A self-microemulsifying drug delivery system (SMEDDS) is a

drug delivery Drug delivery involves various methods and technologies designed to transport pharmaceutical compounds to their target sites helping therapeutic effect. It involves principles related to drug preparation, route of administration, site-specif ...

system that uses a

microemulsion Microemulsions are clear, thermodynamically stable, isotropic liquid mixtures of oil, water and surfactant, frequently in combination with a cosurfactant. The aqueous phase may contain salt(s) and/or other ingredients, and the "oil" may actuall ...

achieved by chemical rather than mechanical means. That is, by an intrinsic property of the drug formulation, rather than by special mixing and handling. It employs the familiar

ouzo effect The ouzo effect ( ), also known as the wikt:louche#French, louche effect ( ) and spontaneous emulsification, is the phenomenon of formation of a milky oil-in-water emulsion when water is added to ouzo and other :Anise liqueurs and spirits, anise- ...

displayed by

anethole Anethole (also known as anise camphor) is an organic compound that is widely used as a flavoring substance. It is a derivative of the aromatic compound allylbenzene and occurs widely in the essential oils of plants. It is in the class of phenylpr ...

in many

anise Anise (; '), also called aniseed or rarely anix, is a flowering plant in the family Apiaceae native to the eastern Mediterranean region and Southwest Asia. The flavor and aroma of its seeds have similarities with some other spices and herbs, ...

-flavored

liquor Liquor ( , sometimes hard liquor), spirits, distilled spirits, or spiritous liquor are alcoholic drinks produced by the distillation of grains, fruits, vegetables, or sugar that have already gone through ethanol fermentation, alcoholic ferm ...

s. Microemulsions have significant potential for use in drug delivery, and SMEDDS (including so-called "U-type" microemulsions) are the best of these systems identified to date. SMEDDS are of particular value in increasing the absorption of

lipophilic Lipophilicity (from Greek language, Greek λίπος "fat" and :wikt:φίλος, φίλος "friendly") is the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such compounds are c ...

drugs taken by mouth. SMEDDS in research or development include formulations of the drugs anethole trithione, oridonin,

curcumin Curcumin is a bright yellow chemical produced by plants of the ''Curcuma longa'' species. It is the principal curcuminoid of turmeric (''Curcuma longa''), a member of the ginger family, Zingiberaceae. It is sold as a herbal supplement, cosmetic ...

vinpocetine Vinpocetine (ethyl apovincaminate), sold under the brand name Cavinton among others, is a synthetic derivative (chemistry), derivative of the vinca alkaloid vincamine, differing by the removal of a hydroxyl group and by being the ethyl rather th ...

tacrolimus Tacrolimus, sold under the brand name Prograf among others, is an immunosuppressive drug. After Allotransplantation, allogenic organ transplant, the risk of organ Transplant rejection, rejection is moderate. To lower the risk of organ rejectio ...

mitotane Mitotane, sold under the brand name Lysodren, is a steroidogenesis inhibitor and cytostatic antineoplastic medication which is used in the treatment of adrenocortical carcinoma and Cushing's syndrome. It is a chemical derivative, derivative of ...

berberine hydrochloride Berberine is a quaternary ammonium salt from the protoberberine group of benzylisoquinoline alkaloids, occurring naturally as a secondary metabolite in some plants including species of ''Berberis'', from which its name is derived. Due to their y ...

, nobiletin,

piroxicam Piroxicam is a nonsteroidal anti-inflammatory drug (NSAID) of the oxicam class used to relieve the symptoms of painful inflammatory conditions like arthritis. Piroxicam works by preventing the production of endogenous prostaglandins which are inv ...

, anti-

malaria Malaria is a Mosquito-borne disease, mosquito-borne infectious disease that affects vertebrates and ''Anopheles'' mosquitoes. Human malaria causes Signs and symptoms, symptoms that typically include fever, Fatigue (medical), fatigue, vomitin ...

drugs beta-artemether and

halofantrine Halofantrine is a drug used to treat malaria. Halofantrine's structure contains a substituted phenanthrene, and is related to the antimalarial drugs quinine and lumefantrine. Marketed as Halfan, halofantrine is never used to prevent malaria and ...

