WO2024175915A1

WO2024175915A1 - Compositions for topical administration

Info

Publication number: WO2024175915A1
Application number: PCT/GB2024/050485
Authority: WO
Inventors: Dr Hisham AL-OBAIDI
Original assignee: University Of Reading
Priority date: 2023-02-21
Filing date: 2024-02-21
Publication date: 2024-08-29
Also published as: GB202302434D0

Abstract

A composition comprising: a) an emulsion comprising: i) a eutectic mixture, and ii) an oil; and b) a biologically active agent.

Description

COMPOSITIONS FOR TOPICAL ADMINISTRATION Field of the Invention The present invention relates to a composition for the topical delivery of biologically active agents. The composition comprises an emulsion (e.g. microemulsion or nanoemulsion) comprising a eutectic mixture and an oil. Background of the Invention When used in topical applications, common medicinal or cosmetic active agents typically require a carrier in order to deliver the active agent to the intended target in the form of a composition. When used in a water-based composition, such active agents are often prone to degradation over time. Alternatively, when used in oil-based compositions, such active agents tend to be dissolved within a volatile organic solvent. However, these volatile organic solvents have several disadvantages, such as being obtained from non- renewable sources, and having low boiling points. The low boiling point means that when used in a topical application, the solvent is prone to evaporation, and often leaves behind solid deposits of the active agent on the topical application surface. Such evaporation therefore prevents effective delivery of the active agent to the topical application, as well as penetration within the topical application. It is further important to recognise the challenges of incorporating active agents such as antibiotics into stable compositions, notably due to their susceptibility to hydrolysis and photodegradation. Ensuring antibiotic stability is crucial, as exemplified by flucloxacillin, which degrades within a few hours when exposed to moisture. Other antibiotics, like erythromycin, face significant bioavailability challenges - less than 10% bioavailability due to their sensitivity to gastric acids. This issue also affects antibiotics such as phenoxymethylpenicillin, clarithromycin, and azithromycin, among others. Compounding this problem, these antibiotics often exhibit low solubility in water. In the context of topical application of active agents to the hair, such as the treatment of hair loss, a major hurdle is ensuring that treatments penetrate hair follicles effectively. Onychomycosis is an example of a fungal infection of the human nail that is commonly caused by dermatophytes, yeasts and non-dermatophytic moulds. A significant number of the global population is affected by onychomycosis causing considerable impact on the quality of life of many patients. The resistant and chronic nature of onychomycosis has been attributed to the formation of fungal biofilms. Biofilms are surface-associated microbial communities that exist within a self-secreted matrix consisting primarily of polysaccharides, proteins, nucleic acid. Biofilm structures formed by fungi may present favourable conditions for survival in the environment as well as within an infected host, and are partly responsible of recurrent/chronic (Journal of the American Academy of Dermatology, Volume 74, Issue 6, June 2016, Pages 1241-1246). Onychomycosis may present as distal subungual onychomycosis, white superficial onychomycosis, proximal subungual onychomycosis, endonyx onychomycosis and candida onychomycosis. Onychomycosis is a very difficult condition to cure. Today, it is commonly treated with an antifungal medication that is delivered to the systemic circulation, in spite of the fact that the onychomycosis infection is localized to the nail structure. This can result in serious and unwanted side effects, including gastrointestinal symptoms, liver abnormalities, rashes, taste disturbances, hypertension, and drug-drug interactions with a wide range of other medications. Topical drugs for the treatment of onychomycosis are available. However, they lack efficacy as shown in clinical data. A current product on the market (Loceryl®) is based on organic solvents (including ethanol, triacetin, butyl acetate and ethyl acetate) with amorolfine antifungal active ingredient. When the ethanol evaporates, it leaves a film of the drug within a film making polymer (typically nitrocellulose). Considering the complex structure of the nail, this film (and the antifungal compound) is very unlikely penetrate the nail bed. Loceryl® is known to have low efficacy; patients need to use the medicine for an average period of 6-12 months, and relapse rates are high. Among different antifungal drugs, griseofulvin (GF) has fungistatic effect against Trichophyton species, which are the most common cause of onychomycosis. To reach the fungal active site and produce a therapeutic effect, GF must physically adsorb to the surface of the nail. As the human nail is largely composed of keratin, with the aid of appropriate formulation approach, the binding between keratin and griseofulvin can facilitate permeation of the drug into the nail. As briefly discussed above, current topical treatments are based on dissolving the drug in a volatile solvent (typically acetone or ethanol) forming a lacquer. A layer of the drug lacquer is applied on the nail so that allowing the solvent to evaporate leaving a thin film of the drug on the nail. The hurdle of this approach is that the drug will potentially be deposited as crystals that will not be able to penetrate through the keratin network. It may also deprive the nail from its moisture content further restricting drug permeability. One potential approach to enhance efficacy is by forming viscous supersaturated solutions/ suspensions of the drugs allowing maximum concentrations reaching the fungal biofilm. Most antifungal drugs are highly hydrophobic and neutral molecules; salt formation is not possible to prepare supersaturated solutions/ suspensions. A eutectic system or eutectic mixture is a homogeneous mixture that has a melting point lower than those of the constituents. The lowest possible melting point over all of the mixing ratios of the constituents is called the eutectic temperature. A eutectic temperature is a temperature at which a mixture of two or more substances can exist in with the same proportional composition in both liquid and solid phases. A eutectic point is a point on the phase diagram describing a composition and temperature at which all of the mixture's components will melt or (assuming no supercooling or hysteresis) crystallize simultaneously from the molten state. The use of eutectic mixtures to enhance topical drug delivery is known, for example the eutectic mixture of the local anaesthetics lidocaine and prilocaine (EMLA) in US4529601. EMLA's lidocaine-prilocaine binary eutectic system is said to produce high thermodynamic activity and a high driving force for transdermal permeation of lidocaine. Although eutectic mixtures and solutions prepared from eutectic mixtures have been employed in transdermal formulations, they have been rarely if at all used in the delivery of drugs to or through the nail. WO 2011/014850 discloses a pharmaceutical composition comprising an anti-fungal agent, a eutectic agent, and a pharmaceutically acceptable low-boiling solvent, usually ethanol. The anti-fungal agent and the eutectic agent form a eutectic melt, which enhances the delivery of the anti-fungal agent or permits higher concentrations of the anti-fungal agent to be incorporated into the pharmaceutical composition. The present invention has been devised with the foregoing in mind. Summary of the Invention According to a first aspect, the invention provides a composition comprising an emulsion (e.g. microemulsion or nanoemulsion) of a eutectic mixture and an oil, and a biologically active agent (e.g. an antifungal agent). Surprisingly, compositions of the invention enable highly effective absorption of the biologically active agent. Preferably the composition comprises less than 20wt% of a volatile organic solvent, for example wherein the composition comprises no volatile organic solvent. Such compositions have been found to provide enhanced penetration compared to compositions with 20wt% or more volatile organic solvents. More preferably any amount of volatile organic solvent is 10wt% or less. Conventional volatile organic solvents, such as ethanol, typically evaporate to leave behind crystal deposits of active agent on the surface of the topical application. When deposited as solid crystals, the active is not able to penetrate into the topical application. Therefore, as the composition of the present invention does not require volatile organic solvents, the composition can therefore provide enhanced of an active agent in the topical applications, such as the skin, hair, nail, or a mucous membrane. Furthermore, as the composition of the present invention does not evaporate in the way that many conventional formulations do, the composition soothes the area to which it has been applied, and does not dry that area. The use of deep eutectic solvents (DES) as a carrier agent, minimising or avoiding the use of potentially more damaging volatile organic solvents, is more environmentally benign. The oil is an important component of the composition because it significantly increases the dispersibility of the biologically active agent within the eutectic mixture, and allows the formation of the emulsion (e.g. microemulsion/nanoemulsion) structure, thereby increasing stability and aiding penetration of the biologically active agent. Many biologically active agents will not be soluble in the eutectic mixture due to the highly polar nature of eutectic mixtures and relatively low polarity of biologically active agents. The composition of the first aspect provides a versatile emulsion system, within which a variety of different active agents can successfully be solubilised. Not only does the composition of the first aspect provide excellent solubility of the biologically active agent, the composition of the first aspect can be prepared with no, or only a small amount of, water. This prevents the degradation of water-sensitive biologically active agents, such as flucloxacillin. The compositions of the first aspect comprise an emulsion of the eutectic mixture and the oil. Emulsions are kinetically stable. The composition of the first aspect may be present as a microemulsion. Microemulsions are both kinetically and thermodynamically stable, and so do not separate out into separate phases over time. This imparts various benefits such as an enhanced shelf life and ease of storage. It can be helpful to use a surfactant to stabilise the emulsion. The Examples describe experiments showing that a variety of surfactants that can suitably be used for the claimed invention. The skilled person will be aware of many other suitable solvents. Furthermore, the composition of the first aspect has been found to be able to stably contain two biologically active agents. Therefore, the invention enables the use of two or more agents within the same formulation to increase the efficacy of a treatment. Compositions of the invention have been tested with a range of eutectic mixtures, oils, and biologically active agents. While the Examples are focussed on uses in the treatment of fungal nail infections, bacterial infections, and hair loss, it will be appreciated that the diversity of biologically active agents indicates that the compositions of the invention have broad applicability in a wide range of other topical applications. The compositions of the invention are well suited to address a common issue associated with antibiotic drug delivery. It is well known that antibiotics, such as flucloxacillin, decompose in water. The present inventors have successfully demonstrated that such antibiotics may be solubilized using the formulation of the present invention, thus providing a composition of antibacterial creams. As shown in the Examples, the antibiotic solubilized within the formulation of the present invention shows an enhanced stability in comparison to the analogous antibiotic solubilized in water. The inventors have further demonstrated that the compositions of the invention are well suited to address hair loss treatments, in particular hair loss dual treatments. The present inventors have discovered that the formulation of the present invention may form a suitable carrier for anti-hair loss medications, such as finasteride and minoxidil. A wide variety of concentrations of finasteride and minoxidil were soluble within the formulation of the present invention, allowing variable levels of topical delivery of active ingredient. According to a second aspect, the invention provides a composition according to the first aspect for use as a medicament. The present inventors have discovered a wide range of biologically active agents may be solubilised within the composition of the first aspect. Such compositions do not irritate the skin and are therefore suitable for a wide range of medicinal uses. According to a third aspect, the invention provides a composition according to the first aspect for use in a method of treatment, prevention or amelioration of a condition or disease selected from the list consisting of: a microbial infection (e.g. a fungal infection; a bacterial infection); pattern hair loss; psoriasis; foot ulcers; acne; dermatitis; wounds; warts; haemorrhoids; osteoarthritis; seborrheic dermatitis; varicose veins; and skin cancer. According to a fourth aspect, the invention provides a formulation comprising an emulsion of i) a eutectic mixture, ii) an oil. Preferably the formulation comprises less than 20wt% of a volatile organic solvent, or 10 wt% or less of volatile organic solvent, for example wherein the composition comprises no volatile organic solvent. Preferably the formulation is pharmaceutically acceptable. The formulation of the fourth aspect may be considered a carrier formulation for a biologically active agent. The formulation of the fourth aspect may be beneficially used in combination with a biologically active agent. When used in combination with an active agent, the benefits discussed in relation to the first aspect are realised in addition to those provided by the biologically active agent. According to a fifth aspect, the invention provides a method for preparing the formulation, the method comprising: i) forming a eutectic mixture of the at least one hydrogen acceptor and at least one hydrogen donor; and ii) emulsifying the eutectic mixture of step i) with an oil and a surfactant. The formulation of the fourth aspect may be obtainable (e.g. obtained) by the method of the fifth aspect. According to a sixth aspect, the invention provides a method of preparing a composition, the method comprising: i) obtaining a formulation of the fourth aspect (e.g. by performing the method of the fifth aspect); and ii) adding an active agent. The composition of the first aspect may be obtainable (e.g. obtained) by the method of the sixth aspect. According to a seventh aspect, the invention provides a method of treatment, prevention or amelioration of a disease or condition of the human or animal body comprising administering the composition of the first aspect. The diseases or conditions may be as described in relation to the third aspect. The present disclosure includes the subject-matter of the following clauses: 1. A composition comprising: a. an emulsion of i) a eutectic mixture and ii) an oil, and; b. an antifungal agent. 2. A composition according to clause 1 wherein the eutectic mixture comprises choline chloride and urea. 3. A composition according to clause 2 wherein the choline chloride and urea are present in a molar ratio of from 1:1 to 1:3, such as about 1:2. 4. A composition according to any preceding clause, wherein the oil is a naturally occurring essential oil. 5. A composition according to clause 4 wherein the oil is selected from one or more of tea tree oil, eucalyptus oil, citronella, lavender oil, cinnamon oil, peppermint oil, clove oil, thyme oil, black pepper oil, geranium oil, and coconut oil or a mixture thereof. 6. A composition according to any preceding clause wherein the oil comprises clove oil. 7. A composition according to any preceding clause, wherein the antifungal agent is griseofulvin. 8. A composition according to any preceding clause further comprising a surfactant. 9. A composition according to clause 8 wherein the surfactant is a nonionic surfactant. 10. A composition according to clause 8 or 9 wherein the surfactant is a polyethoxylated sorbitan ester, such as polyethoxylated sorbitan monooleate. 11. A composition according to any preceding clause for use as a medicament. 12. A composition according to any of clauses 1 to 10 for use in a method of treatment of a fungal infection. 13. A composition for use according to clause 12 wherein the method includes topical application of the composition to the infected area. 14. A composition according to clause 12 or 13 wherein the fungal infection is onychomycosis of the nail. 15. A composition according to any one of clauses 12 to 14 wherein the fungal infection is caused by a pathogen selected from a pathogen selected from Candida, Neoscytalidium, Scopulariopsis, Trichophyton, and Aspergillus. 16. A composition according to clause 14 or 15 wherein the onychomycosis is one of distal subungual onychomycosis, white superficial onychomycosis, proximal subungual onychomycosis, endonyx onychomycosis and candida onychomycosis. 17. A method for preparing a composition according to any one of clauses 1 to 10 comprising: i. forming a eutectic mixture; ii. emulsifying the eutectic mixture of step i with and oil and an antifungal agent. Detailed description of the Invention Weight percentages are disclosed herein are calculated with reference to the total weight of the composition unless otherwise stated. Eutectic mixture “Eutectic mixture” as used herein may refer to a homogeneous mixture that has a melting point lower than those of the constituents. Preferably, there are two constituents; however, occasionally there may be more, such as three, four or five constituents. The eutectic mixtures comprise a mixture of organic compounds including a hydrogen-bond acceptor and a hydrogen bond donor. Preferably the eutectic mixture comprises a hydrogen bond acceptor and a hydrogen bond donor. It will be appreciated that terms such as “eutectic mixture”, “eutectic solvent” and “deep eutectic solvent” are typically used interchangeably. The eutectic mixture may comprise two or more, such as three or more hydrogen-bond acceptors. The eutectic mixture may comprise two or more, such as three or more hydrogen-bond donors. Examples of hydrogen bond acceptors include quaternary ammonium salt (such as tetramethylammonium chloride, tetraethylammonium chloride, tetrabutylammonium chloride, N,N- diethyl-2-hydroxy ethanamidium chloride, N-benzyl-2-hydroxy-N,N-dimethyl ethanamidium chloride, 2-acetyl-N,N,N-trimethyl ethanamidium chloride and choline salts (such as choline chloride and acetylcholine)); amines (such as dimethylurea, urea and thiourea); amides (such as lidocaine); polyols (such as glycerol and sorbitol); carboxylic acids (such as acetic acid, propionic acid, butyric acid, valeric acid, caprolic acid, oxalic acid, malic acid benzoic acid ascetic acid, ascorbic acid, carbonic acid, citric acid, formic acid, glycolic acid, glutaric acid, lactic acid, maleic acid, malonic acid, salicylic acid); phosphonium salts (such as methyltriphenylphosphonium bromide); alcohols (such as menthol, thymol, and chloroxylenol); and betaine. Examples of hydrogen bond acceptors include choline chloride, N,N-diethyl-2-hydroxy ethanamidium chloride, tetramethylammonium chloride, methyltriphenylphosphonium bromide, tetrabutylammonium chloride, N-benzyl-2-hydroxy-N,N- dimethyl ethanamidium chloride, tetraethylammonium chloride, and 2-acetyl-N,N,N-trimethyl ethanamidium chloride. Choline salts, especially choline chloride, are preferred hydrogen bond acceptors. Preferably the hydrogen bond acceptor is a quaternary ammonium salt (such as a choline salt) and/or an amine (such as urea). Other preferred hydrogen bond acceptors are urea and glutaric acid. Examples of hydrogen bond donors are alcohols (such as phenol, menthol, thymol, chloroxylenol dodecanol, polyols (such as glycerol and sorbitol); sugars (such as fructose, glucose, sucrose, xylose) and diols (such as ethylene glycol, 1,2-propanediol, 1,4-butanediol, resorcinol)); amino acids (such as arginine, glycine, lysine, proline and serine); amines (such as dimethylurea, urea, thiourea); amides (such as acetamide, benzamide, niacinamide); nitrogen containing heterocyclic compounds (such as imidazole); and carboxylic acids (such as acetic acid, propionic acid, butyric acid, valeric acid, caprylic acid, oxalic acid, malic acid and benzoic acid ascetic acid, ascorbic acid, carbonic acid, citric acid, formic acid, glycolic acid, glutaric acid, lactic acid, maleic acid, malonic acid, salicylic acid). Examples of hydrogen bond donors include urea, thiourea, acetamide, benzamide, glycerol, imidazole, malonic acid and glucose. Glycolic acid, glutaric acid, acetic acid, glycerol and urea are preferred hydrogen bond donors. Urea is a preferred hydrogen bond donor. Urea is known as a topical emollient, moisturizer, keratolytic agent, and antipruritic. Various deep eutectic solvents (DESs) were demonstrated using urea combined with environmentally benign and biocompatible substances such as glycolic acid (noted for its keratolytic effects), glycerol, and choline chloride. Urea and glycolic acid each possess keratolytic properties. Therefore, the use of urea and/or glycolic acid may be particularly preferable for enhancing penetration of biologically active agents (e.g. antifungal agents), for example into the skin and/or nail. It will be appreciated that the hydrogen bond donor should be different from the hydrogen bond acceptor. Some specific embodiments of eutectic mixtures useful for the instant invention are the following: Phenol/Menthol; Phenol/Choline chloride; Phenol/Choline chloride/Urea; Choline chloride/Urea; Betaine hydrochloride or Choline chloride/Urea; Resorcinol/Choline chloride; BHT/Choline chloride; Chloroxylenol/Choline chloride/Menthol; Choline chloride/Citric acid monohydrate; Choline chloride/Arginine/Urea; Choline chloride/Niacinamide/Urea; Camphor/Menthol; Camphor/Menthol/Lauryl alcohol; mono laurate/Menthol; Terbinafine hydrochloride/lidocaine. Other suitable eutectic mixtures include: Urea/Glycolic acid; Urea/Glycerol; Choline chloride/Glutaric acid; Choline chloride/Acetic acid; Choline chloride/Glycerol; Glutaric acid/Glycerol. For each pair of hydrogen bond donors/hydrogen bond acceptors, the skilled person will be aware that the appropriate ratio will differ depending on the freezing point depression to be achieved. For example, in the case of choline chloride/urea, the eutectic point is achieved at a choline chloride: urea ratio of 1:2, such as a molar ratio. The eutectic formed between choline chloride and urea is preferred in the compositions of the invention, and ratios of between 1:3 and 1:1, such as a molar ratio may be successfully employed. The molar amount of hydrogen bond donor, relative to the molar amount of hydrogen bond acceptor, may be 10% or more, such as 20% or more, preferably 30% or more, or 50% or more, such as 80% or more, or 90% or more, or 100% or more, such as 150% or more, or 200% or more. The molar amount of hydrogen bond donor, relative to the molar amount of hydrogen bond acceptor, may be 1000% or less, such as 800% or less, such as 500% or less, preferably 300% or less, or 200% or less, such as 150% or less, or 120% or less, for example 100% or less. The molar amount of hydrogen bond donor, relative to the molar amount of hydrogen bond acceptor, may be from 10% to 1000%, such as from 30% to 300%, or from 50% to 200%. The composition and/or the formulation may comprise the eutectic mixture in an amount, by weight, relative to the total weight of the composition and/or formulation, of 1% or more, such as 2% or more, preferably 5% or more, or 8% or more, such as 10% or more, or 15% or more, such as 20% or more, for example 25% or more, or 30% or more, or 35% or more. The composition and/or the formulation may comprise the eutectic mixture in an amount, by weight, relative to the total weight of the composition and/or formulation, of 80% or less, or 70% or less, preferably 60% or less, or 50% or less, such as 45% or less, or 40% or less, for instance 35% or less, or 30% or less, such as 25% or less. The composition and/or the formulation may comprise the eutectic mixture in an amount, by weight, relative to the total weight of the composition and/or formulation, of from 1 to 80%, such as from 5 to 60%, or from 8 to 50%. Oil “Oil” as used herein may refer to a nonpolar substance that is substantially immiscible with water and is a liquid at 20°C. The oil may be a hydrocarbon. The oil may contain carbon atoms, hydrogen atoms, and optionally oxygen atoms. Suitable oils may be animal, vegetable, or in nature. Preferably, the oil is a naturally occurring oil, and may be vegetable in nature. In a preferred embodiment, the oil comprises an essential oil. “Essential oil” as used herein may refer to a concentrated hydrophobic liquid containing volatile chemical compounds from plants. Preferred essential oils are tea tree oil, eucalyptus oil, citronella, lavender oil, cinnamon oil, peppermint oil, clove oil, thyme oil, black pepper oil, geranium oil, and coconut oil or a mixture thereof. Clove (Syzygium aromaticum) oil, tea tree oil, rosemary oil, olive oil, or mixtures thereof are particularly preferred, and encompasses bud oil, leaf oil and stem oil varieties of clove oil. The oil may comprise component oils that are terpenes or terpenoids. Tea tree oil typically comprises terpinen-4-ol, γ-terpinene, 1,8-cineole, α-terpinene, α-terpineol, p-cymene, and/or α-pinene. Rosemary oil typically comprises 1,8-cineol, camphor, α-pinene, limonene, camphene and/or linalool. Clove oil typically comprises eugenol, eugenyl acetate, β-caryophyllene, and/or α-humulene. Preferably the oil comprises terpenes and/or terpenoids (such as those selected from the lists above) in an amount of 40 wt% or more, such as 60 wt% or more, or 80 wt% or more, for example 90 wt% or more, such as from 40 to 99.99 wt%, or from 60 to 99.5 wt%. The oil may comprise component oils that are fatty acids and/or fatty alcohols. Vegetable oils tend to comprise significant amounts of fatty acids. Olive oil typically comprises oleic acids, linoleic acid, stearic acid, α-linolenic acid and/or palmitic acid. Shea butter typically comprises palmitic acid, stearic acid, oleic acid, linoleic acid, and/or arachidic acid. Jojoba oil typically comprises fatty acids such as eicosenoic acid, erucic acid, and/or oleic acid, and fatty alcohols such as cis-11-eicosenol, cis-13- docosenol, and/or cis-15-tetracosenol. Other suitable oils include argan oil, baobab oil, castor oil, coconut oil, hemp seed oil and sesame oil. The oil may comprise fatty acids (such as those selected from the lists above) in an amount of 40 wt% or more, such as 60 wt% or more, or 80 wt% or more, for example 90 wt% or more, such as from 40 to 99.99 wt%, or from 60 to 99.5 wt%. The oil may be selected from soybean oil, rapeseed oil, canola oil, sunflower oil, safflower oil, peanut oil, cottonseed oil, and tropical oils, such as coconut oil, palm oil, and rice bran oil. The oil may be a mixture of substances. Preferably the oil comprises fatty acids, terpenes and/or terpenoids (such as those selected from the lists above) in an amount of 40 wt% or more, such as 60 wt% or more, or 80 wt% or more, for example 90 wt% or more, such as from 40 to 99.99 wt%, or from 60 to 99.5 wt%. The composition and/or the formulation may comprise the oil in an amount, by weight, relative to the total weight of the composition and/or formulation, of 1% or more, such as 2% or more, preferably 5% or more, or 8% or more, such as 10% or more, or 15% or more, such as 20% or more, for example 25% or more, or 30% or more, or 35% or more. The composition and/or the formulation may comprise the oil in an amount, by weight, relative to the total weight of the composition and/or formulation, of 95% or less, preferably 90% or less, or 85% or less, such as 80% or less, or 70% or less, such as 60% or less. The composition and/or the formulation may the oil in an amount, by weight, relative to the total weight of the composition and/or formulation, of from 1 to 95%, such as from 5 to 90%, or from 8 to 85%. Surfactant In some embodiments, the compositions of the invention comprise a surfactant. The surfactant serves inter alia to stabilise the emulsion. Anionic, cationic and non-ionic surfactants are suitable in this context. Non-ionic surfactants are preferred. While it is appreciated that some oils, especially fatty acid and/or fatty ester based oils, can act as surfactants, it will be understood that the surfactant should be different from the oil. The composition may be emulsified, for example to prepare a cream, with an oil phase and a surfactant. A particularly preferred class of surfactants fatty acid esters of ethoxylated sorbitan, having the general structure (I): (I)

wherein x, y, z and w are independently selected integers (e.g. from 1 to 10), and R is a hydrocarbon, preferably CH3−(CH2)7−CH=CH−(CH2)7−. Preferably, x+y+z+w is 20. Such examples of polyethoxylated sorbitan monooleate include those available under the trade name Span, such as Span 80 (CAS 1338-43-8) or Span 20 (CAS 1338-39-2). A particularly preferred surfactant is sorbitan monooleate polysorbate 80 (II): (II)

