The kit contains an oil-in-water emulsion and a stabilizer container for stabilizing the prostaglandin emulsion, along with a method for producing it.

Abstract

The invention relates to a kit (1) containing an oil-in-water emulsion (2) which is contained in a stabilizing container (3); wherein this stabilizing container (3) is an aluminum container, and the emulsion (2) consists of at least one prostaglandin, at least one oil selected from triglyceride oils, at least one cationic agent selected from quaternary ammonium compounds, at least one non-ionic surfactant selected from polysorbate and sorbitan esters, and water. Preferably, the emulsion (2) is also contained in at least one conditioning container (4), which is placed in the stabilizing container (3). The stabilizing container (3) may be in the form of a bag with two walls (5) joined together by a circumferential region (6). The invention relates to a package containing multiple kits (1).

Description

KIT FOR STABILISING PROSTAGLANDIN EMULSIONSFIELD OF INVENTION

[0001] The invention relates to a kit containing a stabilising container, the stabilising container containing an oil-in-water emulsion comprising at least one prostaglandin. Especially, the stabilising container is an aluminium container. The kit of the invention is useful, in particular, for stabilising emulsions for ophthalmic use.BACKGROUND OF INVENTION

[0002] Glaucoma causes damage to the optic nerve, leading to visual field loss, and remains the leading cause of irreversible blindness worldwide. Since the disease is generally progressive and irreversible, early detection and treatment to control the progression are crucial. Lowering intraocular pressure (IOP) is an effective means of avoiding damage to the optic nerve. The estimated number of patients globally in 2020 was 76 million, and this is expected to increase to 95 million by 2030. Prostaglandin Fiaipha and analogues thereof are known for their potency to reduce IOP. Especially, latanoprost reduces elevated IOP and is the most prescribed prostaglandin analogue in Europe.

[0003] WO 2006 / 050836 A2 and WO 2007 / 042262 A2 (NOVAGALI PHARMA SA) disclose cationic oil-in-water ophthalmic emulsions comprising a prostaglandin for use in the treatment of eye diseases or conditions, including ocular hypertension and glaucoma. The disclosed emulsions significantly increase the chemical stability of prostaglandins compared to commercial product “0.005% latanoprost ophthalmic solution” (Xalatan®, Pfizer, USA).

[0004] Ocular surface disease (OSD) represents an emerging problem in the management of glaucoma, with up to 60% of glaucoma patients having dry eye. OSD is a multifactorial ocular condition that may involve tear film degradation as well as damage to the ocular surface. It negatively influences quality of life and compromises adherence to glaucoma eye drop treatment, which can influence the efficacy of the therapy.

[0005] WO 2011 / 061298 Al (NOVAGALI PHARMA SA) discloses a composition comprising a prostaglandin Fiaipha or analogue, for use in the treatment of surface ocular conditions, including corneal and conjunctival lesions.

[0006] Although they represented at this time a very significant therapeutic improvement, the ophthalmic use of prostaglandins emulsions of the art was limited by practical issues. Indeed, it was unfortunately discovered that cationic oil-in-water emulsions comprising prostaglandins may be instable on storage, in particular the Applicant found out that exposure to light dramatically impacted the stability of such emulsions. Thus, there is still a need for means to ensure stability, in particular photostability, of ophthalmic vehicles for prostaglandin delivery to the eye.

[0007] The Applicant surprisingly found out that conditioning a cationic oil-in-water emulsion comprising a prostaglandin into a stabilising container that is an aluminium container (in particular an aluminium pouch), effectively prevented destabilisation of the emulsion. Stabilisation of the emulsion may be assessed through measurement of parameters such as, for example, pH, conductivity, amount of prostaglandin and / or amount of impurities. Thus, the Applicant hereby provides a kit according to the invention, comprising an aluminium container wherein the emulsion is conditioned. The invention opens the way to widespread use of cationic oil-in-water emulsions comprising prostaglandins for eye treatment, in particular for treatment of glaucoma, ocular hypertension or OSD.SUMMARY

[0008] The present invention relates to a kit containing an oil-in-water emulsion and a stabilising container; wherein the oil-in-water emulsion is contained into the stabilising container; wherein the stabilising container is an aluminium container; and wherein the oil-in-water emulsion comprises: at least one prostaglandin, at least one oil selected from triglyceride oils, at least one non-ionic surfactant selected from polysorbates and sorbitan esters, at least one cationic agent selected from quaternary ammonium compounds, and water.

[0009] According to one embodiment, the stabilising container is in the form of a pouch. According to one embodiment, the oil-in-water emulsion is further contained into a conditioning container, which is placed into the stabilising container. In one embodiment, the stabilising container comprises at least two of the conditioning containers, preferably at least five of the conditioning containers. In one embodiment, the conditioning container is a polyethylene container and / or a single-dose container, preferably a low-density polyethylene (LDPE) container.

[0010] According to one embodiment, the prostaglandin is selected from latanoprost, isopropyl unoprostone, travoprost, bimatoprost, and mixtures thereof; preferably the prostaglandin is latanoprost. According to one embodiment, the oil-in-water emulsion comprises: at least one prostaglandin comprising latanoprost, at least one oil comprising medium chain triglycerides, at least one non-ionic surfactant comprising polysorbate 80, at least one cationic agent comprising cetalkonium chloride, at least one osmotic agent comprising glycerol, and the water. According to one embodiment, the oil-in-water emulsion comprises from about 0.001 to 0.02% w / w of the at least one prostaglandin, from about 0.2 to 2.5% w / w of the at least one oil, from about 0.01 to 0.2% w / w of the at least one non-ionic surfactant, from about 0.001 to 0.02% w / w of the at least one cationic agent, from about 0.5 to 6% w / w of at least one osmotic agent, and from about 94 to 99% w / w of the water, in weight by total weight of the oil-in-water emulsion. In one embodiment, the oil-in-water emulsion comprises: about 0.005% w / w of latanoprost, about 1% w / w of medium chain triglycerides, about 0.05% w / w of polysorbate 80, about 0.005% w / w of cetalkonium chloride, about 2.4% w / w of glycerol, and water, in weight by total weight of the oil-in-water emulsion. According to one embodiment, the oil-in- water emulsion is an ophthalmic composition.

