = February 2019 | pmid = 30785419 | doi = 10.12788/jhm.3124 | doi-access = free }}{{cite journal | title = Dioctyl Sulfosuccinate or Docusate (Calcium or Sodium) for the Prevention or Management of Constipation: A Review of the Clinical Effectiveness | journal = CADTH Rapid Response Reports. | date = 26 June 2014 | pmid = 25520993 | url = https://www.ncbi.nlm.nih.gov/books/NBK259243/ }} Multiple studies have found docusate to be no more effective than a placebo for improving constipation.{{cite journal | vauthors = Candy B, Jones L, Larkin PJ, Vickerstaff V, Tookman A, Stone P | title = Laxatives for the management of constipation in people receiving palliative care | journal = The Cochrane Database of Systematic Reviews | volume = 13 | issue = 5 | pages = CD003448 | date = May 2015 | pmid = 25967924 | pmc = 6956627 | doi = 10.1002/14651858.CD003448.pub4 | url = http://discovery.ucl.ac.uk/1473363/1/Candy_et_al-2015-The_Cochrane_Library%20laxatives.pdf }}{{cite journal | vauthors = Ramkumar D, Rao SS | title = Efficacy and safety of traditional medical therapies for chronic constipation: systematic review | journal = The American Journal of Gastroenterology | volume = 100 | issue = 4 | pages = 936–71 | date = April 2005 | doi = 10.1111/j.1572-0241.2005.40925.x | pmid = 15784043 | s2cid = 13869933 }} Others have found it to be less useful for the treatment of chronic constipation than psyllium.{{cite journal | vauthors = Portalatin M, Winstead N | title = Medical management of constipation | journal = Clinics in Colon and Rectal Surgery | volume = 25 | issue = 1 | pages = 12–9 | date = March 2012 | pmid = 23449608 | pmc = 3348737 | doi = 10.1055/s-0032-1301754 }}{{cite book|title=Arzneistoff-Profile| veditors = Dinnendahl V, Fricke U |publisher=Govi Pharmazeutischer Verlag|location=Eschborn, Germany|year=2010|edition=23|volume=2|isbn=978-3-7741-9846-3|language=de}}

The medication may be given to people who are receiving opioid medication, although prolonged use may cause irritation of the gastrointestinal tract.

Docusate sodium, when used with ear syringing, may help with earwax removal, particularly in the case of impaction.{{cite web | title = How effective is docusate as a cerumenolytic agent? | work = GlobalRPH.com | url = http://www.globalrph.com/docusate.htm | archive-url = https://web.archive.org/web/20101123215229/http://globalrph.com/docusate.htm | archive-date=23 November 2010 }}

Sodium docusate is also used as a lubricant in the production of tablets and as an emulsifier in topical preparations and other suspensions.{{cite book|title=Austria-Codex Stoffliste| veditors = Jasek W | publisher=Österreichischer Apothekerverlag|location=Vienna|year=2008|edition=41st |page=316|isbn=978-3-85200-190-6|language=de}}

Docusate sodium is approved and recommended as safe during pregnancy and breastfeeding.{{cite book| vauthors = Yaffe SJ |title=Drugs in pregnancy and lactation: a reference guide to fetal and neonatal risk|date=2011|publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins|location=Philadelphia|isbn=9781608317080|page=1651|edition=9th |url=https://books.google.com/books?id=OIgTE4aynrMC&pg=PA1651}}{{cite journal | vauthors = Mahadevan U, Kane S | title = American gastroenterological association institute medical position statement on the use of gastrointestinal medications in pregnancy | journal = Gastroenterology | volume = 131 | issue = 1 | pages = 278–82 | date = July 2006 | pmid = 16831610 | doi = 10.1053/j.gastro.2006.04.048 | doi-access = free }}

Docusate is not recommended in people with appendicitis, acute abdomen, or ileus.

When taken by mouth it should be ingested with plenty of water.