A particularly preferred class of surfactant are polyoxyethylene ethers, such as those available under the trade name Brij, such as Brij 97 (CAS 9004-98-2) having the formula C₁₈H₃₅-O-(CH₂CH₂)_xH, where x is about 10 on average (mean), such as from 8 to 12. A particularly preferred class of surfactant are block copolymers, such as an ethylene oxide and propylene oxide block copolymer. For example, those available under the trade name Pluronic, such as Pluronic L-611 (CAS 9003-11-6). Examples of suitable surfactants include cetearyl alcohol, stearic acid, lauryl alcohol, glyceryl behenate, carnauba wax, beeswax, and candelilla wax. The composition and/or the formulation may comprise the surfactant in an amount, by weight, relative to the total weight of the composition and/or formulation, of 0.1% or more, or 1% or more, preferably 2% or more, or 5% or more, or 8% or more, such as 10% or more, or 15% or more, such as 20% or more, for example 25% or more. The composition and/or the formulation may comprise the surfactant in an amount, by weight, relative to the total weight of the composition and/or formulation, of 80% or less, or 60% or less, or 50% or less, preferably 40% or less, for instance 35% or less, or 30% or less, such as 25% or less, or 20% or less. The composition and/or the formulation may comprise the surfactant in an amount, by weight, relative to the total weight of the composition and/or formulation, of from 0.1 to 80%, such as from 2 to 40%, or from 8 to 40%.Surfactant may be present in an amount of from 1% to 20% by weight based on the weight of the composition, preferably from 2% to 10%. Biologically Active Agent The composition of the invention comprises a biologically active agent. The biologically active agent may be a medicament and/or a cosmetic active ingredient. Such a medicament may be therefore considered a pharmaceutical active agent. There is one or more active agents present in the such as two or more active agents. The biologically active agent may be an antimicrobial agent, such as an antifungal, antibacterial and/or antiviral agent. Preferably the biologically active agent is an antifungal and/or antibacterial agent. “Antifungal agent" as used herein may include a compound that has the ability to kill, to stop the growth, or to slow the growth of a fungus in vitro or in vivo as well as a compound that can prevent or alleviate a fungal infection in vitro or in vivo. The anti-fungal agent may be a member of the classes of azoles (including imidazoles and triazoles) such as miconazole, ketoconazole, clotrimazole, econazole, bifonazole, butoconazole, fenticonazole, isoconazole, oxiconazole, sertaconazole, sulconazole, tioconazole, itraconazole, fluconazole, voriconzole, terconazole, isavuconazole, ravuconazole, and posaconazole; polyenes such as natamycin, rimocidin, filipin, nystatin, candicidin, nystatin, candicidin, and amphoteracin B; thiazoles such as abafungin; echinocandins; allylamines such as terbinafine, amorolfine, naftifine, and terbinafine; thiocarbamates such as tolnaftate; phenolic compounds such as haloprogin; pyridones such as ciclopirox olamine; and miscellaneous antifungal agents such as undecylenic acid. The antifungal agent may be an allylamine anti-fungal agent. In a more preferred embodiment, the allylamine anti-fungal agent is selected from the group consisting of amorolfine, butenafine, naftifine, terbinafine, and a pharmaceutically acceptable salt thereof. In an even more preferred embodiment, the allylamine anti-fungal agent is terbinafine or a pharmaceutically acceptable salt thereof. Griseofulvin is a particularly preferred antifungal agent. Clotrimazole and terbinafine, or combinations thereof are also particularly preferred antifungal agents. The composition may comprise two or more antifungal agents. The structure of clotimazole is:

The structure of terbinafine is:

The structure of griseofulvin is:

Preferably, the antifungal agent is present in the composition in an amount of between 1% and 10% based on the weight of the composition. “Antibiotic agent" as used herein may include a compound that has the ability to kill, to stop the growth, or to slow the growth of a bacteria in vitro or in vivo as well as a compound that can prevent or alleviate a bacterial infection in vitro or in vivo. The biologically active agent may be an antibiotic that is a penicillin (such as phenoxymethylpenicillin, flucloxacillin, amoxycillin), a macrolide (such as clarithromycin, azithromycin, erythromycin), a cephalosporin (such as cefaclor, cefadroxil and cefalexin), and/or a tetracycline (such as tetracycline, doxycycline and lymecycline). The biologically active agent may be an anti-hair loss agent. The anti-hair loss agent may be finasteride, minoxidil, and/or ketoconazole. The structure of finasteride is:

The structure of minoxidil is: The biologically active agent may be a

agent, such as vitamin D or an analogue thereof (e.g. alfacalcidol, calcipotriol (calcipotriene), doxercalciferol, falecalcitriol, paricalcitol, tacalcitol), a corticosteroid, calcineurin inhibitors such as tacrolimus and pimecrolimus, coal tar, dithranol. The biologically active agent may be an ulcer treatment agent, such as a diabetic foot ulcer treatment agent. Examples of ulcer treatment agent, such as a diabetic foot ulcer treatment agent may be growth factors, silver nanoparticles, or combinations thereof. The biologically active agent may be an acne treatment agent, such as an acne vulgaris treatment agent. Examples of acne treatment agent, such as acne vulgaris treatment agent may be salicylic acid or derivatives thereof (e.g. acetyl salicylic acid, sodium salicylate, sulfasalazine, and diflunisal), benzoyl peroxide or derivatives thereof, retinoids such as retinoic acids or tretinoin, azelaic acid and derivatives thereof (e.g. dilaurylazelate ester, potassium azeloyl diglycinate), or combinations thereof. The biologically active agent may be a dermatitis treatment agent, such as an atopic dermatitis treatment agent. Examples of dermatitis treatment agent, such as atopic dermatitis treatment agent may be emollients, topical corticosteroids, cyclosporine, calcineurin inhibitors (such as tacrolimus and pimecrolimus), crisaborole, ruxolitinib, and/or hydrating agents (such as hyaluronic acid). The biologically active agent may be a burn wound treatment agent. Examples of burn wound treatment agent may be aloe vera extract, honey, silver sulfinamide, mafenide, and/or chlorhexidine. The biologically active agent may be a wart treatment agent. Examples of wart treatment agent may be keratolytic agents such as salicylic acid, urea, and/or alpha-hydroxy acids. The biologically active agent may be a haemorrhoid treatment agent. Examples of haemorrhoid treatment agent may be an anti-inflammatory and/or analgesic drug such as ibuprofen, naproxen, diclofenac, celecoxib, mefenamic acid, etoricoxib, indomethacin, and/or aspirin. The biologically active agent may be an osteoarthritis treatment agent. Examples of osteoarthritis treatment agent may be a non-steroidal anti- drug (NSAID), such as diclofenac, ibuprofen, naproxen, celecoxib, and/or rofecoxib. The biologically active agent may be a dermatitis treatment agent, such as a seborrheic dermatitis treatment agent. Examples of dermatitis treatment agent, such as a seborrheic dermatitis treatment agent, may be an antifungal agent such as clotrimazole, econazole, miconazole, terbinafine, fluconazole, ketoconazole, nystatin and/or amphotericin. The biologically active agent may be a varicose vein treatment agent. Examples of varicose vein treatment agent may be venotonic agents such as escin and/or a flavonoid. The biologically active agent may be an anti-cancer agent. Examples of anti-cancer agent may be chemotherapeutic drugs and/or immune response modifier. The biologically active agent may be an anti-inflammatory agent. Examples of anti-inflammatory agent may be ibuprofen, naproxen, diclofenac, celecoxib, mefenamic acid, etoricoxib, indomethacin, and/or aspirin. The biologically active agent may be a cosmetic active ingredient, such as an alpha hydroxy acid (such as glycolic acid and lactic acid), benzoyl peroxide, a beta hydroxy acid (such as salicylic acid), ceramides, hyaluronic acid, hydroquinone, vitamin A or an analogue thereof (e.g. retinoic acid), vitamin C or an analogue thereof (e.g. dehydroascorbic acid, ascorbyl phosphate, sodium ascorbate, calcium ascorbate, zinc ascorbate, niacinamide ascorbate), and/or niacinamide. The biologically active agent may be a salt, solvate and/or prodrug (e.g. ester) of one of the compounds mentioned herein, for example a pharmaceutically acceptable salt, solvate and/or prodrug (e.g. ester) of one of the compounds mentioned herein. The composition and/or the formulation may comprise the biologically active agent in an amount, by weight, relative to the total weight of the composition and/or formulation, of 0.001 wt% or more, such as 0.01 wt% or more, preferably 0.1 wt% or more, for example 0.2 wt% or more, or 0.5 wt% or more, or 1 wt% or more, or 2 wt% or more, such as 3 wt% or more, or 4 wt% or more. The composition and/or the formulation may comprise the biologically active agent in an amount, by weight, relative to the total weight of the composition and/or formulation, of 30 wt% or less, such as 20 wt% or less, or 15 wt% or less, preferably 10 wt% or less, such as 8 wt% or less, or 6 wt% or less, for example 5 wt% or less. The composition and/or the formulation may comprise the biologically active agent in an amount, by weight, relative to the total weight of the composition and/or formulation, of from 0.001 to 30 wt%, such as from 0.1 to 10 wt%, or from 0.5 to 6 wt%. Emulsion “Emulsion” as used herein may refer to a colloidal mixture of two or more liquids that are immiscible owing to liquid-liquid phase separation. Emulsions comprise a dispersed and continuous phase; one liquid (the dispersed phase) is dispersed in the other (the continuous phase). In the present invention it may be that either the eutectic mixture forms the continuous phase and the oil the dispersed phase, or alternatively the oil forms the continuous phase and the eutectic mixture the dispersed phase. Preferably, the emulsions used in the compositions of the invention are stable, and resist flocculation, coalescence, creaming, and sedimentation or other forms of instability for extended periods, such as more than one day, more than one week, more than two weeks, more than one month, or more than one year. Preferably, the emulsions comprise eutectic mixture and oil in a ratio ranging from 1:20 to 20:1 w/w. Advantageously, the ratio is between 20:1 and 3:1 w/w. The formulation and/or composition may contain the eutectic mixture in an amount, relative to the amount of oil, by weight, of 1% or more, such as 2% or more, or 5% or more, preferably 10% or more, such as 15% or more, or 20% or more, or 25% or more. The formulation and/or composition may contain the eutectic mixture in an amount, relative to the amount of oil, by weight, of 400% or less, such as 300% or less, or 200% or less, preferably 150% or less, or 120% or less, such as 100% or less, or 80% or less. The formulation and/or composition may contain the eutectic mixture in an amount, relative to the amount of oil, by weight, of from 1 to 500%, such as from 10 to 150%. The emulsion will generally require stirring in order to form, which may be achieved by any method known per se in the art. Preferably, the emulsion contains little or no water, i.e. it is essentially nonaqueous. Preferably, the amount of water is below 5 %, more preferably below 1 %, most preferably below 0.1 % w/w. Sensitivity to water may depend on the biologically active agent being used in the formulation and/or composition. The formulation and/or composition may contain water in an amount of 10 wt% or less, such as 5 wt% or less, or 2 wt% or less, preferably 1 wt% or less, for example 0.1 wt% or less, or 0.001 wt% or less, for example wherein there is no water in the formulation and/or composition. Most preferably the formulation and/or composition contains no water, although it will be understood that traces of water may not significantly affect the function of the formulation and/or composition. The formulation may be an emulsion (e.g. microemulsion) with an average (mean, e.g. number average) particle size (diameter) of 200nm or less, such as 150nm or less, preferably 100nm or less, for example 80nm or less, or 60 nm or less, such as 50nm or less or 45nm or less. The average particle size of the formulation may be 5nm or more, such as 10nm or or 20nm or more, for example 30nm or more, or 40nm or more. The average particle size of the may be from 5 to 200nm, such as from 20 to 100nm, or from 30 to 60nm. The polydispersity index (PDI) of the formulation may be 0.05 or more, such as 0.1 or more, or 0.15 or more, such as 0.18 or more, or 0.19 or more. The PDI of the formulation may be 0.3 or less, such as 0.25 or less, or 0.22 or less, for example 0.20 or less, or 0.195 or less. The PDI of the formulation may be from 0.05 to 0.3, such as from 0.18 to 0.20. The composition may be an emulsion (e.g. microemulsion) with an average (mean, e.g. number average) particle size (diameter) of 400nm or less, such as 300nm or less, or 200nm or less, for example 160nm or less, or 140nm or less, such as 120nm or less, or 110nm or less, such as 100nm or less. The average particle size of the composition may be 10nm or more, such as 20nm or more, or 40nm or more, or 60nm or more, such as 80nm or more, or 90nm or more, such as 95nm or more. The average particle size of the composition may be from 10 to 400nm, such as from 40 to 200nm, or from 80 to 120nm. The polydispersity index of the composition may be 0.1 or more, or 0.15 or more, such as 0.20 or more, or 0.22 or more, such as 0.24 or more. The PDI of the formulation may be 0.4 or less, such as 0.35 or less, or 0.30 or less, for example 0.28 or less, or 0.26 or less. The PDI of the formulation may be from 0.1 to 0.4, such as from 0.20 to 0.30. Particle size and polydispersity index may be determined dynamic light scattering, for example using a Zetasizer Nano-ZS (Malvern, UK). In certain embodiments, the emulsion may be a microemulsion. Such a microemulsion system is both kinetically and thermodynamically stable and does not separate out into separate phases. This imparts various benefits such as an enhanced shelf life and ease of storage. The composition and the formulation of the invention are preferably liquids. Preferably the composition and the formulation of the invention do not include solid materials. Volatile organic solvent Preferably the composition and/or the formulation comprises less than 20wt% of a volatile organic solvent, for example wherein the composition and/or the formulation comprises no volatile organic solvent. Such compositions and/or formulations have been found to provide enhanced penetration compared to compositions and/or formulations with 20wt% or more volatile organic solvents. More preferably any amount of volatile organic solvent is 10wt% or less. The amount of any given volatile organic solvent be less than 20wt%, or there may be none of a given volatile organic solvent (e.g. ethanol and/or acetate). The total combined amount of volatile organic solvents is less than 20wt%, or there may be no volatile organic solvent in the formulation or composition. Preferably the volatile organic solvent is ethanol and/or ethyl acetate. The volatile organic solvent may be acetone, ethyl acetate, and/or ethanol, or the like. The volatile organic solvent may be an alcohol (for example methanol, ethanol, propanol (e.g. isopropanol, n-propanol), butanol (e.g. tert-butanol)) and/or a polar aprotic solvent (such as ethyl acetate, acetone, acetonitrile). The conventional volatile organic solvent may include a nonpolar solvent, such as a nonpolar hydrocarbon solvent (such as pentane, cyclopentane, hexane, cyclohexane, heptane, benzene and toluene); a nonpolar ether solvent (such as diethyl ether, 1,4-dioxane, methyl tert-butyl ether, glyme, and tetrahydrofuran); a polar aprotic solvent (such as ethyl acetate, acetone and acetonitrile); a polar protic solvent (such as alcohols, for example methanol, ethanol, propanol (e.g. isopropanol, n- propanol), butanol (e.g. tert-butanol)), and a carboxylic acid (such as acetic acid and formic acid). The volatile organic solvent(s) may be pharmaceutically acceptable (e.g. ethanol). The volatile organic solvent(s) may be those having a boiling point of 150°C or less, such as 120°C or less, such as 105°C or less, or 100°C or less, for example 90°C or less, or 85°C or less, such as 80°C or less (at atmospheric pressure, 101kPa). The composition may comprise 50 wt% of a volatile organic solvent (e.g. ethanol and/or ethyl acetate) or less, such as 40 wt% or less, or 30 wt% or less, or 25 wt% or less. The composition preferably comprises 20 wt% of a volatile organic solvent (e.g. ethanol and/or ethyl acetate) or less, such as 18 wt% or less, or 15 wt% or less, or 14 wt% or less, for example 12 wt% or less, or 10 wt% or less, for example 5 wt% or less, or 4 wt% or less, such as 3 wt% or less, or 2 wt% or less, such as 1 wt% or less or 0.1 wt% or less. Preferably the composition includes no volatile organic solvent (e.g. ethanol and/or ethyl acetate). However, it will be understood that trace or low amounts of volatile organic solvents may still allow the composition/formulation to be effective. The composition may comprise a volatile organic solvent (e.g. ethanol and/or ethyl acetate) in an amount of from 0.0001 to 50 wt%, preferably from 0.0001 to 20 wt%, or from 0.01 to 20 wt%, such as from 0.01% to 10%. Administration The compositions of the current invention may be for topical administration. As such the compositions of the current invention may be for administration to the skin, nail, hair, and/or a mucous membrane (such as the conjunctiva, nasal mucosa, olfactory mucosa, oral mucosa, penile mucosa, vaginal mucosa, frenulum of the tongue and/or anal canal). Compositions and/or formulations of the may suitably be provided in a suitable form for a user to apply topically. For instance, the compositions and/or formulations may be provided in a tube, pump (e.g. metered pump), dropper, or vial. It is preferred that compositions of the invention are formulated as creams for administration to the skin, and formulated as liquids for administration to nail(s). In certain preferred embodiments, the compositions of the current invention have the advantage of containing high concentrations of low-solubility or hard-to formulate drugs such as griseofulvin. Such concentrated compositions may be of particular benefit in treatment of chronic diseases of the nail or other difficult-to-treat areas of the body (e.g., onychomycosis) because the high concentrations can 1) increase the effective concentration of drug in the affected area and/or 2) improve retention of the drug at or near the affected area. Although the compositions of the invention may be used to treat various diseases and disorders of the skin or mucous membranes, they are most advantageously used to treat conditions involving the nails of the hands or feet. Compositions of the invention can also treat various diseases and conditions of the hair and nails. The compositions and methods of the invention provide increased penetration of the active agent, such as an antifungal agent, in the composition into and through the nail and to the nail bed. The compositions of the invention may be used effectively