[0011] According to one embodiment, the oil-in-water emulsion is for use in the treatment of an eye disease or eye condition; preferably the eye disease or eye condition is glaucoma, ocular hypertension and / or ocular surface disease.

[0012] The present invention also relates to a pack comprising at least two kits according to the invention, preferably comprising 6, 12, 18 or 24 kits.

[0013] The present invention also relates to a method for manufacturing a kit according to the invention, wherein the method comprises the following step: conditioning an oil-in-water emulsion as defined hereinabove into a stabilising container and, optionally, a conditioning container, thereby obtaining the kit according to the invention; wherein the stabilising container is an aluminium container.

[0014] The present invention also relates to a method for stabilising an oil-in-water emulsion as defined as defined hereinabove, wherein the method comprises the following step: conditioning an oil-in-water emulsion as defined as defined hereinabove into a stabilising container and, optionally, a conditioning container, thereby stabilising the oil-in-water emulsion; wherein the stabilising container is an aluminium container.

[0015] The present invention also relates to a method for manufacturing a pack according to the invention, wherein the method comprises the following step: packaging together at least two kits according to the invention, thereby obtaining the pack according to the invention.DEFINITIONS

[0016] In the present invention, the following terms have the following meanings:

[0017] “About” is used herein to mean approximately, roughly, around, or in the region of. The term “about” preceding a figure means plus or less 10% of the value of said figure. When the term “about” is used in conjunction with a numerical range, it modifies that range by extending the boundaries above and below the numerical values set forth by 10 %.

[0018] “Active ingredient” and “therapeutic agent” or “pharmacologically active agent” are synonyms and refer to a compound for therapeutic use, and relates to health. Typically, an active ingredient presents a pharmaceutical effect and / or may be indicated for treating or preventing a disease or condition, as defined hereinafter. Preferably, the active ingredient is for use in the treatment of an eye disease or condition.

[0019] “Between [lower value] and [upper value]” and the like define a numerical range that excludes (z.e., does not encompass) both the upper value and the lower value.

[0020] “Droplet size” of an emulsion refers to the peak droplet size or the mean droplet size, preferably the peak droplet size, of the dispersed phase. Droplet size may be measured by methods known in the art, e.g., by light scattering after dilution in water using a High-Performance Particle Sizer (such as a Zetasizer 2000 or a Zetasizer Nano ZS, Malvern Instruments, UK).

[0021] “Emulsion”, in accordance with the general knowledge in the art, refers to a macroscopically homogeneous but microscopically heterogeneous mixture of two or more liquids that are normally immiscible owing to liquid-liquid phase separation. In an emulsion, one liquid (the “dispersed phase”) is dispersed in the other (the “continuous phase”) in the form of droplets. Stability of an emulsion is typically achieved by the inclusion of at least one surfactant in the emulsion. The surfactant may for example be present in the surface of the droplets of the emulsion.

[0022] “Oil-in-water emulsion” refers to an emulsion wherein the dispersed phase is significantly more lipophilic than the continuous phase. Typically, the dispersed phase is oil-based and / or the continuous phase is water-based.

[0023] “Ophthalmic composition” refers to a composition intended to be administered to the eye of a subject and / or which is suitable to be administered to the eye of a subject. Typically, an ophthalmic composition presents a pharmaceutical effect and / or may be indicated for treating an eye disease or condition.

[0024] “Ophthalmic treatment” refers to a treatment of an eye disease or condition in a subject in need thereof. Typically, an ophthalmic treatment comprises a step of administration of an ophthalmic composition as defined herein to the eye of a subject.

[0025] By “pharmaceutically acceptable” referring to a substance or a composition, it is meant that the substances or the composition are compatible with each other and / or not deleterious to the subject, preferably a human, to which the substance or composition is administered. Especially, it does not produce an adverse, allergic or other untowardreaction when administered to a subject, preferably a human. For human administration, compositions should meet sterility, pyrogenicity, general safety and purity standards as required by regulatory offices, such as, for example, Food and Drug Administration (FDA) Office or European Medicine Agency (EMA).

[0026] “Pharmaceutically acceptable excipient” refers to a pharmaceutically acceptable excipient, carrier or vehicle. It includes any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like.

[0027] “Pharmaceutical composition” refers to a composition comprising at least an active ingredient in association with at least a pharmaceutically acceptable excipient. A pharmaceutical composition is for therapeutic use, and relates to health. Especially, a pharmaceutical composition may be indicated for treating or preventing a disease or condition, as defined hereinafter. Preferably, a pharmaceutical composition is for use in the treatment of an eye disease or an eye condition.

[0028] “Prodrug” refers to an active ingredient that, after administration, is converted within the body (z.e., metabolized) into a drug (z.e., an active ingredient). Typical examples of prodrugs are ester, ether and amide derivatives of drugs.

[0029] “Prostaglandin” refers indifferently to prostaglandins, their derivatives, precursors, prodrugs and / or analogues, as well as pharmaceutically acceptable salts and / or solvates thereof.

[0030] “Quaternary ammonium compound” or “quaternary ammonium salt” are synonyms and refer to a salt of a quaternary ammonium cation.

[0031] “Ranging from [lower value] to [upper value]” and others similar recitations define a numerical range that includes (z.e., encompasses) both the upper value and the lower value. Moreover, any range so defined in the present application should be construed as including an explicit disclosure of the corresponding narrower range “between [lower value] and [upper value]”.

[0032] “Subject” refers to a warm-blooded animal, preferably a mammal, more preferably a human. Preferably, the subject is a patient, i.e., a subject who is awaiting the receipt of, or who is receiving medical care, or who is / will be the object of a medical procedure. Preferably, the subject is affected by an eye disease or an eye condition.

[0033] “Topical administration” refers to the administration of a composition onto the surface of an eye such as, for example, onto the cornea or the inner eyelid. Topical administration may for example be carried out by means of an eye dropper.