, anti-

HIV The human immunodeficiency viruses (HIV) are two species of '' Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the im ...

drug UC 781,

nimodipine Nimodipine, sold under the brand name Nimotop among others, is a calcium channel blocker used in preventing vasospasm secondary to subarachnoid hemorrhage (a form of cerebral hemorrhage). It was originally developed within the calcium channel b ...

exemestane Exemestane, sold under the brand name Aromasin among others, is a medication used to treat breast cancer. It is a member of the class of antiestrogens known as aromatase inhibitors. Some breast cancers require estrogen to grow. Those cancers ha ...

, anti-

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

drugs 9-nitrocamptothecin (9-NC)

paclitaxel Paclitaxel, sold under the brand name Taxol among others, is a chemotherapy medication used to treat ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposi's sarcoma, cervical cancer, and pancreatic cancer. It is administered b ...

, and seocalcitol,

alprostadil Prostaglandin E1 (PGE1) is a naturally occurring prostaglandin with various medical uses. Alprostadil and misoprostol are synthetic forms of prostaglandin E1 used as medications. Lubiprostone, a derivative of prostaglandin E1, is also used as ...

( intraurethral use),

probucol Probucol, sold under the trade name Lorelco among others, is an lipid-lowering agent initially developed for the treatment of coronary artery disease. Clinical use was discontinued in some countries after it was found that the drug may have the ...

itraconazole Itraconazole, sometimes abbreviated ITZ, is an antifungal medication used to treat a number of fungal infections. This includes aspergillosis, blastomycosis, coccidioidomycosis, histoplasmosis, and paracoccidioidomycosis. It may be given ...

fenofibrate Fenofibrate, sold under the brand name Tricor among others, is an oral medication of the fibrate class used to treat abnormal blood lipid levels. It is less commonly used compared to statins because it treats a different type of cholesterol a ...

acyclovir Aciclovir, also known as acyclovir, is an antiviral medication. It is primarily used for the treatment of herpes simplex virus infections, chickenpox, and shingles. Other uses include the prevention of cytomegalovirus infections following tran ...

simvastatin Simvastatin, sold under the brand name Zocor among others, is a statin, a type of lipid-lowering medication. It is used along with exercise, diet, and weight loss to decrease hyperlipidemia, elevated lipid levels. It is also used to decrease t ...

, xibornol,

silymarin Silibinin (INN), also known as silybin (both from ''Silybum'', the generic name of the plant from which it is extracted), is the major active constituent of silymarin, a standardized extract of the milk thistle, containing a mixture of flavon ...

, alpha-asarone, enilconazole, puerarin (an

isoflavone Isoflavones are a type of naturally-occurring isoflavonoids, many of which act as phytoestrogens in mammals. Isoflavones occur in many plant species, but are especially high in soybeans. Although isoflavones and closely-related phytoestrogens ar ...

found in ''

Pueraria lobata ''Pueraria montana'' var. ''lobata'', the East Asian arrowroot, or kudzu vine, is a perennial plant in the family Fabaceae. Names It is called ''gé'' () in Chinese, in Japanese, and ''chik'' () or ''gal'' () in Korean. Description The ...

''),

atorvastatin Atorvastatin, sold under the brand name Lipitor among others, is a statin medication used to prevent cardiovascular disease in those at high risk and to treat abnormal lipid levels. For the prevention of cardiovascular disease, statins are a ...

heparin Heparin, also known as unfractionated heparin (UFH), is a medication and naturally occurring glycosaminoglycan. Heparin is a blood anticoagulant that increases the activity of antithrombin. It is used in the treatment of myocardial infarction, ...

carvedilol Carvedilol, sold under the brand name Coreg among others, is a beta blocker medication, that may be prescribed for the treatment of high blood pressure (hypertension) and chronic heart failure with reduced ejection fraction (also known as HFrEF ...

ketoconazole Ketoconazole, sold under the brand name Nizoral, among others, is an antiandrogen, antifungal drug, antifungal, and antiglucocorticoid medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin inf ...

gentamicin Gentamicin is an aminoglycoside antibiotic used to treat several types of bacterial infections. This may include bone infections, endocarditis, pelvic inflammatory disease, meningitis, pneumonia, urinary tract infections, and sepsis amo ...