to treat diseases and disorders in humans or in other animals, such as cats, dogs, horses, cattle, sheep, goats, pigs, and birds. In human and in veterinary patients, the compositions of the invention may be used, depending on the particular animal treated, to treat conditions involving nails, hooves, horns, or beaks. The compositions of the invention are especially well suited for the treatment of diseases such as onychomycosis and other disorders of the nail and nail bed. The composition is topically applied to the surface of the nail and surrounding tissue by any means by which the composition may be applied. The method of application may vary depending on the viscosity of the composition. Thus, for example, the composition may be rubbed, painted, dabbed, dripped, sprayed, wiped, spread, or poured onto the affected nail and surrounding tissues, or utilized as a soak. Frequency of treatment and duration of therapy will vary depending on several factors, including the condition that is being treated, the identity and concentration of the antifungal agent in the composition, and constituents of the composition other than the antifungal agent. Typically, the frequency of treatment will be twice daily to once weekly, and preferably once daily. The composition may be for administration at a regular interval, such as biweekly or more frequently, or weekly or more frequently, such as every two days or more frequently, or every day or more frequently. The composition may be for administration at a regular interval of three times a day or less frequently, such as twice a day or less frequently, for example daily or less frequently, or every two days or less frequently. The may be for administration at a regular interval of from three times a day to biweekly, such as two times a day to every two days. The preferred duration of topical treatment is at least 36 weeks and preferably longer, such as 40 weeks or 48 weeks. The preferred criterion for treatment efficacy is complete cure, which can be assessed at the end of treatment, but is preferably assessed 4 to 12 weeks after the end of treatment, most preferably 4 weeks after the end of treatment. Optional additives The composition and/or formulation may comprise additives. Optionally, the composition comprises at least one pharmaceutically acceptable thickener, or film-forming agent. Preferably the composition comprises at least one thickener, or film forming agent. In certain preferred embodiments, the thickener is selected from the group consisting of a cellulose polymer, a carbomer, a polyvinyl pyrrolidone, a polyvinyl alcohol, a poloxamer, a xanthan gum, a locust bean gum, a guar gum and mixtures thereof. Preferably, the formulation includes a cellulosic thickener. Suitable cellulosic thickeners include, but are not limited to, hydroxypropyl cellulose (HPC) of various grades, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, hydroxyethyl methyl cellulose, ethyl cellulose, methyl cellulose, carboxymethyl cellulose, dextran, guar gum, pectin, starch, cellulose, and the like. Film forming agents can be selected from the group comprising of polyvinyl pyrrolidone, hydroxypropyl methyl cellulose, acacia, alginate derivatives (e.g. as disclosed by Pawar et al., Biomaterials, 2012, 33 (11), pages 3279-3305), hydroxy propyl cellulose, carboxymethylcellulose sodium, compressible sugar, ethyl cellulose, gelatin, liquid glucose, methyl cellulose, pregelatinized starch and other materials known to one of ordinary skill in the art. Film forming agents may be present in the composition in the range of from 1 % to 10 % by weight. The composition may be a pharmaceutically acceptable. The composition may be formulated as a cream, gel, lotion, spray, paste, balm, and/or wax. The composition and/or formulation may comprise additives in an amount of 40 wt% or less, such as 30 wt% or less, or 20 wt% or less, preferably 10 wt% or less, such as 5 wt% or less. The composition and/or formulation may comprise additives in an amount of 0.01 wt% or more, such as 0.1 wt% or more. The composition and/or formulation may comprise additives in an amount of from 0.01 wt% to 40 wt%, such as from 0.01 wt% to 10 wt%. Preparation of the formulation The eutectic mixture may be formed by mixing) at least one hydrogen bond donor and at least one hydrogen bond acceptor. The at least one hydrogen bond donor and at least one hydrogen bond acceptor may be heated, until a homogenous clear liquid is obtained. This homogeneous liquid may be termed the first homogeneous clear liquid. The eutectic mixture may be heated using suitable heating apparatus that would be apparent to the skilled person, for example, a water bath or a hot plate. The skilled person would understand that the eutectic mixture would need to be heated to a suitable temperature which is lower than the melting points of either component of the eutectic mixture. For example, the eutectic mixture may be heated up to at least 50°C, at least 60°C, at least 70°C, for example from 50 to 80°C. The eutectic mixture may be agitated to obtain a first homogeneous clear liquid. Such agitation may be continuous, or intermittent throughout the step of forming a eutectic mixture. Preferably, such agitation is continuous throughout the step of forming a eutectic mixture. Upon forming the first homogeneous liquid, a surfactant may be added. The first homogeneous liquid and surfactant may then be heated, until a homogenous clear liquid is obtained. This homogeneous liquid may be termed the second homogeneous clear liquid. The first homogeneous liquid and surfactant may be heated using suitable heating apparatus that would be apparent to the skilled person, for example, a water bath or a hot plate. The first homogeneous liquid and surfactant may be heated up to at least 40°C, such as at least 50°C, for example from 40 to 80°C. The first homogeneous liquid and surfactant may be agitated to obtain a second homogeneous clear liquid. Such agitation may be continuous or intermittent. Preferably, such agitation is continuous throughout the step of mixing the first homogeneous liquid and surfactant. Upon forming the second homogenous clear liquid, the second homogeneous clear liquid comprising eutectic mixture and surfactant may be (e.g. gradually) combined with the oil. Such addition of the second homogeneous clear liquid into the oil may be added in portions, such as dropwise addition. Such addition of the second homogeneous clear liquid into the oil may be added at once. Such addition of the second homogeneous clear liquid into the oil is preferably added in portions, such as dropwise addition. The second homogeneous liquid and oil may be heated using suitable heating apparatus that would be apparent to the skilled person, for example, a water bath or a hot plate. The second homogeneous clear liquid and oil may be heated up to at least 40°C, such as at least 50°C (e.g. from 40 to 80°C). The second homogeneous clear liquid and oil may be agitated. Such agitation may be continuous or intermittent. Preferably, such agitation is continuous throughout the step of mixing the second homogeneous clear liquid and oil. Following addition of the second homogeneous clear liquid to the oil, the emulsion will be formed. The emulsion may be maintained at the same used during the step of mixing the second homogeneous clear liquid and oil for at least 5 such as at least 10 minutes. After this, the temperature may be allowed to return to room temperature (i.e., from 15 to 25°C) and may be agitated continuously or intermittently for at least 6 hours, such 6 to 12 hours, 8 to 10 hours. Such conditions may be considered environmentally friendly, as the formulation may be formed at relatively low temperatures or requiring the use of harsh reagents. Preparation of the composition The composition may be prepared by providing/obtaining the formulation of the invention, and then adding a biologically active agent. Obtaining the formulation may include directly carrying out the method described above to obtain the formulation, or otherwise obtaining the formulation. The formulation and biologically active agent may be blended together. The formulation and active agent may be agitated. Such agitation may be continuous or intermittent. Preferably, such agitation is continuous throughout the step of blending the formulation and active agent. The formulation and biologically active agent may be blended together at room temperature (i.e. from 15 to 25°C). The formulation and biologically active agent may be blended together at a temperature higher than room temperature, such as heated up to at least 50°C, at least 60°C, at least 70°C (e.g. from 50°C to 90°C). Where the formulation and active agent are blended together at a temperature higher than room temperature, the formulation and active agent may be heated using suitable heating apparatus that would be apparent to the skilled person, for example, a water bath or a hot plate. The formulation and biologically active agent may be blended together for at least one hour, at least 2 hours, at least 6 hours. The formulation and biologically active agent may be blended together for up to 12 hours, up to 8 hours, up to 4 hours, or up to 2 hours. The formulation and biologically active agent may be blended together from 6 to 12 hours, such as 8 to 10 hours. The composition generally comprises the formulation and the biologically active agent. The composition may be suitable for topical application. Additives may be added to the composition prior to topical application. Such additives may be pharmaceutically acceptable thickeners or film-forming agents. Alternatively, the composition may be emulsified with a pharmaceutically acceptable oil and surfactant to produce a pharmaceutically acceptable product, such as a cream, gel, lotion, spray, paste, balm or wax. Such conditions may be considered friendly, as the composition may be formed relatively low temperatures, without requiring reagents. Veterinary applications The compositions of the current invention may be used to treat topical disorders of mammalian subjects, such as humans, or non-mammalian subjects. The compositions may be used to treat veterinary subjects. Veterinary subjects include domesticated companion animals, animals farmed for food, and working animals. Examples of domesticated companion animals include cats, dogs, rabbits, ferrets, pigs, rodents such as gerbils, hamsters, chinchillas, rats, mice, guinea pigs, birds such as parrots, passerines and fowls, reptiles such as turtles, lizards, snakes, iguanas, amphibians such as frogs and salamanders. Examples of animals farmed for food include mammals such as sheep, cows, pigs, goats, and birds such as turkeys, chickens, ducks, geese, quail, pigeon, guineafowl, ostrich, and emus. Examples of working animals include horses, donkeys, camels, oxen, dogs. For instance, compositions of the invention incorporating antifungal agents such as clotrimazole could be used to treat dermatophytosis (ringworm). Compositions comprising a corticosteroid and/or cyclosporine may be used to treat the allergic skin condition atopic dermatitis in animals such as dogs. Compositions comprising antimicrobial (e.g. antibiotic) agents, silver nanoparticles or other healing agents may assist with the healing of wounds, such as cuts or surgical wounds, for animals including larger animals such as horses and livestock. The compositions could benefit post-surgical wound care in animals. Compositions comprising antibiotics and/or antifungals may be used to treat ear infections (e.g. otitis media, otitis externa) in animals such as dogs and/or cats. Compositions and formulations of the invention may provide relief for domesticated companion animals suffering from hot spots (acute moist dermatitis) through its soothing and anti-inflammatory properties. Compositions comprising inflammatory drugs may be used to treat flea allergy dermatitis, thereby alleviating itching and inflammation. The deep penetrating capabilities of the technology has applications in hoof care for horses, treating infections like thrush and/or white line disease. Compositions comprising NSAIDs or other (e.g. natural) anti-inflammatory agents could be used to manage chronic joint pain in older domesticated companion animals. Compositions comprising UV filtering agents could be used to protect animals from the sun, for example sunburn, such as white-faced cattle, horses, or dogs. Preferred embodiments In one preferred embodiment: - The eutectic mixture comprises a hydrogen bond donor and a hydrogen bond acceptor; - The oil comprises a fatty acid, fatty alcohol, terpene and/or terpenoid; - The amount of water is 10 wt% or less; - The amount of volatile organic solvent is 10 wt% or less; - The volatile organic solvent is ethanol and/or acetate; and - The composition is pharmaceutically In one preferred embodiment: - The eutectic mixture comprises a hydrogen bond donor and a hydrogen bond acceptor; - The composition and/or the formulation comprises the eutectic mixture in an amount, by weight, of 1% or more (e.g. from 1 to 80%, such as from 8 to 50%); - The oil comprises a fatty acid, fatty alcohol, terpene and/or terpenoid; - The composition and/or the formulation comprises the oil in an amount, by weight, of 1% or more (e.g. from 1 to 95%, such as from 8 to 85%); - The amount of water is 1 wt% or less; - The amount of volatile organic solvent is 10 wt% or less; - The volatile organic solvent is ethanol and/or ethyl acetate; and - The composition is pharmaceutically acceptable. In one preferred embodiment: - The eutectic mixture comprises a hydrogen bond donor selected from the list consisting of: alcohols (such as phenol, menthol, thymol, chloroxylenol dodecanol, polyols (such as glycerol and sorbitol); sugars (such as fructose, glucose, sucrose, xylose) and diols (such as ethylene glycol, 1,2-propanediol, 1,4-butanediol, resorcinol)); amino acids (such as arginine, glycine, lysine, proline and serine); amines (such as dimethylurea, urea, thiourea); amides (such as acetamide, benzamide, niacinamide); nitrogen containing heterocyclic compounds (such as imidazole); and carboxylic acids (such as acetic acid, propionic acid, butyric acid, valeric acid, caprylic acid, oxalic acid, malic acid and benzoic acid ascetic acid, ascorbic acid, carbonic acid, citric acid, formic acid, glycolic acid, glutaric acid, lactic acid, maleic acid, malonic acid, salicylic acid); and comprises a hydrogen bond acceptor selected from the list consisting of: quaternary ammonium salt (such as tetramethylammonium chloride, tetraethylammonium chloride, tetrabutylammonium chloride, N,N-diethyl-2-hydroxy ethanamidium chloride, N-benzyl-2-hydroxy-N,N- dimethyl ethanamidium chloride, 2-acetyl-N,N,N-trimethyl ethanamidium