[0034] “Treating” or “treatment” or “alleviation” refers to both therapeutic treatment and prophylactic or preventative measures; wherein the object is to prevent or slow down (lessen) the targeted disease or condition in a subject in need thereof. Those in need of treatment include those already with the disease or condition as well as those prone to have the disorder or those in whom the disorder is to be prevented. A subject is successfully “treated” for a disease or condition if, after receiving a therapeutic amount of a substance or composition, the subject shows observable and / or measurable effect on one or more of the following: reduction in the number of pathogenic cells; reduction in the percent of total cells that are pathogenic; relief to some extent, of one or more of the symptoms associated with the specific disease or condition; reduced morbidity and mortality; and / or improvement in quality of life issues. The above parameters for assessing successful treatment and improvement in the disease are readily measurable by routine procedures familiar to a physician. Preferably, the treatment involves a step of administration of an active ingredient, as defined hereinabove. In the invention, the disease or condition is an eye disease or an eye condition, i.e., a pathologic disorder or a condition affecting the eye of a subject.

[0035] “Triglyceride” refers to a tri-ester derived from glycerol and exactly three fatty acids.

[0036] “Zeta potential” is defined as follows. One well-known approach in the art to stabilize an emulsion is to confer an electrostatic charge to the droplets surface of the dispersed phase, which will result in more droplet repulsion and less droplet coalescence. Colloidal particles dispersed in an emulsion are electrically charged due to their ioniccharacteristics and / or dipole attributes. This charge is referred to in the art as the “zeta potential” and it reflects the magnitude of the repulsion or attraction between particles. Zeta potential can be measured by methods known in the art, e.g., by measuring the electrophoretic mobility by means of a zetameter (such as a Zetasizer 2000 or Zetasizer Nano ZS, Malvern Instruments, UK). The electrophoretic mobility is the converted into zeta potential values through the Smoluchowsky or Henry equation.DETAILED DESCRIPTIONKit

[0037] The present invention relates to a kit containing an oil-in-water emulsion and a stabilising container; wherein the oil-in-water emulsion is contained in the stabilising container; wherein the stabilising container is an aluminium container; and wherein the oil-in-water emulsion comprises: at least one prostaglandin, at least one oil selected from triglyceride oils, at least one non-ionic surfactant selected from polysorbates and sorbitan esters, at least one cationic agent selected from quaternary ammonium compounds, and water.Stabilising container

[0038] The kit according to the invention comprises a stabilising container that forms an “intermediate container” or a “secondary packaging”, of which the main function is to stabilise the oil-in-water emulsion contained therein, compared to an emulsion not contained in the stabilising container.

[0039] In the invention, the stabilising container provides stabilisation of the emulsion. Advantageously, the stabilising container provides photo stability of the emulsion due to its opacity.

[0040] Advantageously, the emulsion is stabilised in terms of pH, for example, no significant decrease of the pH of the emulsion is observed during storage. Advantageously, the emulsion is stabilised in terms of conductivity, for example, no significant increase of the conductivity of the emulsion is observed during storage. Advantageously, the emulsion is stabilised in terms of amount of active ingredient, i.e., prostaglandin (prostaglandin assay), for example, no significant decrease of the amount of prostaglandin in the emulsion is observed during storage. Advantageously, the emulsion is stabilised in terms of amount of impurities (impurities assay), for example, no significant increase of the amount of impurities (e.g., degradation products of the prostaglandin) in the emulsion is observed during storage. Preferably, the emulsion is stabilised in terms of pH, conductivity, amount of prostaglandin (prostaglandin assay) and / or amount of impurities (impurities assay).

[0041] Advantageously, no significant decrease and / or increase of the osmolarity of the emulsion is observed during storage. Advantageously, no significant decrease and / or increase of the droplet size of the emulsion is observed during storage. Advantageously, no significant decrease and / or increase of the zeta potential of the emulsion is observed during storage.

[0042] Without being bound by any theory, the Applicant believes that decrease of the pH may be caused by the presence of acid degradation products in the emulsion and / or by water loss in the emulsion (i.e., concentration of the emulsion). In one embodiment, the acid degradation products comprise degradation product(s) of the prostaglandin (e.g., “acid- free latanoprost”, which is the active ingredient of which latanoprost is a prodrug) and / or degradation product(s) of at least one excipient (e.g., at least one free fatty acid resulting from the degradation of medium chain triglycerides (MCT)). Water loss can occur even when the emulsion is contained in a conditioning container (as described hereinafter), for example, water loss of an emulsion conditioned in an LDPE vial and not comprised in a closed pouch may be as high as 20% after about 3 years ofstorage in standard conditions. According to one embodiment, the water loss in the oil- in-water emulsion is equal to or lower than about 5% w / w, preferably equal to or lower than about 1% w / w, more preferably equal to or lower than about 0.5% w / w, more preferably equal to or lower than about 0.1% w / w, in weight by total weight of the oil-in- water emulsion (or in weight by total weight of water in the oil-in-water emulsion); after about 3 years of storage in standard conditions.

[0043] Stabilisation of the emulsion may be assessed, for example, through a photostability assays as described in Example 2 hereinbelow.

[0044] Advantageously, the emulsion is stabilised by the stabilising container for at least 6 months, preferably at least 1 year, more preferably at least 2 years, furthermore preferably at least 3 years; when stored in normal conditions such as, for example, about 25 °C and about 40% relative humidity (RH).

[0045] The stabilising container has peripheral walls delimiting a housing configured to receive the emulsion. The stabilising container is an aluminium container, i.e., at least an essential part, namely more than 50%, of the walls of the housing are covered by aluminium. For example, at least about 80% or about 90% or about 100% of a total surface of the walls of the housing are covered by aluminium. In the invention, “covered by aluminium” and the like encompasses embodiments wherein the walls are at least partially made of aluminium, so that a fraction of its surface is made of aluminium and thereby covered by aluminium, or, in the case of a multilayer housing, at least one layer comprises aluminium. The surface covered by aluminium may be further covered by a protective layer, such as, for example, a protective film, to avoid deterioration of the aluminium. In the invention, “aluminium” in the stabilising container is not limited to highly pure aluminium i.e., “elemental” aluminium, noted “Al”), but also encompasses any aluminium-based material known in the art or commercially available which comprises small amounts of impurities or additives required for preparation of the material, handling of the material, overtime stability, etc. Aluminium may be in different forms such as, for example, sheets or coatings. Aluminium may be, for example, applied on inner and / or outer surfaces of the walls, or included in a layer within the walls of the container.