Side effects are uncommon and typically mild, and may include stomach pain, abdominal cramps or diarrhea, Efficacy decreases with long-term use, and may cause poor bowel function.{{cite book|title=2013 Nurse's Drug Handbook.|date=2013|publisher=Jones & Bartlett Learning|location=Burlington, MA|isbn=9781449642846|page=[https://archive.org/details/2013nursesdrugha0012unse/page/366 366]|url=https://archive.org/details/2013nursesdrugha0012unse|url-access=registration}}

Serious allergic reactions may occur with the drug. The most severe side effect of docusate, although very rare, is rectal bleeding.drugs.com: [https://www.drugs.com/cdi/docusate.html Docusate] {{webarchive|url=https://web.archive.org/web/20100716133214/http://www.drugs.com/cdi/docusate.html |date=16 July 2010}}

Docusate might increase the resorption of other drugs, for example, dantron (1,8-dihydroxyanthraquinone).

Docusate is an anionic surfactant, which works by reducing the surface tension of the stool, allowing more intestinal water and fat to combine with the stool.{{Cite book | vauthors = Shaw D | chapter = Drugs Acting on the Gastrointestinal Tract| title = Pharmacology and Therapeutics for Dentistry | edition = Seventh |year=2017|pages=404–416|doi=10.1016/B978-0-323-39307-2.00028-X|isbn=9780323393072|via=Elsevier Science Direct}}{{cite book| vauthors = Hamilton RJ |title=Tarascon pocket pharmacopoeia : 2013 classic shirt-pocket edition|date=2013|publisher=Jones & Bartlett Learning|location=Burlington, Ma.|isbn=9781449665869|page=112|edition=27|url=https://books.google.com/books?id=lwueJ4IAl4oC&pg=PA112}} This decreases the strain and discomfort associated with constipation.

It does not stay in the gastrointestinal tract but is absorbed into the bloodstream and excreted via the gallbladder 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 with senna.

In India, preparations include Laxatin by Alembic, Doslax by Raptakos Laboratories, Cellubril by AstraZeneca, and Laxicon by Stadmed.

Dioctyl sodium sulfosuccinate is used as a surfactant in a wide range of applications, often under the name Aerosol-OT.{{cite journal | vauthors = Whiffen AJ | title = Aerosol OT in the preparation of microscopic mounts of fungi | journal = Mycologia | volume = 38 | pages = 346 | date = 1946 | pmid = 20983186 | doi = 10.1080/00275514.1946.12024063 }} It is unusual in that it can form microemulsions without the use of co-surfactants, and it has a rich variety of aqueous-phase behavior including multiple liquid crystalline phases.{{cite journal| vauthors = Nave S, Eastoe J, Penfold J |title=What Is So Special about Aerosol-OT? 1. Aqueous Systems|journal=Langmuir|date=November 2000|volume=16|issue=23|pages=8733–8740|doi=10.1021/la000341q}}

Dioctyl sodium sulfosuccinate has been approved by the US FDA as a "generally recognized as safe" (GRAS) additive. It is used in a variety of food products, as a surface active agent, stabilizer, thickener, wetting agent, processing aid, solubilizing agent, emulsifier, and dispersant. The highest amount found in food products is 0.5% by weight, which include pasteurized cheese spreads, cream cheeses and salad dressings.{{cite web |title=CFR - Code of Federal Regulations Title 21 |url=https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm |website=www.accessdata.fda.gov |access-date=29 January 2020}} The FDA also approved its use as a wetting agent or solubilizer for flavoring agents in carbonated and non-carbonated drinks at levels up to 10 parts per million.{{cite web | work = Center for Food Safety and Applied Nutrition. | date = 20 July 1998 | title = GRAS Notice Inventory Agency Response Letter GRAS Notice No. GRN 000006 | access-date = 24 January 2020 | url = https://www.fda.gov/Food/IngredientsPackagingLabeling/GRAS/NoticeInventory/ucm154917.htm | archive-url = https://wayback.archive-it.org/7993/20171031034954/https://www.fda.gov/Food/IngredientsPackagingLabeling/GRAS/NoticeInventory/ucm154917.htm | archive-date = 31 October 2017 }}