chloride and choline salts (such as choline chloride and acetylcholine)); amines (such as dimethylurea, urea and thiourea); amides (such as lidocaine); polyols (such as glycerol and sorbitol); carboxylic acids (such as acetic acid, propionic acid, butyric acid, valeric acid, caprylic acid, oxalic acid, malic acid and benzoic acid ascetic acid, ascorbic acid, carbonic acid, citric acid, formic acid, glycolic acid, glutaric acid, lactic acid, maleic acid, malonic acid, salicylic acid); phosphonium salts (such as methyltriphenylphosphonium bromide); alcohols (such as menthol, thymol, and chloroxylenol); and betaine; - The oil comprises: terpinen-4-ol, γ-terpinene, 1,8-cineole, α-terpinene, α-terpineol, p-cymene, and/or α- pinene; 1,8-cineol, camphor, α-pinene, limonene, camphene, linalool, eugenol, eugenyl acetate, β- caryophyllene, α-humulene; oleic acid, linoleic acid, stearic acid, α-linolenic acid, palmitic acid, arachidic acid, eicosenoic acid, erucic acid, cis-11-eicosenol, cis-13-docosenol, and/or cis-15-tetracosenol; - The composition/formulation comprises a surfactant - The amount of water is 1 wt% or less; - The amount of volatile organic solvent is 10 wt% or less; - The volatile organic solvent is ethanol and/or acetate; - Any biologically active agent (for the composition) is an antimicrobial agent and/or an anti-hair loss agent; and - The composition is pharmaceutically acceptable. In one preferred embodiment: - The eutectic mixture comprises a hydrogen bond donor that is glycolic acid, glutaric acid, acetic acid, glycerol and/or urea; and a hydrogen bond acceptor that is a quaternary ammonium salt (such as a choline salt), glutaric acid and/or an amine (such as urea). - The oil comprises: terpinen-4-ol, γ-terpinene, 1,8-cineole, α-terpinene, α-terpineol, p-cymene, and/or α- pinene; 1,8-cineol, camphor, α-pinene, limonene, camphene, linalool, eugenol, eugenyl acetate, β- caryophyllene, α-humulene; oleic acid, linoleic acid, stearic acid, α-linolenic acid, palmitic acid, arachidic acid, eicosenoic acid, erucic acid, cis-11-eicosenol, cis-13-docosenol, and/or cis-15-tetracosenol; - The composition/formulation comprises a surfactant - The amount of water is 1 wt% or less; - The amount of volatile organic solvent is 5 wt% or less; - The volatile organic solvent is acetone, ethyl acetate and/or ethanol; - Any biologically active agent (for the composition) is an antimicrobial agent, a psoriasis treatment agent, a diabetic foot ulcer treatment agent, a burn wound treatment agent, a dermatitis treatment agent, a wart treatment agent, a varicose vein treatment agent, an osteoarthritis treatment agent, a haemorrhoid treatment agent, a dermatitis treatment agent, an anti-cancer agent, an anti-inflammatory agent, a cosmetic active ingredient, an anti-cancer agent, an acne treatment agent and/or an anti-hair loss agent; and - The composition is pharmaceutically acceptable. In one preferred embodiment: - The eutectic mixture a hydrogen bond donor that is glycolic acid, glutaric acid, acetic acid, glycerol and/or urea; and a hydrogen bond acceptor that is a quaternary ammonium salt (such as a choline salt), glutaric acid and/or an amine (such as urea). - The composition and/or the formulation may comprise the eutectic mixture in an amount, by weight, of 1% or more (e.g. from 1 to 80%, such as from 8 to 50%); - The oil comprises: terpinen-4-ol, γ-terpinene, 1,8-cineole, α-terpinene, α-terpineol, p-cymene, and/or α- pinene; 1,8-cineol, camphor, α-pinene, limonene, camphene, linalool, eugenol, eugenyl acetate, β- caryophyllene, α-humulene; oleic acid, linoleic acid, stearic acid, α-linolenic acid, palmitic acid, arachidic acid, eicosenoic acid, erucic acid, cis-11-eicosenol, cis-13-docosenol, and/or cis-15-tetracosenol; - The composition and/or the formulation comprises the oil in an amount, by weight, of 1% or more (e.g. from 1 to 95%, such as from 8 to 85%); - The composition/formulation comprises a surfactant - The amount of the surfactant is 0.1% or more (e.g. from 0.1 to 80%, such as from 1 to 20%) by weight; - The amount of water is 0.1 wt% or less; - The amount of volatile organic solvent is 5 wt% or less; - The volatile organic solvent is an alcohol (for methanol, ethanol, propanol, butanol) and/or a polar aprotic solvent (such as ethyl acetate, acetone, acetonitrile); - Any biologically active agent (for the composition) is an antifungal agent (e.g. azoles (including imidazoles and triazoles) such as miconazole, ketoconazole, clotrimazole, econazole, bifonazole, butoconazole, fenticonazole, isoconazole, oxiconazole, sertaconazole, sulconazole, tioconazole, itraconazole, fluconazole, voriconzole, terconazole, isavuconazole, ravuconazole, and posaconazole; polyenes such as natamycin, rimocidin, filipin, nystatin, candicidin, nystatin, candicidin, and amphoteracin B; thiazoles such as abafungin; echinocandins; allylamines such as terbinafine, amorolfine, naftifine, and terbinafine; thiocarbamates such as tolnaftate; phenolic compounds such as haloprogin; pyridones such as ciclopirox olamine; and miscellaneous antifungal agents such as undecylenic acid), an antibacterial agent (e.g. a penicillin (such as phenoxymethylpenicillin, flucloxacillin, amoxycillin), a macrolide (such as clarithromycin, azithromycin, erythromycin), a cephalosporin (such as cefaclor, cefadroxil and cefalexin), and/or a tetracycline (such as tetracycline, doxycycline and lymecycline)), a psoriasis treatment agent (e.g. vitamin D or an analogue thereof (e.g. alfacalcidol, calcipotriol (calcipotriene), doxercalciferol, falecalcitriol, paricalcitol, tacalcitol), a corticosteroid, calcineurin inhibitors such as tacrolimus and pimecrolimus, coal tar, dithranol), an anti-hair loss agent (e.g. finasteride, minoxidil, and/or ketoconazole), an ulcer treatment agent (e.g. growth factors, silver nanoparticles), a burn wound treatment agent (e.g. aloe vera extract, honey, silver sulfinamide, mafenide, and/or chlorhexidine), a dermatitis treatment agent (e.g. clotrimazole, econazole, miconazole, terbinafine, fluconazole, ketoconazole, nystatin and/or amphotericin), a wart treatment agent (e.g. keratolytic agents such as salicylic acid, urea, and/or alpha-hydroxy acids), a varicose vein treatment agent (e.g. venotonic agents such as escin and/or a flavonoid), an osteoarthritis treatment agent (e.g. a NSAID, such as diclofenac, ibuprofen, naproxen, celecoxib, and/or rofecoxib), a haemorrhoid treatment agent (e.g. anti-inflammatory and/or analgesic drug such as ibuprofen, naproxen, diclofenac, celecoxib, mefenamic acid, etoricoxib, indomethacin, and/or aspirin), a dermatitis treatment agent (e.g. emollients, topical corticosteroids, cyclosporine, calcineurin inhibitors (such as tacrolimus and pimecrolimus), crisaborole, ruxolitinib, and/or hydrating agents (such as hyaluronic acid)), an anti-cancer agent (e.g. chemotherapeutic drugs and/or immune response modifier), an anti-inflammatory agent (e.g. ibuprofen, naproxen, diclofenac, celecoxib, mefenamic acid, etoricoxib, indomethacin, and/or aspirin), a cosmetic active ingredient (e.g. an alpha hydroxy acid, benzoyl peroxide, a beta hydroxy acid, ceramides, hyaluronic acid, hydroquinone, vitamin A or an analogue thereof, vitamin C or an analogue thereof), and/or an acne treatment agent (e.g. salicylic acid or derivatives thereof, benzoyl peroxide or derivatives thereof, retinoids such as retinoic acids or tretinoin, azelaic acid and derivatives thereof); and - The composition is pharmaceutically acceptable. In one preferred embodiment: - The eutectic mixture is selected from the list consisting of: Phenol/Menthol; Phenol/Choline chloride; Phenol/Choline chloride/Urea Choline chloride/Urea; Betaine hydrochloride; Resorcinol/Choline chloride; BHT/Choline chloride; Chloroxylenol/Choline chloride/Menthol; Choline chloride/Citric acid monohydrate; Choline chloride/Arginine/Urea; Choline chloride/Niacinamide/Urea; Camphor/Menthol; Camphor/Menthol/Lauryl alcohol; mono laurate/Menthol; Terbinafine hydrochloride/lidocaine; Urea/Glycolic acid; Choline chloride/Glutaric acid; Choline chloride/Acetic acid; Choline chloride/Glycerol; and Glutaric acid/Glycerol; - The oil is tea tree oil, eucalyptus oil, citronella, lavender oil, cinnamon oil, peppermint oil, clove oil, thyme oil, black pepper oil, geranium oil, coconut oil, olive oil, shea butter, jojoba oil, argan oil, baobab oil, castor oil, coconut oil, hemp seed oil and/or sesame oil; - The composition/formulation comprises a surfactant that is a non-ionic surfactant - The amount of water is 0.001 wt% or less; - The amount of volatile organic solvent is 1 wt% or less; - The volatile organic solvent is an alcohol (for example methanol, ethanol, propanol, butanol) and/or a polar aprotic solvent (such as ethyl acetate, acetone, acetonitrile); - Any biologically active agent (for the composition) is an antifungal agent (e.g. azoles such as miconazole, ketoconazole, clotrimazole, econazole, bifonazole, butoconazole, fenticonazole, isoconazole, oxiconazole, sertaconazole, sulconazole, tioconazole, itraconazole, fluconazole, voriconzole, terconazole, isavuconazole, ravuconazole, and posaconazole; polyenes such as natamycin, rimocidin, filipin, nystatin, candicidin, nystatin, candicidin, and amphoteracin B; thiazoles such as abafungin; echinocandins; allylamines such as terbinafine, amorolfine, naftifine, and terbinafine; thiocarbamates such as tolnaftate; phenolic compounds such as haloprogin; pyridones such as ciclopirox olamine; and miscellaneous antifungal agents such as undecylenic acid), an antibacterial agent (e.g. a penicillin (such as phenoxymethylpenicillin, flucloxacillin, amoxycillin), a macrolide (such as clarithromycin, azithromycin, erythromycin), a cephalosporin (such as cefaclor, cefadroxil and cefalexin), and/or a tetracycline (such as tetracycline, doxycycline and lymecycline)), and/or an anti-hair loss agent (e.g. finasteride, minoxidil, and/or ketoconazole), an ulcer treatment agent (e.g. growth factors, silver nanoparticles); and - The composition is pharmaceutically acceptable. In one preferred embodiment: The eutectic mixture is choline chloride and urea; urea and glycolic acid; urea and glycerol; choline chloride and glutaric acid; choline chloride and acetic acid; choline chloride and glycerol; and/or glutaric acid and glycerol; - The oil is tea tree oil, eucalyptus oil, citronella, lavender oil, cinnamon oil, peppermint oil, clove oil, thyme oil, black pepper oil, geranium oil, coconut oil, olive oil, shea butter, jojoba oil, argan oil, baobab oil, castor oil, coconut oil, hemp seed oil and/or sesame oil; - The composition/formulation comprises a surfactant that is a non-ionic surfactant - The amount of water is 0.001 wt% or less; - The amount of volatile organic solvent is 1 wt% or less; - The volatile organic solvent is a nonpolar solvent, such as a nonpolar hydrocarbon solvent (such as pentane, cyclopentane, hexane, cyclohexane, heptane, benzene and toluene); a nonpolar ether solvent (such as diethyl ether, 1,4-dioxane, methyl tert-butyl ether, glyme, and tetrahydrofuran); a polar aprotic solvent (such as ethyl acetate, acetone and acetonitrile); a polar protic solvent (such as alcohols, for example methanol, ethanol, propanol (e.g. isopropanol, n- , butanol (e.g. tert-butanol)), and/or a carboxylic acid (such as acetic acid and formic acid); - Any biologically active agent (for the composition) is clotrimazole, terbinafine, flucloxacillin finasteride and/or minoxidil; and - The composition is pharmaceutically acceptable. In one preferred embodiment: The eutectic mixture is choline chloride and urea; urea and glycolic acid; urea and glycerol; choline chloride and glutaric acid; choline chloride and acetic acid; choline chloride and glycerol; and/or glutaric acid and glycerol; - The composition and/or the formulation may comprise the eutectic mixture in an amount, by weight, of 1% or more (e.g. from 1 to 80%, such as from 8 to 50%); - The oil is tea tree oil, eucalyptus oil, citronella, lavender oil, cinnamon oil, peppermint oil, clove oil, thyme oil, black pepper oil, geranium oil, coconut oil, olive oil, shea butter, jojoba oil, argan oil, baobab oil, castor oil, coconut oil, hemp seed oil and/or sesame oil; - The composition and/or the formulation comprises the oil in an amount, by weight, of 1% or more (e.g. from 1 to 95%, such as from 8 to 85%); - The composition/formulation comprises a surfactant that is a non-ionic surfactant - The amount of the surfactant is 0.1% or more (e.g. from 0.1 to 80%, such as from 1 to 20%) by weight; - The amount of water is 0.001 wt% or less; - The amount of volatile organic solvent is 1 wt% or less; - The volatile organic solvent is a nonpolar solvent, such as a nonpolar hydrocarbon solvent (such as pentane, cyclopentane, hexane, cyclohexane, heptane, benzene and toluene); a nonpolar ether solvent (such as diethyl ether, 1,4-dioxane, methyl tert-butyl ether, glyme, and tetrahydrofuran); a polar aprotic solvent (such as ethyl acetate, acetone and acetonitrile); a polar protic solvent (such as alcohols, for example methanol, ethanol, propanol (e.g. isopropanol, n-propanol), butanol (e.g. tert-butanol)), and/or a carboxylic acid (such as acetic acid and formic acid); - Any biologically active agent (for the composition) is clotrimazole, terbinafine, flucloxacillin finasteride and/or minoxidil; and - The composition is pharmaceutically acceptable. In one preferred embodiment the composition and/or formulation comprises a microemulsion and: - the surfactant is a polyoxyethylene ether (e.g. Brij 97); - the surfactant is included in an amount of from 21 to 39 wt% (e.g. from 22 to 38 wt%, such as from 25 to 35 wt%, or from 28 to 32 wt%); - The eutectic mixture comprises urea and/or glycolic acid; - The eutectic mixture is included in an amount of from 11 to 29 wt% (e.g. from 12 to 28 wt%, or from 15 to 25 wt%, such as from 18 to 22 wt%); - the oil comprises terpenes and/or terpenoids tea tree oil, eucalyptus oil, citronella, lavender oil, cinnamon oil, peppermint oil, clove oil, thyme black pepper oil, geranium oil, and/or coconut oil – preferably clove oil); and - the oil is included in an amount of from 41 to 59 wt% (such as from 42 to 58 wt%, or from 45 to 55 wt%, e.g. from 48 to 52 wt%). The formulation may comprise Urea/Glycolic Acid or Choline Chloride/Urea as the DES, jojoba oil as the oil. Such a formulation may be combined with Corticosteroids and/or Vitamin D analogues. Such compositions may find particular benefits in the treatment of psoriasis, due to the benefits provided in terms of localised delivery reducing systemic side effects. Current treatments for psoriasis can have problematic systemic side effects and skin irritation. The DES/oil provides the benefits of enhanced skin