[0046] The parts of the stabilising container that are not made of aluminium may be made, for example, of plastics (e.g., polymers, in particular polyolefins, or rubber), glass, metal, paper (e.g., cardboard), biomaterials, or any mixture and / or combination thereof.

[0047] In one preferred embodiment, the stabilising container is an aluminium-polyethylene container, i.e., a polyethylene-based container at least partially covered by aluminium (as defined hereinabove). The aluminium-polyethylene container may, for example, be a polyethylene-based container wherein at least about 80%, at least about 90% or about 100% of the total surface of the container is covered by aluminium. In one embodiment, the walls of the housing of the stabilising container comprise at least polyethylene terephthalate (PET), extruded ethylene methacrylic acid copolymer (“EXTR.PE”) and aluminium (“ALU”).

[0048] The stabilising container may be in different forms such as, for example, bags (e.g., pouches, sachets sacks, and the likes), boxes, ampoules, bottles, cans, flasks, jars, vials, and the likes. According to one embodiment, the stabilising container is in a form selected from bags (e.g., pouches), boxes, bottles, cans, and jars. In one preferred embodiment, the stabilising container is in the form of a pouch. A pouch may, for example, be made of two walls bonded together by a peripheric area closing at least partially the pouch around the housing. Typically, each of the walls can be formed of a flexible sheet, for example of a polygonal (especially rectangular) contour (including square sheets). Typically, the peripheric area extends along at least about 70% or about 75% or about 80% of the length of the side of the sheets. For example, if the sheets are rectangular, the peripheric area may extend along three sides of the sheets, preferably four sides of the sheets. Optionally, the pouch may further comprise a third sheet, typically a folded sheet, bonded along at least one side of each of the two sheets around the peripheric area, thereby increasing the internal volume of the pouch.

[0049] In one preferred embodiment, the stabilising container is an aluminium-polyethylene foil pouch.

[0050] According to a first embodiment, the stabilising container is open, z. e. , it includes at least one opening that represents a limited fraction of the total surface of the containersuch as, for example, less than about 30% or about 25% or about 20% of the total surface of the container.

[0051] According to a second embodiment, the stabilising container is closed, z.e., it includes either no opening or only openings that represents a negligeable fraction of the total surface of the stabilising container such as, for example, less than about 1% or about 0.1% or about 0.01% of the total surface of the stabilising container. Preferably, a closed stabilising container includes no opening. The stabilising container may be closed by any method known in the art such as, for example, by sealing the container. In one embodiment, the stabilising container is sealed. The stabilising container may be sealed by any method known in the art such as, for example, heat sealing (a sealing method which uses a combination of heat, time and pressure). The stabilizing container may comprise a sealable or reversible opening such as, for example, a zipper, to allow storage in a closed configuration and temporary opening during use.

[0052] In one embodiment, the stabilising container has a water vapour permeability equal to or lower than about 0.50 g / m2.day, preferably equal to or lower than about 0.25 g / m2.day, more preferably equal to or lower than about 0.05 g / m2.day (at about 23 °C and about 0% relative humidity (RH)). In one embodiment, the stabilising container has an oxygen permeability equal to or lower than about 0.50 cc / m2.day, preferably equal to or lower than about 0.25 cc / m2.day, more preferably equal to or lower than about 0.05 cc / m2.day (at about 38 °C and about 90% relative humidity (RH)).Conditioning container

[0053] According to one embodiment, the oil-in-water emulsion is further contained in a conditioning container, i.e., in the stabilising container is placed at least one conditioning container that forms an “internal container” or a “primary packaging”, which contains the emulsion. In the invention, the conditioning container is used to condition the emulsion, which includes, for example, keeping safely the emulsion overtime until it is used (e.g., until the ophthalmic treatment). Typically, the conditioning container encloses the emulsion, so that the emulsion is not directly in contact with the stabilising container, which is advantageous in terms of safety and durability, since the stabilisingcontainer comprises aluminium. The conditioning container may have additional functions such as, for example, allowing easy handling and / or administration of the emulsion (e.g., if the conditioning container is an eye drop) or maintaining the sterility of the emulsion.

[0054] The conditioning container may be made, for example, of plastics (e.g., polymers, in particular polyolefins, or rubber), glass, metal, paper (e.g., cardboard), biomaterials, or the likes, or any mixture and / or combination thereof. In one embodiment, the conditioning container is made of a material suitable for conditioning medicaments such as, for example, pharmaceutically acceptable polymers. In one embodiment, the conditioning container is partially or fully made of a transparent or translucent material. In one preferred embodiment, the conditioning container is a polyethylene container such as, for example, polyethylene terephthalate, high-density polyethylene (HDPE) or low-density polyethylene (LDPE). In one further preferred embodiment, the conditioning container is a low-density polyethylene (LDPE) container.

[0055] The conditioning container may extend along an extension axis between a bottom end and a dispensing end through which the emulsion may be dispensed. The conditioning container may be in different forms such as, for example, ampoules, bottles, cans, flasks, jars, vials, and the likes. According to one embodiment, the conditioning container is in a form selected from ampoules, bottles, flasks and vials. In one preferred embodiment, the conditioning container is in the form of a vial.

[0056] In one preferred embodiment, the conditioning container is in the form of a low-density polyethylene (LDPE) vial.

[0057] In one embodiment, the conditioning container is a single-dose container (or “single-use container”) or multidose container (or “multi-uses container”). In one preferred embodiment, the conditioning container is a single-dose container. The single-dose container may comprise, for example, from about 0.1 mL to about 0.5 mL of the emulsion, preferably from about 0.2 mL to about 0.4 mL of the emulsion, more preferably about 0.2 mL or about 0.3 mL of the emulsion. In one embodiment, thesingle-dose container comprises about 0.2 mL of the emulsion. In one embodiment, the single-dose container comprises about 0.3 mL of the emulsion.

