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

drug delivery Drug delivery refers to approaches, formulations, manufacturing techniques, storage systems, and technologies involved in transporting a pharmaceutical compound to its target site to achieve a desired therapeutic effect. Principles related to dr ...

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 actually be ...

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 louche effect and spontaneous emulsification) is a milky (''louche'') oil-in-water emulsion that is formed when water is added to ouzo and other anise-flavored liqueurs and spirits, such as pastis, rakı, arak, sambuca a ...

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 phenylpropene, a type of aromatic compound that occurs widely in nature, in essential oils. It is in the class of ph ...

in many

anise Anise (; '), also called aniseed or rarely anix is a flowering plant in the family Apiaceae native to Eurasia. The flavor and aroma of its seeds have similarities with some other spices and herbs, such as star anise, fennel, licorice, and t ...

-flavored

liquor Liquor (or a spirit) is an alcoholic drink produced by distillation of grains, fruits, vegetables, or sugar, that have already gone through alcoholic fermentation. Other terms for liquor include: spirit drink, distilled beverage or ha ...

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 λίπος "fat" and φίλος "friendly"), refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such non-polar solvents are themselves li ...

drugs taken by mouth. SMEDDS in research or development include formulations of the drugs

anethole trithione Anethole trithione, anetholtrithione, or anetholtrithion ( JAN) is a drug used in the treatment of dry mouth. It is listed in the U.S. National Cancer Institute's ''Dictionary of Cancer Terms'' as being studied in the treatment of cancer.

, 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, cos ...

vinpocetine Vinpocetine (ethyl apovincaminate) is a synthetic derivative of the vinca alkaloid vincamine, differing by the removal of a hydroxyl group. Vincamine is extracted from either the seeds of '' Voacanga africana'' or the leaves of ''Vinca minor'' (l ...

tacrolimus Tacrolimus, sold under the brand name Prograf among others, is an immunosuppressive drug. After allogeneic organ transplant, the risk of organ rejection is moderate. To lower the risk of organ rejection, tacrolimus is given. The drug can als ...

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 derivative of the early insecticide ...

berberine hydrochloride Berberine is a Quaternary ammonium cation, quaternary ammonium salt from the protoberberine group of benzylisoquinoline alkaloids found in such plants as ''Berberis vulgaris'' (barberry), ''Berberis aristata'' (tree turmeric), ''Mahonia aquifoliu ...

nobiletin Nobiletin is a flavonoid isolated from citrus peels. It is an ''O''-methylated flavone that has the activity to rescue bulbectomy-induced memory impairment. Potential pharmacology Nobiletin was found to potentially inhibit cartilage degradation ...

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 i ...

, anti-

malaria Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or deat ...

drugs

beta-artemether Artemether is a medication used for the treatment of malaria. The injectable form is specifically used for severe malaria rather than quinine. In adults, it may not be as effective as artesunate. It is given by injection in a muscle. It is also a ...

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 i ...

, 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 immu ...

drug

UC 781 UC may refer to: Arts and entertainment * ''University Challenge'', a popular British quiz programme airing on BBC Two ** ''University Challenge (New Zealand)'', the New Zealand version of the British programme * Universal Century, one of the tim ...

nimodipine Nimodipine, sold under the brand name Nimotop among others, is 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 hav ...

, anti-

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bl ...

drugs

9-nitrocamptothecin Rubitecan (INN, marketing name Orathecin) is an oral topoisomerase inhibitor, developed by SuperGen (now Astex Pharmaceuticals, Inc'.; a member of the Otsuka Group'). History On January 27, 2004, SuperGen announced that it has completed the submi ...

(9-NC)

paclitaxel Paclitaxel (PTX), sold under the brand name Taxol among others, is a chemotherapy medication used to treat a number of types of cancer. This includes ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposi's sarcoma, cervical can ...

, and seocalcitol,

alprostadil Prostaglandin E1 (PGE1), also known as alprostadil, is a naturally occurring prostaglandin which is used as a medication. In infants with congenital heart defects, it is delivered by slow injection into a vein to open the ductus arteriosus un ...

( intraurethral use),

probucol Probucol, sold under the trade name Lorelco among others, is an anti- hyperlipidemic drug initially developed for the treatment of coronary artery disease. Clinical development was discontinued after it was found that the drug may have the undesi ...

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 by mout ...

fenofibrate Fenofibrate (sold under the brand names ''Tricor'', ''Fenobrat'' etc.), is an oral medication of the fibrate class used to treat abnormal blood lipid levels. It is less commonly used compared than statins because it treats a different type of ...

acyclovir Aciclovir (ACV), 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 prevention of cytomegalovirus infections following tra ...

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 elevated lipid levels. It is also used to decrease the risk of hea ...

xibornol Xibornol is a lipophilic substance with antiseptic properties, mainly used in Italy and Spain. It is primarily administered to the throat as a spray mouthwash. As of 2007, all approved forms are water-based suspensions. The drug was discovered ...

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 seeds, containing a mixture of fl ...

, alpha-asarone,

enilconazole Enilconazole (synonyms imazalil, chloramizole) is a fungicide widely used in agriculture, particularly in the growing of citrus fruits. Trade names include Freshgard, Fungaflor, and Nuzone. Enilconazole is also used in veterinary medicine as a t ...

puerarin Puerarin, one of several known isoflavones, is found in a number of plants and herbs, such as the root of ''Pueraria'' (''Radix puerariae'') notably of the kudzu plant. Puerarin is the 8-''C''-glucoside of daidzein. List of plants that contain ...

(an

isoflavone Isoflavones are substituted derivatives of isoflavone, a type of naturally occurring isoflavonoids, many of which act as phytoestrogens in mammals. Isoflavones are produced almost exclusively by the members of the bean family, Fabaceae (Leguminos ...

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, ''kuzu'' () in Japanese, and ''chik'' () or ''gal'' (갈; 葛) in Korean. ...

''),

atorvastatin Atorvastatin 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 first-line treatment. It is taken by mouth. Common ...

heparin Heparin, also known as unfractionated heparin (UFH), is a medication and naturally occurring glycosaminoglycan. Since heparins depend on the activity of antithrombin, they are considered anticoagulants. Specifically it is also used in the trea ...

carvedilol Carvedilol, sold under the brand name Coreg among others, is a medication used to treat high blood pressure, congestive heart failure (CHF), and left ventricular dysfunction in people who are otherwise stable. For high blood pressure, it is g ...

ketoconazole Ketoconazole, sold under the brand name Nizoral among others, is an antiandrogen and antifungal medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin infections such as tinea, cutaneous can ...

gentamicin Gentamicin is an 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 among others. It is not ...

, 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 denta ...

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, ...

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 by mouth. The use of danazol is limited by masculi ...

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

, and

idebenone Idebenone (pronounced eye-deb-eh-known, trade names Catena, Raxone, Sovrima, among others) is a drug that was initially developed by Takeda Pharmaceutical Company for the treatment of Alzheimer's disease and other cognitive defects. This has been ...

. 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 a natural product. It is taken orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's disease, ...

, 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 drug used along with other medications to treat HIV/AIDS. This combination treatment is known as highly active antiretroviral therapy (HAART). Ritonavir is a protease inhibitor a ...

saquinavir Saquinavir (SQV), sold under the brand names Invirase and Fortovase, is an antiretroviral drug used together with other medications to treat or prevent HIV/AIDS. Typically it is used with ritonavir or lopinavir/ritonavir to increase its effect. ...

) 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