barrier penetration and reduced inflammation. The formulation may comprise Choline Chloride/Glycerol or Glycerol/Sodium Acetate as the DES, and Almond Oil as the oil. Such a formulation may be combined with Growth factors and/or Silver nanoparticles. Such compositions may find particular benefits in the treatment of diabetic foot ulcers. Conventional compositions for the treatment of diabetic foot ulcers provide a risk of infection, and slow healing. This composition may provide enhanced healing due to increased stability of the active. The DES/oil provides the benefits of improved stability of the active and enhanced wound healing. The formulation may comprise Choline Chloride/Urea or Betaine/Glycerol as the DES, and Tea Tree Oil as the oil. Such a formulation may be combined with Benzoyl peroxide and/or Salicylic acid. Such compositions may find particular benefits in the treatment of Acne Vulgaris. Conventional compositions for the treatment of Acne Vulgaris can provide skin dryness, irritation and thus increased resistance. This composition may provide targeted delivery and reduced irritation. The DES/oil provides the benefits of controlled release, and decreased skin dryness. The formulation may comprise Glycerol/Urea or Lactic Acid/Choline Chloride as the DES, and Coconut Oil as the oil. Such a formulation may be combined with a corticosteroid and/or a hydrating agent. Such compositions may find particular benefits in the treatment of Atopic Dermatitis (Eczema). Conventional compositions for the treatment of Atopic Dermatitis (Eczema) use systemic absorption, which carries risks of side effects, and skin thinning. This composition may provide improved moisturization and minimized systemic absorption. The DES/oil provides the benefits of sustained hydration, reduced skin irritation and reduced skin thinning. The formulation may comprise Glycolic Acid/Urea or Menthol/Urea as the DES, and Aloe Vera Oil as the oil. Such a formulation may be combined with Silver sulfadiazine and/or Aloe vera. Such compositions may find particular benefits in the treatment of wounds, such as burn wounds. Conventional compositions for the treatment of wounds, such as burn wounds carry a risk of infection, and provide inadequate pain relief. This composition may provide Sustained release and/or Enhanced penetration. The DES/oil can provide the benefits of Optimized healing environment and/or Enhanced drug stability. The formulation may comprise Glycerol/Choline Chloride or Citric Acid/Sucrose as the DES, and Eucalyptus Oil as the oil. Such a formulation may be combined with Salicylic acid and/or Keratolytic agents. Such compositions may find particular benefits in the treatment of Plantar Warts. Conventional compositions for the treatment of Plantar Warts can provide Irritation and Pain during treatment. This composition may provide Efficient drug delivery and/or Enhanced penetration. The DES/oil may provide the benefits of Deep tissue penetration and Efficient keratolysis. The formulation may comprise Choline Chloride/Glycerol as the DES, and Witch Hazel Oil as the oil. Such a formulation may be combined with Anti-inflammatory and/or Analgesic compounds. Such compositions may find particular benefits in the treatment of haemorrhoids. Conventional compositions for the treatment of haemorrhoids can provide systemic side effects and only temporary relief. This composition may provide localized pain relief and reduced systemic side effects. The DES/oil provides the benefits of enhanced local absorption, and minimized systemic impact. The formulation may comprise Choline Chloride/Glycerol or Menthol/Urea as the DES, and Olive Oil as the oil. Such a formulation may be combined with NSAIDs and/or Analgesics. Such compositions may find particular benefits in the treatment of Osteoarthritis. Conventional compositions for the treatment of Osteoarthritis provide Gastrointestinal side effects and limited efficacy. This composition may provide targeted relief and reduced systemic side effects. The DES/oil may provide the benefits of improved joint lubrication and enhanced drug delivery. The formulation may comprise Urea/Glycolic Acid or Lactic Acid/Choline Chloride as the DES, and Sunflower Oil as the oil. Such a formulation may be combined with Antifungal agents and/or Ketoconazole. Such compositions may find particular benefits in the treatment of Seborrheic Dermatitis. Conventional compositions for the treatment of Seborrheic Dermatitis are met with resistance to antifungal agents and provide skin irritation. This composition may provide enhanced stability and targeted treatment. The DES/oil may provide the benefits of increased antifungal delivery/effectiveness, and decreased irritation. The formulation may comprise Choline Chloride/Glycerol or Betaine/Glycerol as the DES, and Witch Hazel Oil as the oil. Such a formulation may be combined with venotonics and/or anti-inflammatory drugs. Such compositions may find particular benefits in the treatment of Varicose Veins. Conventional compositions for the treatment of Varicose Veins can provide Limited efficacy and Skin irritation. This composition may provide Improved efficacy and Enhanced patient/user comfort. The DES/oil can provide the benefits of enhanced vein wall penetration and improved symptom relief. The formulation may comprise Glycolic Acid/Choline Chloride or Citric Acid/Sucrose, as the DES, and Rosehip Oil as the oil. Such a formulation may combined with chemotherapeutic agents and/or immune response modifiers. Such compositions may find particular benefits in the treatment of carcinoma (e.g. skin cancer). Conventional compositions for the treatment of carcinoma (e.g. skin cancer) can provide systemic toxicity and adverse reactions. This composition may provide targeted therapy, minimized systemic toxicity. The DES/oil provides the benefits of targeted delivery to cancer cells, reduced healthy tissue impact. Examples General procedure for preparation of deep eutectic solvents (DES) DESs were synthesized through a process involving different molar ratios (2:1, 1.5:1, 1:1, 1:1.5, and 1:2) of urea to other components (glycolic acid, glycerol, or choline chloride). The mixture of urea and other component was placed in a glass jar, which was then submerged in a water bath. The bath was heated to 60°C, and the mixture was stirred until it formed a homogenous clear liquid. This eutectic liquid was then stored at room temperature in a sealed jar. For concise identification, the DES components were labelled as follows: Glu: glutaric acid; U: urea; AA: acetic acid; GA: glycolic acid; G: glycerol; and CC: choline chloride. A specific DES was prepared with a 1:1 molar ratio of urea to glycolic acid, a 1:2 molar ratio of urea to glycerol, and a 2:1 ratio of urea to choline chloride. All DESs were provided as clear (transparent), colourless liquids. Using the aforementioned approach, various DES categories were formulated using a hydrogen acceptor compound chlorine chloride and various hydrogen donor compounds such as glutaric acid, acetic acid, and glycerol, as well as the creation of a DES between glutaric acid as the hydrogen acceptor compound and glycerol as the hydrogen donor compound under identical conditions. Glutaric acid is able to act either as a hydrogen acceptor or as a hydrogen donor compound. Characterization of urea/glycolic acid DES The molecular composition of the synthesized DES (U/GA) was analysed using FTIR. The FTIR spectrum of U/GA revealed the distinct absorption peaks characteristic of urea and glycolic acid, but these peaks were slightly shifted towards shorter wavelengths. This shift indicated the formation of hydrogen bond interactions between urea and glycolic acid, confirming the successful creation of a eutectic liquid mixture from these two components. Preparation of formulations of the invention Emulsions were prepared by combining with clove oil and a surfactant (e.g. Brij 97, hydrophilic–lipophilic balance=12). Different DESs were examined, such as U/GA, CC/Glu, CC/AA, CC/G, and Glu/G. Various amounts of the components were used, as detailed in Table 1 (below). Table 1. The preparation of DES-based microemulsion mixture using different weight ratios between components DES (wt.%) Brij 97 (Surfactant) Oil (clove oil) (wt.%) (wt.%) 10% 10% 80% 10% 20% 70% 10% 30% 60% 20% 10% 70% 20% 20% 60% 20% 30% 50% 30% 10% 60% 30% 20% 50% 30% 30% 40% 40% 10% 50% 40% 20% 40% 40% 30% 30% Notably, successful microemulsion mixtures were achieved with Brij 97. The preparation process with Brij 97 involved mixing a specific weight of DES with Brij 97, while stirring continuously at 50°C until a clear, homogenous liquid was formed. The DES/Brij 97 blend was gradually introduced into the clove oil, dropwise, maintaining continuous stirring at 50°C to provide a microemulsion. The microemulsion was then maintained at this temperature for 10 minutes. Following this, the temperature control was turned off, and the mixture was left to stir overnight. All formulations were provided as clear (transparent) liquids, suggesting that emulsions were formed. It was determined that 20wt% DES (U/GA) / 30wt% surfactant (Brij 97) / 50wt% oil (clove oil) resulted in a one-phase emulsion (microemulsion). Other formulations exhibited two phases (emulsions). Formulations of the invention were prepared comprising 20wt% DES (urea/glycolic acid) / 30wt% surfactant (Brij 97) / 50wt% oil. The oil was one of various natural essential oils: clove oil, rosemary oil, tea tree oil, and/or olive oil. This shows that one-phase emulsions (microemulsions) can be successfully prepared with a variety of different oils. Microemulsions using the ratio of 20wt% DES acid) / 30wt% surfactant / 50wt% oil (clove oil) were prepared utilizing different including Brij 97 (HLB 12), Span 20 (HLB 8.6), Span 80 (HLB 4.3), and Pluronic L-61 (HLB 3). Therefore, that one-phase emulsions (microemulsions) can be successfully prepared with a variety of different surfactants, the surfactants had different HLB values. Characterization of urea/glycolic acid / Brij 97 / clove oil formulation The U/GA /Brij 97/clove oil microemulsion prepared as described above was selected for further characterization. The molecular composition of the microemulsion mixture was analysed by FTIR, and compared with the individual components Brij 97, clove oil, and DES. The FTIR spectrum of the emulsion displayed all the characteristic absorption peaks of these components - clove oil, Brij 97, and the DES - with a slight shift in the wavenumbers. This shift suggests the successful formation of the emulsion solution, likely due to hydrogen-bonding interactions among the components. Topical compositions for treating fungal nail infections (onychomycosis) Preparation of antifungal drug-loaded emulsion mixture Clotrimazole and terbinafine hydrochloride are two representative antifungal agents that are frequently used in topical treatments for nail infections caused by onychomycosis. Other similar antifungal agents include griseofulvin. Clotrimazole and terbinafine hydrochloride (each individually and combine), as well as their combined formulations, were integrated into the microemulsion of 20wt% DES (urea/glycolic acid) / 30wt% surfactant (Brij 97) / 50wt% oil (clove oil). The drugs (1.0%, 2.0%, 3.0%, 4.0%, and 5.0% w/w) were blended into 1g of the emulsion, followed by continuous stirring at room temperature overnight. Figure 2 of the accompanying drawings shows a schematic representation of the experiment performed, with photographs of the starting emulsion and the resulting compositions. The experiment yielded clear, homogenous one-phase emulsions for all drug concentrations. All compositions obtained were stable microemulsions. Characterisation of compositions Analysis by FTIR was performed on pure clotrimazole, the starting emulsion (20wt% DES (urea/glycolic acid) / 30wt% surfactant (Brij 97) / 50wt% oil (clove oil)), and the emulsion containing clotrimazole. The FTIR spectrum of the clotrimazole-infused emulsion mixture displayed characteristic peaks of both clotrimazole and the emulsion, but a slight shift in the wavenumbers. These shifts indicate a likely compatibility between clotrimazole and the microemulsion within the drug-emulsion formulation. The particle size of both the starting microemulsion and the clotrimazole-loaded microemulsion was determined using dynamic light scattering (DLS). Each sample was diluted in a 1:200 ratio with ultrapure water and then passed through a 0.45µm syringe filter prior to analysis with a Zetasizer Nano-ZS (Malvern, UK). All measurements were conducted with a refractive index set at 1.59 and an absorbance level of 0.01. Each sample underwent three separate measurements at 25°C, and the average values along with the standard deviation were recorded. The DLS results revealed that the particle size of the emulsion without the drug was 42.23 nm, with a polydispersity index (PDI) of 0.192. In contrast, the clotrimazole-loaded emulsion exhibited slightly larger dimensions (98.14 nm) and a higher PDI (0.250). This suggests that both the microemulsion and the drug-loaded microemulsion were successfully prepared within the nanoscale range. This size range and the nature of these oil-based mixtures suggests that microemulsions are formed as opposed to traditional emulsions. The difference between an emulsion and microemulsion is stability: emulsions are kinetically stable and will phase separate with time, while microemulsions are a type of emulsion that are also thermodynamically stable. Formulations prepared are clear (transparent), which confirmed that those mixtures were indeed microemulsions. Storage stability study Samples of the base microemulsion formulation (20wt% DES (urea/glycolic acid) / 30wt% surfactant (Brij 97) / 50wt% oil (clove oil)) and the three drug-microemulsion compositions (i.e. loaded with clotrimazole, or terbinafine, or clotrimazole and terbinafine) were stored at room temperature for a duration of 30 days to observe any changes. Figure 3 of the accompanying drawings shows photographs of the samples at 0, 14 and 30 days. After the 30-day storage period, there were no observable alterations in colour or clarity, suggesting that there were no signs of drug precipitation, in the formulation or any of the compositions. This confirms the stability of the formulations and compositions of the invention. In vitro permeation study To evaluate the penetration capability of the clotrimazole-loaded microemulsion, serving as a skin model, a Franz-diffusion cell with a cellulose membrane was utilized, with the drug concentration analysed via High-Performance Liquid Chromatography (HPLC). In this setup, the drug's diffusion was monitored through a dialysis cellulose membrane with a molecular weight