[0058] In one embodiment, the conditioning container is an eye drop or eye dropper, so that its form allows for easy administration of the emulsion to the eye of a subject.

[0059] In one embodiment, the stabilising container contains at least two of the conditioning containers. In one embodiment, the stabilising container contains at least five of the conditioning containers. In one preferred embodiment, the stabilising container contains exactly five of the conditioning containers. In one preferred embodiment, the conditioning containers are bound to one another, e.g., the conditioning containers form together a strip in which the containers are adjacent to one another in a transverse direction perpendicular to the extension direction. Two adjacent containers of the strip are bound to each other by a frangible line between respective outer surfaces of their walls so that they can be separated before use. Such strip may be manufactured during the manufacturing process of the conditioning containers according to methods known in the art.

[0060] According to one preferred embodiment, the conditioning container is closed, i.e., it includes either no opening or only openings that represents a negligeable fraction of the total surface of the conditioning container such as, for example, less than about 1% or about 0.1% or about 0.01% of the total surface of the conditioning container. Preferably, a closed conditioning container includes no opening. The conditioning container may be closed by any method known in the art such as, for example, blow-fill- seal (BFS) technology. BFS is an automated manufacturing method for plastic containers, wherein the containers are blow-formed and filled, and sealed; the three steps being carried out in a continuous operation.Oil-in-water emulsion

[0061] In the invention, the triglyceride oil is comprised in the dispersed phase of the oil-in-water emulsion and the water is comprised in the continuous phase of the oil-in-water emulsion.

[0062] According to one embodiment, the triglyceride oil is the main component of the dispersed phase and water is the main component of the continuous phase. In this embodiment, according to a terminology of common use in the art, it may be indicated that the oil “is” the dispersed phase and water “is” the continuous phase, although the dispersed phase and the continuous phase may actually comprise further components solubilized or suspended therein such as, for example, active ingredients, surfactants, additives, etc.

[0063] Although some substances may possibly qualify simultaneously as an oil, a cationic agent and / or a non-ionic surfactant, in the emulsion according to the invention the oil, the cationic agent and the non-ionic surfactant refer to three different substances, z.e., in the emulsion of the invention the “oil” component cannot at the same time be the “non-ionic surfactant” component or the “cationic agent” component, etc. In others words, the emulsion of the invention systematically comprises at least three different substances in addition to water, at least one of them performing at least the function of the oil, another one of them performing at least the function of a non-ionic surfactant, and another one of them performing at least the function of the cationic agent. In others words, in the emulsion of the invention the oil, the cationic agent and the non-ionic surfactant are distinct substances to one another.

[0064] According to one embodiment, the prostaglandin is selected from latanoprost, isopropyl unoprostone, travoprost, bimatoprost, and mixtures thereof. In one particular embodiment, the prostaglandin comprises latanoprost. In one preferred embodiment, the prostaglandin substantially consists in, or consists in, latanoprost. In one embodiment, the emulsion comprises the prostaglandin in an amount ranging from about 0.001 to 0.02% w / w, preferably from about 0.002 to 0.01% w / w, more preferably about 0.005% w / w, in weight by total weight of the emulsion.

[0065] According to one embodiment, the triglyceride oil is present in the emulsion within an oil selected from vegetable oils, animal oils, and semi- synthetic oils obtained from vegetable and / or animal oils. In one embodiment, the triglyceride oil is a fractionated oil obtained from at least one vegetable oil, or a mixture thereof. According to one embodiment, the triglyceride oil, is selected from short chain triglycerides(z.e., Ci-Cs triglycerides), medium chain triglycerides (z.e., C6-C12 triglycerides), long chain triglycerides (z.e., C13-C21 triglycerides) or very long chain triglycerides (z.e., C22 or more, typically C22-C34 triglycerides). In one particular embodiment, the triglyceride oil comprises medium chain triglycerides (MCT). In one preferred embodiment, the triglyceride oil substantially consists in, or consists in, medium chain triglycerides (MCT). MCT may in particular be prepared from fractionated vegetable oils such as, for example, palm kernel oils or coconut oils. Typically, MCT density ranges from 0.93 to 0.96. In one embodiment, the emulsion comprises the oil in an amount ranging from about 0.2 to 2.5% w / w, preferably from about 0.5 to 1.5% w / w, more preferably about 1% w / w, in weight by total weight of the emulsion.

[0066] According to one preferred embodiment, the non-ionic surfactant is selected from polysorbates (trade name “Tween”) such as, for example, polysorbate 80 (trade name Tween® 80) or polysorbate 20 (trade name Tween® 20). Polysorbates are ethoxylated sorbitan esters. In one particular preferred embodiment, the non-ionic surfactant comprises polysorbate 80, such as, for example “super refined” commercial grade polysorbate 80. In one preferred embodiment, the non-ionic surfactant substantially consists in, or consists in, polysorbate 80. According to another embodiment, the non-ionic surfactant is selected from sorbitan esters (also known as “Spans”) such as, for example, Span™ 20, Span™ 40, Span™ 60, Span™ 65, Span™ 80 or Span™ 85. In one embodiment, the emulsion comprises the non-ionic surfactant in an amount ranging from about 0.01 to 0.2% w / w, preferably from about 0.02 to 0.1% w / w, more preferably about 0.05% w / w, in weight by total weight of the emulsion.

[0067] According to one embodiment, the quaternary ammonium compound is selected from cetalkonium halide, benzalkonium halide, lauralkonium halide, cetrimide, hexadecyltrimethylammonium halide, tetradecyltrimethylammonium halide, dodecyltrimethylammonium halide, cetrimonium halide, benzethonium halide, behenalkonium halide (or benzyldocosyldimethylammonium halide), cetethyldimonium halide, cetylpyridinium halide, benzododecinium halide, chloroallyl methenamine halide, myristalkonium halide (or benzyldimethyltetradecylammonium halide), stearalkonium halide or mixtures thereof. In one embodiment, the quaternary ammonium compoundcomprises cetalkonium halide. In one particular embodiment, the quaternary ammonium compound comprises cetalkonium chloride or bromide. In one further particular embodiment, the quaternary ammonium compound comprises cetalkonium chloride (CKC). In one preferred embodiment, the quaternary ammonium compound substantially consists in, or consists in, cetalkonium chloride (CKC). In one embodiment, the emulsion comprises the cationic agent in an amount ranging from about 0.001 to 0.02% w / w, preferably from about 0.002 to 0.01% w / w, more preferably about 0.005% w / w, in weight by total weight of the emulsion.