Sodium docusate is the most widely used surfactant in reverse micelle encapsulation studies.{{cite journal | vauthors = Flynn PF | title = Multidimensional multinuclear solution NMR studies of encapsulated macromolecules | journal = Prog. Nucl. Magn. Reson. Spectrosc. | year = 2004 | volume = 45 | issue = 1–2 | pages = 31–51 | doi = 10.1016/j.pnmrs.2004.04.003| bibcode = 2004PNMRS..45...31F }}

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{{cite book | vauthors = Ahuja S, Cohen J | chapter = Dioctyl Sodium Sulfosuccinate | title = InAnalytical Profiles of Drug Substances | date = January 1973 | volume = 2 | pages = 199–219 | publisher = Academic Press | doi = 10.1016/S0099-5428(08)60040-4 | isbn = 9780122608025 }}

The structural formula of the docusate anion is {{chem2|R\sO\sC(\dO)\sCH(SO3(−))\sCH2\sC(\dO)\sO\sR}}, where R is the 2-ethylhexyl group {{chem2|H3C\s(CH2)3\sC(\sCH2\sCH3)H\sCH2\s}}. The conjugate acid can be described as the twofold carboxylate ester of sulfosuccinic acid with 2-ethylhexanol.

The compound is a white, wax-like, plastic solid, with an odor suggestive of octyl alcohol. It starts to decompose at about 220 °C.

The solubility of dioctyl sodium sulfosuccinate in water is 14 g/L at 25 °C, increasing to 55 g/L at 70 °C. Solubility is better in less polar solvents: 1:30 in ethanol, 1:1 in chloroform and diethylether, and practically unlimited in petroleum ether (25 °C). It also is highly soluble in glycerol, although this is a rather polar solvent. It is also highly soluble in xylene, oleic acid, acetone, diacetone alcohol, methanol, isopropanol, 2-butanol, methyl acetate, ethyl acetate, furfurol, and vegetable oils.

The ester groups are easily cleaved under basic conditions, but are stable against acids.

Sodium dioctyl sulfosuccinate can be obtained by treating dioctyl maleate with sodium bisulfite. The bisulfite anion adds to the double bond:

: {{chem2|\sCH\dCH\s}} + {{chem2|HSO3(−)}} {{chem2|→}} {{chem2|\sCH(\sSO3(−))\sCH2\s}}

Ingestion may cause the side effects described above, such as diarrhea, intestinal bloating, and occasionally cramping pains. Dioctyl sodium sulfosuccinate is not known to be carcinogenic, mutagenic, or teratogenic.ScienceLab.com: [http://www.sciencelab.com/xMSDS-Docusate_sodium-9923877 Docusate sodium Material Safety Data Sheet] {{webarchive|url=https://web.archive.org/web/20061017145721/http://www.sciencelab.com/xMSDS-Docusate_sodium-9923877 |date=17 October 2006 }}

Dioctyl sodium sulfosuccinate is of low toxicity for crustaceans such as the hermit crab Clibanarius erythropus and the shrimp Crangon crangon. Toxicity for molluscs varies widely, with 48-hour LD₅₀ found between 5 mg/L for the common limpet and 100 mg/L for the common periwinkle. Various species of phytoplankton 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, or PFBS). Measuring bioluminescence 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.{{cite journal | vauthors = Rosal R, Rodea-Palomares I, Boltes K, Fernández-Piñas F, Leganés F, Petre A | title = Ecotoxicological assessment of surfactants in the aquatic environment: combined toxicity of docusate sodium with chlorinated pollutants | journal = Chemosphere | volume = 81 | issue = 2 | pages = 288–93 | date = September 2010 | pmid = 20579683 | doi = 10.1016/j.chemosphere.2010.05.050 | bibcode = 2010Chmsp..81..288R }}

The substance is highly toxic for rainbow 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 for harlequin rasboras (LC₅₀ 27 mg/L of a 60% formulation after 48 hours).

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