cutoff of 12-14 kDa. Prior to the experiment, a 30mm × 30mm segment of the dialysis membrane was immersed in distilled water overnight. A Franz-diffusion cell with a 22 ml receptor compartment was used for the study. This pre-soaked membrane was positioned between the donor and receptor chambers. The receptor chamber was filled with a 30:70% v/v mixture of ethanol and phosphate buffer saline (pH 7), which was filtered through a 0.22µm syringe filter and maintained at 32°C in a water bath with stirring. Around 0.5 ml of the clotrimazole-loaded microemulsion was applied to the cellulose membrane in the donor chamber. At predetermined time intervals of 2, 3, 4, 24, and 48 hours, 1mL aliquots were extracted and replaced with an equal volume of fresh medium. These aliquots were subjected to HPLC analysis. The concentration of clotrimazole permeated from the clotrimazole-loaded microemulsion within the Franz-diffusion cell was quantified using HPLC. The chromatographic analysis was conducted on a C18 column (Avantor® ACE®, 75 x 4.6 mm) with a flow rate set at 1 mL/min, and the injection volume was fixed at 20 µL. The mobile phase comprised a 50:50 (v/v) mixture of HPLC-grade water and acetonitrile. UV detection was performed at 260 nm, and the calibration curve demonstrated a linear response (R² = 0.9989) over a concentration range of 10–200 µg/mL, fitting the linear equation A = 1.46*X + 1.17. Clotrimazole eluted at a retention time of 2.2 minutes, which was distinct from the retention time of the microemulsion at 2.67 minutes. The chromatogram of the clotrimazole-infused microemulsion revealed both peaks, confirming the presence of the microemulsion. The results of the HPLC analysis offer crucial insights into the drug release kinetics, playing an important role in determining the effectiveness and suitability of the microemulsion compositions for topical use. The levels of clotrimazole that permeated from the clotrimazole-loaded microemulsion through the membrane in the aliquots taken at 2, 3, 4, 24, and 48 hours are detailed in Table 2 (below). Table 2. The concentration of permeated clotrimazole from Franz-diffusion cell Time of Area under the Concentration of Clotrimazole (ppm) permeated Clotrimazole peak drug (h) (mAU*min) 2 29 19.1 ppm = 19.1 µg/mL 3 35.5 23.5 ppm= 23.5 µg/mL 4 66.3 44.6 ppm= 44.6 µg/mL 24 485.4 331.7 ppm= 331.7µg/mL=0.33 mg/mL 48 780.2 533.6 ppm= 533.6µg/mL=0.53 mg/mL The results indicate a consistent pattern of gradual release and diffusion of clotrimazole from the microemulsion over time, culminating in a concentration of 0.53 mg/mL after 48 hours. Despite the stability of the compositions, the active compound contained within the composition can be successfully released and penetrate through membranes. The results therefore highlight the benefits that can be attained from using compositions of the invention as a topical treatment. Nail Penetration Studies The penetration of clotrimazole drug into healthy human nails was investigated using two distinct methods: an immersion method and a drop method. Freshly cut nail clippings were collected from podiatrist in Reading, UK. Human nail clippings were collected from volunteers following ethics approval (43/2023) from Reading university. Immersion method study Healthy human nails were submerged in a drug-loaded microemulsion for varying time intervals (3h, 24h, 48h, and 72h). Following immersion, excess microemulsion was removed from the nail surface using tissue paper, and then the nails were dipped in ethanol for 3 seconds to eliminate any residual solution on its surface. Subsequently, all nails containing the penetrated drug were soaked in pure 0.5mL HPLC ethanol overnight, and the concentration of the extracted drug was determined using HPLC. Drop method studies A drop of drug-loaded microemulsion was applied onto healthy human nails. The nails were then covered with glass vials and left for specified time intervals of 3h, 24h, 48h, and 72h. After each time interval, excess microemulsion was wiped off from the nail surface using tissue paper, followed by a brief immersion of the nails in ethanol for 3 seconds to remove any remaining solution. Subsequently, all nails containing the permeated drug were immersed in pure 0.5mL HPLC ethanol overnight, and the concentration of the extracted drug was determined using HPLC analysis. The impact of adding ethanol to the prepared loaded microemulsion using the drop method was also examined. 20 wt% ethanol was incorporated the prepared drug-loaded microemulsion, and the penetration of the drug into human nails using the drop method, following the same procedure as described above. Results of Penetration Studies Table 3 (below) shows the results of the immersion method study for the composition of the invention. Table 3. The concentration of permeated clotrimazole from the penetration study using the immersion method Time of Area under the Concentration of Clotrimazole (ppm) permeated Clotrimazole peak drug (h) (mAU*min) 3 239.2 163.03 ppm = 163.03 µg/mL 24 581.1 397.21 ppm= 397.21 µg/mL 48 676.1 462.28 ppm= 462.28 µg/mL 72 745.9 510.08 ppm= 510.08µg/mL=0.33 mg/mL Table 4 (below) shows the results of the drop method study for the composition of the invention. Table 4. The concentration of permeated clotrimazole from the penetration study using the drop method Time of Area under the Concentration of Clotrimazole (ppm) permeated Clotrimazole peak drug (h) (mAU*min) 3 202.1 137.62 ppm = 137.62 µg/mL 24 318.6 217.41 ppm= 217.41 µg/mL 48 497.7 340.08 ppm= 340.08 µg/mL 72 672.5 459.8 ppm= 459.8µg/mL=0.33 mg/mL In both above methods, the data indicated that as the time interval increased, there was a corresponding rise in the penetration of the drug. A higher amount of clotrimazole was absorbed by the nails in the immersion study, likely due to the greater amount of clotrimazole that the nails were exposed to. Table 5 (below) shows the results of the drop method study for the composition comprising ethanol. Table 5. The concentration of permeated clotrimazole from the penetration study after adding ethanol to the prepared drug-loaded microemulsion using the drop method Time of Area under the Concentration of Clotrimazole (ppm) permeated Clotrimazole peak drug (h) (mAU*min) 3 20.3 13.10 ppm = 13.10 µg/mL 24 104.6 70.84 ppm= 70.84 µg/mL 48 303.6 207.14 ppm= 207.14 µg/mL 72 443.2 302.76 ppm= 302.76 µg/mL=0.33 mg/mL The results the composition of the invention significant increase in the amount of clotrimazole that penetrated into the nails compared to the ethanol-containing composition. Over relatively short timeframes the increase was greatest, being over 10 times higher than the composition containing ethanol. This effect cannot be explained simply by the concentration of the composition being affected by the ethanol, since the amount of ethanol in the comparative composition was only 20 wt% but the difference in effect was much higher than this. Figure 4 of the accompanying drawings shows photographs of nail samples obtained following from the drop method studies. Figure 4A shows a nail treated with the comparative composition containing ethanol. Figure 4B shows a nail treated with the composition of the invention. The nail treated with the comparative composition, shown by Figure 4A, appears to have dried; whereas the composition remains visibly present on the nail treated with the composition of the invention, as shown by Figure 4B. The volatility of the ethanol may have decreased the stability of the composition and/or caused the drug to precipitate on the nail surface, thereby forming a barrier for further absorption of the drug into the nail. Antibacterial compositions The stability of the antibiotic flucloxacillin (as a model antibiotic drug) was determined in water and in urea/glycolic acid deep eutectic solvent (DES). The antibiotic was dissolved in the DES as a means to create a new platform for the formulation of antibacterial creams. Various concentrations of flucloxacillin (1, 2, 3, 4, and 5% w/v) were each tested in water and in the DES, at a temperature of 20°C. Flucloxacillin was fully soluble in water and in the DES. Characterization of flucloxacillin composition The molecular composition of the flucloxacillin in DES was analysed using FTIR, and compared with the individual components of flucloxacillin, and the DES. The FTIR spectrum of the flucloxacillin in DES displayed overlapped all the characteristic absorption peaks of the flucloxacillin with the DES absorption peak with a slight shift in the wavenumbers, confirming the potential compatibility between flucloxacillin and the DES. Storage stability study Samples of all above concentrations were stored for a period of 10 days to observe any changes. During this time, the formation of precipitate in water-based drug samples was noted. The amount of precipitate increased visually with the concentration of flucloxacillin in the water. The amount of precipitation increased as time progressed. This indicates that the antibiotic degraded in water. In contrast, the flucloxacillin in DES showed no changes in colour, clarity or any other sign of drug precipitation in any concentration. This highlights the enhanced stability of the drug in compositions of the invention, which can be successful with a trace of or no water. Preparation of cream based on flucloxacillin composition An antibacterial cream containing flucloxacillin was prepared in the following manner. The oil phase, comprising 20wt% shea butter, 8wt% jojoba oil, and 10wt% emulsifying wax (cetearyl alcohol), was combined in a heat-resistant vessel and heated to 70°C. In parallel, the polar phase containing 60wt% DES and 2wt% flucloxacillin was also heated to 70°C in a separate container for 2 minutes. The polar phase was incrementally blended into the oil phase under continuous stirring, leading to the formation of a smooth, homogenous emulsion. After the emulsion was mixed, it was cooled with occasional stirring over an hour. The final cream was then placed into a clean, sanitized container for storage. The resulting product had a smooth and thick consistency, akin to a cream. This demonstrates that the compositions of the invention can successfully be used to prepare creams that are not water-based, and that therefore avoid or reduce stability issues for water sensitive medicaments. Hair loss compositions It was desired to create an innovative and effective topical solution for treating pattern hair loss. The anti-hair loss medications finasteride and minoxidil were incorporated into a formulation of the invention. The solubility of various concentrations of these two drugs in the formulation of the invention (20wt% DES (urea/glycolic acid) / 30wt% surfactant (Brij 97) / 50wt% oil (clove oil)) was investigated. Different concentrations of each of finasteride and minoxidil (0.25, 0.5, 1.0, and 3.0% w/w) were dissolved in 1g of the emulsion mixture. All concentrations of the drugs were completely soluble in the formulation of the invention, providing transparent liquids that appeared to retain the microemulsion form. Drug combination-loaded microemulsion mixture The preparation of a combined anti-hair loss treatment, comprising both finasteride and minoxidil in the formulation of the invention (20wt% DES (urea/glycolic acid) / 30wt% surfactant (Brij 97) / 50wt% oil (clove oil)) was investigated. Two distinct combinations were formulated: one with 0.25wt% Finasteride and 3.0wt% Minoxidil, and another with 3.0wt% Finasteride and 0.25wt% Minoxidil, both in the formulation of the invention. It was noted that while both mixtures resulted in clear (transparent) and homogenous microemulsions, the mixture with a higher concentration of minoxidil exhibited a more yellow colour. This colouration aligns with the natural, faint yellow hue characteristic of minoxidil. FTIR was used to characterise the combined composition. The spectra showed the distinct absorption peaks of the pure drugs, the microemulsion without any drug, and the microemulsion mixture loaded with the drug combination. As a representative model, the microemulsion containing a 3.0% Finasteride and 0.25% Minoxidil combination was analysed. The FTIR spectrum of this drug-laden microemulsion exhibited the characteristic peaks of both the drugs and the emulsion, but with noticeable shifts across all wavenumbers. These shifts suggest compatibility between the two drugs and the formulation within the combined composition. Antifungal nail treatment Preparation of choline chloride/urea eutectic mixture 21.5 g of choline chloride (0.154 mol) and 18.5 g of urea (0.308 mol) were weighed and mixed in a glass vessel and heated on water bath which was maintained at to 100 °C. Initially, the mixture was agitated with a spatula, but as it became more fluid, stirring was conducted with a PTFE covered magnetic stirrer. Complete dissolution was observed after 15 minutes. Preparation of base emulsion 100 mg of clove oil were mixed with 1700 mg of the eutectic mixture described above and 200 mg of polyethoxylated sorbitan monooleate (Tween 80®) using a mechanical stirrer at 20 °C. An emulsion formed within a matter of minutes. The emulsion was assessed for stability every 24h, and appeared stable indefinitely. Preparation of griseofulvin formulation according to the invention. 500 mg of clove oil, 1300 mg of the eutectic composition described above, 100 mg of polyethoxylated sorbitan monooleate (Tween 80®) and 100 mg of griseofulvin (GF) were mixed using a mechanical stirrer at 20 °C. An opaque suspension was formed. The emulsion was assessed for stability every 24h, and appeared stable indefinitely. Assessment of permeability through bovine hooves Raman mapping In this study bovine hooves were used as model human nail according to the method of European Journal of Pharmaceutics and Biopharmaceutics 179 (2022) 194–205 (incorporated herein by reference). To assess permeability, Raman mapping was used as opposed to other methods used in the literature. The rationale for using Raman mapping is the ability to distinguish the drug from other components but more importantly is the simulation of real conditions that are used when the formulation was to be applied by the patient. The analytical benefit of this technique is that the drug can be differentiated from the hoof tissue. The sliced bovine hooves were immersed in the composition noted above for 24h and then removed and dried. Any residual powder was removed to ensure that the measured spectra reflect drug that penetrated through the tissue. Figure 1 of the accompanying drawings shows three Raman spectra. These spectra are overlayed and include untreated hoof sample, pure GF, and hoof samples following treatment with GF. The spectra revealed the presence of GF in the hoof samples.