[0068] According to one embodiment, the water is selected from tap water, saline solution (saline), distilled water and ultrapure water. The water may be, for example, “water for injection” (also known as aqua ad iniectabilia or aqua ad inject ionein). In one embodiment, the emulsion comprises the water in an amount ranging from about 94 to 99% w / w, preferably from about 95 to 98% w / w, more preferably about 96.5% w / w, in weight by total weight of the emulsion. In one embodiment, the emulsion comprises the water in an amount sufficient to reach 100% w / w, based on the total amount of the ingredients of the emulsion that are not water (in weight by total weight of the emulsion), which may be noted “q.s. water”.

[0069] According to one embodiment, the emulsion comprises at least one osmotic agent. In one embodiment, the emulsion comprises at least one osmotic agent selected from glycerol (also known as glycerin or glycerine), mannitol, sorbitol, xylitol, propylene glycol, sodium chloride, potassium chloride, magnesium chloride, calcium chloride, and mixtures thereof. In one embodiment, the osmotic agent is selected from glycerol, mannitol, sorbitol and mixtures thereof. In one particular embodiment, the osmotic agent comprises glycerol. In one preferred embodiment, the osmotic agent substantially consists in, or consists in, glycerol. In one embodiment, the emulsion comprises the osmotic agent in an amount ranging from about 0.5 to 6% w / w, preferably from about 1 to 4% w / w, more preferably about 2.4% w / w, in weight by total weight of the emulsion.

[0070] The emulsion may further comprise at least one additive such as, for example, antioxidants, antimicrobials, buffers, chelating agents, pH adjusters, preservatives, solubilizers, stabilisers, thickening agents, viscosity modulator agents, or colorants.

[0071] According to one embodiment, the composition does not comprise a preservative agent selected from benzyl alcohol, boric acid, chlorhexidine, benzalkonium chloride (BAK), mercury salts, thiomersal, and mixtures thereof. In one embodiment, the emulsion is free of any preservative agent commonly used in pharmaceutical compositions (in particular, ophthalmic pharmaceutical compositions), i.e., the emulsion is “preservative-free”.

[0072] According to one embodiment, the oil-in-water emulsion comprises: at least one prostaglandin comprising latanoprost, and / or at least one oil comprising medium chain triglycerides (MCT), and / or at least one non-ionic surfactant comprising polysorbate 80, and / or at least one cationic agent comprising cetalkonium chloride (CKC), and / or at least one osmotic agent comprising glycerol, and the water.

[0073] In one embodiment, the oil-in-water emulsion comprises: at least one prostaglandin comprising latanoprost, at least one oil comprising medium chain triglycerides (MCT), at least one non-ionic surfactant comprising polysorbate 80, at least one cationic agent comprising cetalkonium chloride (CKC), at least one osmotic agent comprising glycerol, and the water.

[0074] According to one embodiment, the oil-in-water emulsion comprises: from about 0.001 to 0.02% w / w of the at least one prostaglandin, and / or from about 0.2 to 2.5% w / w of the at least one oil, and / or from about 0.01 to 0.2% w / w of the at least one non-ionic surfactant, and / or from about 0.001 to 0.02% w / w of the at least one cationic agent, and / or from about 0.5 to 6% w / w of at least one osmotic agent, and / or from about 94 to 99% w / w of the water (or q.s. water), in weight by total weight of the oil-in-water emulsion.

[0075] In one embodiment, the oil-in-water emulsion comprises: from about 0.001 to 0.02% w / w of the at least one prostaglandin, from about 0.2 to 2.5% w / w of the at least one oil, from about 0.01 to 0.2% w / w of the at least one non-ionic surfactant, from about 0.001 to 0.02% w / w of the at least one cationic agent, from about 0.5 to 6% w / w of at least one osmotic agent, and the water, preferably from about 94 to 99% w / w of the water (or q.s. water), in weight by total weight of the oil-in-water emulsion.

[0076] In one particular preferred embodiment, the oil-in-water emulsion comprises: from about 0.001 to 0.02% w / w of latanoprost, from about 0.2 to 2.5% w / w of medium chain triglycerides (MCT), from about 0.01 to 0.2% w / w of polysorbate 80, from about 0.001 to 0.02% w / w of cetalkonium chloride (CKC), from about 0.5 to 6% w / w of glycerol, and the water, preferably from about 94 to 99% w / w of the water (or q.s. water), in weight by total weight of the oil-in-water emulsion.

[0077] In one further preferred embodiment, the oil-in-water emulsion comprises: about 0.005% w / w of latanoprost, about 1% w / w of medium chain triglycerides (MCT), about 0.05% w / w of polysorbate 80, about 0.005% w / w of cetalkonium chloride (CKC), about 2.4% w / w of glycerol, and water, preferably about 96.5% w / w of water (or q.s. water), in weight by total weight of the oil-in-water emulsion.

[0078] According to one embodiment, the emulsion has a droplet size ranging from about 125 to 300 nm, preferably ranging from about 150 to 275 nm, more preferably ranging from about 175 to 225 nm. Droplet size of the emulsion may be adjusted to the desired values according to preparation methods for emulsion known in the art such as, for example, dispersion of the oily phase by means of magnetic stirring or use of ahomogenizer (e.g., POLYTRON® PT 6100 or MEGATRON® MT3100 (Kinematica), or Avestin® Emulsiflex C55 or Avestin® Emulsiflex Cl 60).

[0079] Advantageously, the emulsion is a cationic emulsion, i.e., an emulsion having a positive zeta potential, typically a zeta potential higher than or equal to 10 mV. In one embodiment, the cationic emulsion has a zeta potential higher than or equal to about 20 mV or about 30 mV or about 40 mV. In one embodiment, the cationic emulsion has a zeta potential ranging from about 20 to 75 mV, preferably ranging from about 30 to 65 mV, more preferably ranging from about 40 to 55 mV. Inclusion of a cationic agent in the emulsion (as described hereinabove) is a way to render it cationic by conferring it a positive charge.

