A self-microemulsifying drug delivery system (SMEDDS) is a drug delivery system that uses a microemulsion 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 displayed by anethole in many anise-flavored liquors. 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. [1] SMEDDS are of particular value in increasing the absorption of lipophilic drugs taken by mouth.
SMEDDS in research or development include formulations of the drugs anethole trithione, [2] oridonin, [3] [4] [5] curcumin, [6] vinpocetine, [7] [8] tacrolimus, [9] [10] [11] mitotane, berberine hydrochloride, [12] nobiletin, [13] piroxicam, [14] [15] anti-malaria drugs beta-artemether [16] and halofantrine, [17] [18] anti-HIV drug UC 781, [19] [20] nimodipine, [21] [22] exemestane, [23] anti-cancer drugs 9-nitrocamptothecin (9-NC) [24] paclitaxel, [25] [26] and seocalcitol, [27] [28] alprostadil (intraurethral use), [29] probucol, [18] [30] itraconazole, [31] fenofibrate, [32] acyclovir, [33] simvastatin, [34] [35] xibornol, [36] silymarin, [37] [38] alpha-asarone, [39] enilconazole, [19] puerarin (an isoflavone found in Pueraria lobata ), [40] [41] [42] [43] atorvastatin, [44] [45] [46] heparin, [47] carvedilol, [48] ketoconazole, [49] gentamicin, [50] labrasol, [51] flurbiprofen, [52] celecoxib, [53] danazol, [54] cyclosporine, [55] and idebenone. [56]
Actual applications of Self-microemulsifying drug delivery system' (SMEDDS) remain rare. The first drug marketed as a SMEDDS was cyclosporin, and it had significantly improved bioavailability compared with the conventional solution. In the last decade, several SMEDDS loaded with antiviral drugs (ritonavir, saquinavir) were tested for treatment of HIV infection, but the relative improvement in clinical benefit was not significant. The SMEDDS formulation of ritonavir (soft capsules) has been withdrawn in some countries. [57]
Within the last years SMEDDS were also utilized for the oral administration of biologics. Due to ion pairing with appropriate surfactants [58] 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, [59] can permeate the mucus gel layer in sufficient quantities [60] and exhibit permeation enhancing properties [61] the oral bioavailability of various biologics can be strongly improved [62]
SMEDDS offer numerous advantages: spontaneous formation, ease of manufacture, thermodynamic stability, and improved solubilization of bioactive materials. [1] 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, [21] which are superior to conventional tablets. [21] [42] [47] Liquid SMEDDS have also shown value in injectable (IV and urethral) formulations and in a topical (oral) spray. [36]
An emulsion is a mixture of two or more liquids that are normally immiscible owing to liquid-liquid phase separation. Emulsions are part of a more general class of two-phase systems of matter called colloids. Although the terms colloid and emulsion are sometimes used interchangeably, emulsion should be used when both phases, dispersed and continuous, are liquids. In an emulsion, one liquid is dispersed in the other. Examples of emulsions include vinaigrettes, homogenized milk, liquid biomolecular condensates, and some cutting fluids for metal working.
In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation.
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 drug preparation, route of administration, site-specific targeting, metabolism, and toxicity are used to optimize efficacy and safety, and to improve patient convenience and compliance. Drug delivery is aimed at altering a drug's pharmacokinetics and specificity by formulating it with different excipients, drug carriers, and medical devices. There is additional emphasis on increasing the bioavailability and duration of action of a drug to improve therapeutic outcomes. Some research has also been focused on improving safety for the person administering the medication. For example, several types of microneedle patches have been developed for administering vaccines and other medications to reduce the risk of needlestick injury.
Mesoporous silica is a form of silica that is characterised by its mesoporous structure, that is, having pores that range from 2 nm to 50 nm in diameter. According to IUPAC's terminology, mesoporosity sits between microporous (<2 nm) and macroporous (>50 nm). Mesoporous silica is a relatively recent development in nanotechnology. The most common types of mesoporous nanoparticles are MCM-41 and SBA-15. Research continues on the particles, which have applications in catalysis, drug delivery and imaging. Mesoporous ordered silica films have been also obtained with different pore topologies.