Claims

CLAIMS 1. A composition comprising: a) an emulsion comprising: i) a eutectic mixture, and ii) an oil; and b) a biologically active agent.

2. The composition of claim 1, wherein the composition comprises less than 20wt% volatile organic solvent, or contains no volatile organic solvent.

3. The composition of claim 2, wherein the composition comprises 10wt% or less volatile organic solvent, or contains no volatile organic solvent.

4. The composition of claim 2 or claim 3, wherein the volatile organic solvent is ethanol and/or ethyl acetate.

5. The composition of any one of claim 4, wherein the volatile organic solvent is selected from the list consisting of: pentane, cyclopentane, hexane, cyclohexane, heptane, benzene, toluene, diethyl ether, 1,4-dioxane, methyl tert-butyl ether, glyme, tetrahydrofuran, ethyl acetate, acetone, acetonitrile, methanol, ethanol, propanol, butanol, acetic acid and formic acid.

6. The composition of any preceding claim, wherein the composition comprises water in an amount of 1 wt% or less.

7. The composition of any preceding claim, wherein the composition is pharmaceutically acceptable.

8. The composition of any preceding claim, wherein the composition is for topical administration.

9. The composition of any preceding claim, wherein the eutectic mixture comprises: (i) choline chloride and urea; (ii) urea and glycolic acid; (iii) urea and glycerol; (iv) choline chloride and glutaric acid; (v) choline chloride and acetic acid; (vi) choline chloride and glycerol; and/or (vii) glutaric acid and glycerol.

10. The composition of any preceding claim, wherein the oil is selected the list consisting of: tea tree oil, eucalyptus oil, citronella, lavender oil, oil, peppermint oil, clove oil, thyme oil, black pepper oil, geranium oil, coconut oil, rosemary oil, and olive oil.

11. The composition of claim 10, wherein the oil is selected from the list consisting of: clove oil, tea tree oil, rosemary oil and olive oil.

12. The composition of any preceding claim, further comprising a surfactant.

13. The composition of claim 12, wherein the surfactant is a nonionic surfactant.

14. The composition of claim 13, wherein the surfactant is a polyethoxylated sorbitan ester; a polyoxyethylene ether; and/or a block copolymer of ethylene oxide and propylene oxide.

15. The composition of any preceding claim, wherein composition is a microemulsion.

16. The composition of any preceding claim, wherein the biologically active agent is selected from the list consisting of: an antifungal agent; an antibiotic; an anti-hair loss agent; a psoriasis treatment agent; an ulcer treatment agent; an acne treatment agent; a dermatitis treatment agent; a burn wound treatment agent; a wart treatment agent; a haemorrhoid treatment agent; an osteoarthritis treatment agent; a dermatitis treatment agent; a varicose vein treatment agent; and an anti-cancer agent.

17. The composition of claim 16, wherein the biologically active agent is selected from the list consisting of: a corticosteroid, vitamin D or an analogue thereof, a growth factor, silver nano particles, benzoyl peroxide, salicylic acid, a hydrating agent, silver sulfadiazine, aloe vera, a keratolytic agent, an anti-inflammatory agent, an analgesic agent, flucloxacillin, an antifungal agent, ketoconazole, venotonics, a chemotherapeutic agent and an immune response modifier.

18. The composition of any preceding claim, wherein the composition is in the form of a cream, gel, lotion, spray, paste, balm, or wax.

19. A composition for use as a medicament, wherein the composition is of any preceding claim.

20. A composition for use in a method of treatment, prevention or amelioration of a condition or disease selected from the list consisting of: a microbial infection; pattern hair loss; psoriasis; foot ulcers; acne; dermatitis; wounds; warts; haemorrhoids; osteoarthritis; seborrheic dermatitis; varicose veins; and skin cancer, wherein the composition is as defined by any one of claims 1 to 18.

21. The composition for use of claim 20, wherein the condition or disease is a microbial infection that is a fungal infection, and the fungal caused by a fungus of a genus selected from the list consisting of: Candida, Neoscytalidum, Scopulariopsis, Trichophyton, and Aspergillus.

22. A formulation comprising an emulsion of: i) a eutectic mixture, and ii) an oil.

23. A method for preparing the formulation, the method comprising: i) forming a eutectic mixture of the at least one hydrogen acceptor and at least one hydrogen donor; and ii) emulsifying the eutectic mixture with oil.

24. A method of preparing a composition, the method comprising: i) obtaining a formulation comprising an emulsion of a eutectic mixture and an oil; and ii) adding a biologically active agent to the formulation.