[0080] Advantageously, the emulsion has a conductivity ranging from about 5 to 35 pS / cm, preferably ranging from about 10 to 30 pS / cm, more preferably ranging from about 15 to 25 pS / cm.

[0081] Advantageously, the emulsion has an osmolarity ranging from about 200 to 350 mOsm / kg, preferably ranging from about 250 to 300 mOsm / kg, more preferably ranging from about 270 to 285 mOsm / kg.

[0082] Advantageously, the emulsion has a pH ranging from about 3.5 to 6, preferably ranging from about 4 to 5.5, more preferably ranging from about 4.5 to 5.

[0083] The emulsion of the invention is advantageously sterilisable by methods known in the art, in accordance with safety requirements in the ophthalmic field. Especially, the emulsion keeps its structure and / or properties when sterilised. For example, the emulsion may be sterilisable by heat or steam sterilisation according to methods well-known in the art, preferably by heat sterilisation.Other kit embodiments

[0084] According to one embodiment, the kit further comprises instructions for use. In one embodiment, the instructions for use are printed on a leaflet e.g., a folded leaflet) or on a sticker. In one embodiment, the kit further comprises instructions for use that areplaced onto and / or into the stabilising container. In one embodiment, the instructions are for using the oil-in-water emulsion.

[0085] According to one embodiment, the kit further comprises at least one sticker. In one embodiment, the sticker is affixed onto the stabilising container and / or onto the conditioning container, preferably onto the conditioning container. According to one embodiment, the kit further comprises at least one printing. In one embodiment, the printing is applied onto the stabilising container and / or onto the conditioning container, preferably onto the stabilising container.Pack

[0086] The present invention also relates to a pack comprising at least one two kits according to the invention, as described hereinabove. In other words, the pack comprises “a plurality of’ kits according to the invention. According to one embodiment, the pack comprises 6, 12, 18 or 24 kits.

[0087] According to one embodiment, the pack comprises at least one packaging container that forms an “external container” or a “tertiary packaging”, in which the kits are comprised such as, for example, bags, boxes, or the likes.

[0088] According to one preferred embodiment, the pack further comprises instructions for use. In one embodiment, the instructions for use are printed on a leaflet (e.g., a folded leaflet) or on a sticker. In one embodiment, the pack further comprises instructions for use that are placed onto and / or into the packaging container. In one embodiment, the instructions are for using the oil-in-water emulsion.

[0089] According to one embodiment, the pack further comprises at least one sticker. In one embodiment, the sticker is affixed onto the packaging container. According to one embodiment, the pack further comprises at least one printing. In one embodiment, the printing is applied onto the packaging container.Medical uses

[0090] According to one embodiment, the oil-in-water emulsion comprised in the kit according to the invention, as described hereinabove, is for use as a medicament. According to one embodiment, the kit according to the invention, as described hereinabove, is for use as a medicament. According to one embodiment, the pack according to the invention, as described hereinabove, is for use as a medicament.

[0091] According to one embodiment, the emulsion, the kit and / or the pack is for use in the treatment of an eye disease or eye condition. In one preferred embodiment, the eye disease or eye condition is glaucoma, ocular hypertension and / or ocular surface disease (OSD). In one particular embodiment, the eye disease or eye condition is glaucoma such as, for example, open-angle glaucoma (also named “wide angle glaucoma” or “chronic simple glaucoma”), closed-angle glaucoma (also named “narrow angle glaucoma” or “acute congestive glaucoma”), or normal-tension glaucoma. In one further preferred embodiment, the glaucoma is open-angle glaucoma. In one particular embodiment, the eye disease or eye condition is ocular hypertension. In one particular embodiment, the eye disease or eye condition is an ocular surface disease (OSD) such as, for example, dry eye syndrome or blepharitis.

[0092] According to one embodiment, the emulsion is an ophthalmic composition. According to one embodiment, the emulsion is a pharmaceutical composition.

[0093] According to one embodiment, the kit and / or the pack is a medicament or a medicinal product.

[0094] According to one embodiment, the emulsion, as described hereinabove, is to be administered in a therapeutically effective amount to a subject in need thereof, in a method of treatment of an eye disease or eye condition. According to one embodiment, the kit and / or the pack according to the invention, as described hereinabove, is used in a method of treatment of an eye disease or eye condition.

[0095] According to one embodiment, the emulsion, as described hereinabove, is used in the manufacture of a medicament for the treatment of an eye disease or eye condition.According to one embodiment, the kit and / or the pack according to the invention, as described hereinabove, is used in the manufacture of a medicament for the treatment of an eye disease or eye condition.Method for manufacturing a kit and method of stabilising

[0096] The present invention also relates to a method for manufacturing a kit according to the invention, as described hereinabove, wherein the method comprises the following step: conditioning an oil-in-water emulsion, as described hereinabove, into a stabilising container, thereby obtaining the kit according to the invention; wherein the stabilising container is an aluminium container.

[0097] The present invention also relates to a method for stabilising an oil-in-water emulsion as described hereinabove, wherein the method comprises the following step: conditioning an oil-in-water emulsion as described hereinabove into a stabilising container, thereby stabilising the oil-in-water emulsion; wherein the stabilising container is an aluminium container.

[0098] According to an embodiment, the oil-in-water emulsion is contained into at least one conditioning container and the conditioning container is placed in the stabilising container.

[0099] According to an embodiment, the method for manufacturing a kit further comprises a step of conditioning the emulsion into at least one conditioning container.

[0100] Conditioning of the emulsion may, for example, include a step of pouring the emulsion into the stabilising container or conditioning container. Conditioning of the emulsion may optionally include at least one sterilisation step of the stabilising container and / or conditioning container, before and / or after the emulsion is placed into the container.