Thiolated polymers – designated thiomers – are functional polymers used in biotechnology product development with the intention to prolong mucosal drug residence time and to enhance absorption of drugs. The name thiomer was coined by Andreas Bernkop-Schnürch in 2000. Thiomers have thiol bearing side chains. Sulfhydryl ligands of low molecular mass are covalently bound to a polymeric backbone consisting of mainly biodegradable polymers, such as chitosan, hyaluronic acid, cellulose derivatives, pullulan, starch, gelatin, polyacrylates, cyclodextrins, or silicones.
In the pharmaceutical industry, drug dissolution testing is routinely used to provide critical in vitro drug release information for both quality control purposes, i.e., to assess batch-to-batch consistency of solid oral dosage forms such as tablets, and drug development, i.e., to predict in vivo drug release profiles. There are three typical situations where dissolution testing plays a vital role: (i) formulation and optimization decisions: during product development, for products where dissolution performance is a critical quality attribute, both the product formulation and the manufacturing process are optimized based on achieving specific dissolution targets. (ii) Equivalence decisions: during generic product development, and also when implementing post-approval process or formulation changes, similarity of in vitro dissolution profiles between the reference product and its generic or modified version are one of the key requirements for regulatory approval decisions. (iii) Product compliance and release decisions: during routine manufacturing, dissolution outcomes are very often one of the criteria used to make product release decisions.
Dose dumping is a phenomenon of drug metabolism in which environmental factors can cause the premature and exaggerated release of a drug. This can greatly increase the concentration of a drug in the body and thereby produce adverse effects or even drug-induced toxicity.
Rubitecan is an oral topoisomerase inhibitor, developed by SuperGen.
Mucoadhesion describes the attractive forces between a biological material and mucus or mucous membrane. Mucous membranes adhere to epithelial surfaces such as the gastrointestinal tract (GI-tract), the vagina, the lung, the eye, etc. They are generally hydrophilic as they contain many hydrogen macromolecules due to the large amount of water within its composition. However, mucin also contains glycoproteins that enable the formation of a gel-like substance. Understanding the hydrophilic bonding and adhesion mechanisms of mucus to biological material is of utmost importance in order to produce the most efficient applications. For example, in drug delivery systems, the mucus layer must be penetrated in order to effectively transport micro- or nanosized drug particles into the body. Bioadhesion is the mechanism by which two biological materials are held together by interfacial forces. The mucoadhesive properties of polymers can be evaluated via rheological synergism studies with freshly isolated mucus, tensile studies and mucosal residence time studies. Results obtained with these in vitro methods show a high correlation with results obtained in humans.
A powder is an assembly of dry particles dispersed in air. If two different powders are mixed perfectly, theoretically, three types of powder mixtures can be obtained: the random mixture, the ordered mixture or the interactive mixture.
Ciclosporin is a cyclic polypeptide that has been used widely as an orally-available immunosuppressant. It was originally used to prevent transplant rejection of solid organs but has also found use as an orally administered agent to treat psoriasis, rheumatoid arthritis, dry eye and other auto-immune related conditions. A variety of pre-clinical and clinical studies have been and are investigating its use to treat lung-related disorders via inhalation.
Lipid nanoparticles (LNPs) are nanoparticles composed of lipids. They are a novel pharmaceutical drug delivery system, and a novel pharmaceutical formulation. LNPs as a drug delivery vehicle were first approved in 2018 for the siRNA drug Onpattro. LNPs became more widely known in late 2020, as some COVID-19 vaccines that use RNA vaccine technology coat the fragile mRNA strands with PEGylated lipid nanoparticles as their delivery vehicle.