, labrasol,

flurbiprofen Flurbiprofen is a member of the phenylalkanoic acid derivative family of nonsteroidal anti-inflammatory drugs (NSAIDs). It is primarily indicated as a pre-operative anti-miotic (in an ophthalmic solution) as well as orally for arthritis or den ...

celecoxib Celecoxib, sold under the brand name Celebrex among others, is a COX-2 inhibitor and nonsteroidal anti-inflammatory drug (NSAID). It is used to treat the pain and inflammation in osteoarthritis, acute pain in adults, rheumatoid arthritis, psor ...

danazol Danazol, sold as Danocrine and other brand names, is a medication used in the treatment of endometriosis, fibrocystic breast disease, hereditary angioedema and other conditions. It is taken oral administration, by mouth. The use of danazol is ...

cyclosporine Ciclosporin, also spelled cyclosporine and cyclosporin, is a calcineurin inhibitor, used as an immunosuppressant medication. It is taken orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's disease, nephrotic syndrome, ecz ...

, and

idebenone Idebenone, sold under the brand name Raxone among others, is a medication that was initially developed by Takeda Pharmaceutical Company for the treatment of Alzheimer's disease and other cognitive defects. This has been met with limited success ...

. Actual applications of ''Self-microemulsifying drug delivery system (SMEDDS) remain rare. The first drug marketed as a SMEDDS was

cyclosporin Ciclosporin, also spelled cyclosporine and cyclosporin, is a calcineurin inhibitor, used as an immunosuppressant medication. It is taken orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's disease, nephrotic syndrome, ecz ...

, and it had significantly improved bioavailability compared with the conventional solution. In the last decade, several SMEDDS loaded with antiviral drugs (

ritonavir Ritonavir, sold under the brand name Norvir, is an antiretroviral medication used along with other medications to treat HIV/AIDS. This combination treatment is known as highly active antiretroviral therapy (HAART). Ritonavir is a protease inhi ...

saquinavir Saquinavir, sold under the brand name Invirase among others, is an antiretroviral medication used together with other medications to treat or prevent HIV/AIDS. Typically it is used with ritonavir or lopinavir/ritonavir to increase its effect. I ...

) were tested for treatment of HIV infection, but the relative improvement in clinical benefit was not significant. The SMEDDS formulation of

(soft capsules) has been withdrawn in some countries. Within the last years SMEDDS were also utilized for the oral administration of biologics. Due to ion pairing with appropriate surfactants these mainly hydrophilic macromolecular drugs can be incorporated in the lipophilic phase of SMEDDS. Provided that the oily droplets being formed in the gut are sufficiently stable towards lipases, can permeate the mucus gel layer in sufficient quantities and exhibit permeation enhancing properties the oral bioavailability of various biologics can be strongly improved SMEDDS offer numerous advantages: spontaneous formation, ease of manufacture, thermodynamic stability, and improved solubilization of bioactive materials. Improved solubility contributes to faster release rates and greater bioavailability. For many drugs taken by mouth, faster release rates improve the drug acceptance by consumers. Greater bioavailability means that less drug need be used; this may lower cost, and does lower the stomach irritation and toxicity of drugs taken by mouth. For oral use, SMEDDS may be formulated as liquids or solids, the solids packaged in capsules or tablets. Limited studies comparing these report that in terms of bioavailability liquid SMEDDS are superior to solid SMEDDS, which are superior to conventional tablets. Liquid SMEDDS have also shown value in injectable (IV and urethral) formulations and in a topical (oral) spray.

See also

References

Further reading