Buccal administration is a topical route of administration by which drugs held or applied in the buccal area diffuse through the oral mucosa and enter directly into the bloodstream. Buccal administration may provide better bioavailability of some drugs and a more rapid onset of action compared to oral administration because the medication does not pass through the digestive system and thereby avoids first pass metabolism.
OSU-03012 (AR-12) is a celecoxib derivative with anticancer and anti-microbial activity. Unlike celecoxib, OSU-03012 does not inhibit COX, but inhibits several other important enzymes instead which may be useful in the treatment of some forms of cancer, When combined with PDE5 inhibitors such as sildenafil or tadalafil, OSU-03012 was found to show enhanced anti-tumour effects in cell culture.
Gabapentinoids, also known as α2δ ligands, are a class of drugs that are derivatives of the inhibitory neurotransmitter gamma-Aminobutyric acid (GABA) which block α2δ subunit-containing voltage-dependent calcium channels (VDCCs). This site has been referred to as the gabapentin receptor, as it is the target of the drugs gabapentin and pregabalin.
Andreas Bernkop-Schnürch is an Austrian pharmaceutical technologist, scientist, pharmacist, entrepreneur, inventor and professor at the Institute of Pharmacy, University of Innsbruck. His research centers on the areas of pharmaceutical sciences, drug delivery, controlled release, bionanotechnology and polymer engineering. He is the inventor of various technologies such as thiolated polymers for that he coined the name thiomers in 2000 and phosphatase triggered charge converting nanoparticles for mucosal drug delivery. From 2016 to 2018 he served as a member of the Scientific Committee of the Innovative Medicines Initiative (IMI) of the European Union in Brussels giving advice on scientific priorities to be included in the Strategic Research Agenda for Horizon 2020. Since 2014 he is on the scientific advisory board of the Nicotine Science Center, Denmark. Andreas Bernkop-Schnürch is the founder of Mucobiomer Biotechnologische Forschungs- und Entwicklungs GmbH, Thiomatrix Forschungs- und Beratungs GmbH and Green River Polymers Forschungs und Entwicklungs GmbH. He is listed as a Highly Cited Researcher of the Institute of Scientific Information.
Ethosomes are phospholipid nanovesicles used for dermal and transdermal delivery of molecules. Ethosomes were developed by Touitou et al.,1997, as additional novel lipid carriers composed of ethanol, phospholipids, and water. They are reported to improve the skin delivery of various drugs. Ethanol is an efficient permeation enhancer that is believed to act by affecting the intercellular region of the stratum corneum. Ethosomes are soft malleable vesicles composed mainly of phospholipids, ethanol, and water. These soft vesicles represent novel vesicles carriers for enhanced delivery through the skin. The size of the ethosomes vesicles can be modulated from tens of nanometers to microns.
Professor Alastair J Sloan is an applied bioscientist and expert in the broad field of mineralised connective tissues, and since January 2020 current head of the Melbourne Dental School, University of Melbourne.
Protein nanotechnology is a burgeoning field of research that integrates the diverse physicochemical properties of proteins with nanoscale technology. This field assimilated into pharmaceutical research to give rise to a new classification of nanoparticles termed protein nanoparticles (PNPs). PNPs garnered significant interest due to their favorable pharmacokinetic properties such as high biocompatibility, biodegradability, and low toxicity Together, these characteristics have the potential to overcome the challenges encountered with synthetic NPs drug delivery strategies. These existing challenges including low bioavailability, a slow excretion rate, high toxicity, and a costly manufacturing process, will open the door to considerable therapeutic advancements within oncology, theranostics, and clinical translational research.
An invasome are a type of artificial vesicle nanocarrier that transport substances through the skin, the most superficial biological barrier. Vesicles are small particles surrounded by a lipid layer that can carry substances into and out of the cell. Artificial vesicles can be engineered to deliver drugs within the cell, with specific applications within transdermal drug delivery. However, the skin proves to be a barrier to effective penetration and delivery of drug therapies. Thus, invasomes are a new generation of vesicle with added structural components to assist with skin penetration.