[0101] In the above methods, the oil-in-water emulsion, the stabilising container and / or the conditioning container may each independently be as described hereinabove in the embodiments of the kit according to the invention. “Stabilising” has the same meaning as described hereinabove in the embodiments of the kit according to the invention.Method for manufacturing a pack

[0102] The present invention also relates to a method for manufacturing a pack according to the invention, as described hereinabove, wherein the method comprises the following step: packaging together at least two kits according to the invention, as described hereinabove, thereby obtaining the pack according to the invention.

[0103] Packaging of the kits may, for example, include a step of packing together the kits with tape, paper, polymer film, or the likes. Packaging of the kits may also, for example, include a step of placing the kits together in a packaging container (or “external container” or “tertiary packaging”) such as, for example, bags, boxes, or the likes.BRIEF DESCRIPTION OF THE DRAWINGS

[0104] Figure 1 is a drawing showing a kit 1 according to the invention containing an oil-in-water emulsion 2 contained into one stabilising container 3.

[0105] Figure 2 is a drawing showing the kit of Figure 1, wherein the superior part of the stabilising container 3 has been removed.

[0106] Figure 3 is a drawing showing a detail of the kit of Figure 1, namely, an oil-in-water emulsion 2 contained into a conditioning container 4.

[0107] Figure 4 is a drawing showing an embodiment of the invention wherein the kit 1 contains five conditioning containers 4, which form together a strip 7.EXAMPLES

[0108] The invention is further illustrated by the following examples.Example 1: Oil-in-water emulsion and conditioning thereofMaterials and Methods

[0109] Materials: The ingredients used for the preparation of the oil-in-water emulsions were purchased from commercial providers and used without further purification. The aluminium pouches (stabilising containers) were made from sheets that were cut into a commercially purchased PET 12 pm / EXTR.PE 10 gsm / ALU 9 pm / EXTR.PE 30 gsm overwrap (CONSTANTIA TOBEPAL, Spain).

[0110] Methods - Heat sterilisation-. Heat sterilisation is performed in accordance with Ph.Eur 5.1.1 (e.g., European Pharmacopoeia section 5.0, section 5.1.1: “Methods of preparation of sterile products”) at a temperature of at least 121 °C during at least 15 min.

[0111] Methods - Manufacture of the oil-in-water emulsions: The oily and the water phases of the emulsion were separately prepared and heated to an appropriate temperature. The prostaglandin and cationic agent were dissolved into the oily phase. The non-ionic surfactant was dissolved into the aqueous phase. A first coarse emulsion was generated by magnetic stirring, and the droplet size was then reduced by high-shear mixing, high-pressure homogenization, or both. The resulting emulsion was sterilised after preparation using heat sterilisation.

[0112] Methods - Conditioning of the oil-in-water emulsions: After preparation, the emulsions were conditioned into low-density polyethylene (LDPE) vials (conditioning containers) by means of a conventional blow-fill- seal (BFS) process. Then, a strip of five polyethylene containers was placed into one aluminium pouch (stabilising container), which was closed, namely, sealed by heat sealing. Then, some of the aluminium pouches were open for comparative purposes. Some of the polyethylene containers were not pouched for comparative purposes.Results

[0113] The oil-in-water emulsion was prepared with the composition as shown inTable 1 below.Table 1

[0114] The oil-in-water emulsion Em#l is contained in a plurality of polyethylene vials placed into an aluminium pouch. The kit comprising the oil-in-water emulsion Em#l may be represented as shown on Figures 1-4.

[0115] In the embodiment represented on Figure 1, the kit 1 contains an oil-in-water emulsion 2 and a stabilising container 3 in the form of a rectangular pouch, in which the emulsion 2 is contained. The emulsion 2 is further comprised into a conditioning container 4 that is placed into the stabilising container 3. The stabilising container 3 has two walls 5 bonded together by a peripheric area 6 closing entirely the pouch around the housing, so that the pouch is closed. In this embodiment, the emulsion 2 is stabilised, as evidenced in Example 2 below.

[0116] In the embodiment represented on Figure 2, the superior part of the stabilising container 3 has been removed, so that the pouch is open. In this embodiment, the emulsion 2 is still stabilised, as evidenced in Example 2 below. Moreover, the conditioning container 4 can be removed from the stabilising container 3, so that the emulsion 2 can be administered to a subject in need thereof (not represented).

[0117] In the embodiment represented on Figure 3, the emulsion 2 is contained into a conditioning container 4 in the form of a vial. The vial comprises a housing, a neck and a removable cap. The conditioning container 4 is also in the form of an eye drop, so that it can be used to provide the emulsion 2 into the eye of a subject in need thereof (not shown).

[0118] In the embodiment represented on Figure 4, the emulsion 2 is contained into five conditioning containers 4 in the form of vials. The five conditioning containers 4 form together a strip 7.

[0119] After preparation (TO), the oil-in-water emulsion Em#l had the physical and chemical properties as indicated in Example 2 below.Example 2: Photostability assays

[0120] In this example are analysed the properties of an oil-in-water emulsion Em#l stored without pouch, into an open aluminium pouch, or into a closed aluminium pouch.Materials and Methods

[0121] Materials: pHmeter and conductimeter Mettler Toledo, microosmometer Roebling 13 / 13 / DR or Loser Type 16, and ZetaSizer Nano ZS Malvern.

[0122] Methods - pH and conductivity measurement'. The test is performed in accordance with Ph.Eur 2.2.3 (e.g., European Pharmacopoeia section 5.0, 2.2.3: “Potentiometric determination of pH”) using a potentiometric method and the pHmeter and conductimeter Mettler Toledo at a temperature from 20 to 25 °C.

[0123] Methods - Osmolarity measurement: The test is performed in accordance to Ph.Eur 2.2.35 (e.g., European Pharmacopoeia 7.3, section 2.2.35: “Osmolality”) using a cryoscopic method and the microosmometer.

[0124] Methods - Zeta potential measurement: The zeta potential of the emulsion droplet is determined by electrophoretic mobility measurement using the ZetaSizer Nano ZS Malvern. Measurement is performed on a sample of the emulsion diluted at 1:250 in deionized water.

[0125] Methods - Droplet size measurement: The droplet diameter of the oil droplet is determined by dynamic light scattering using the ZetaSizer Nano ZS Malvern. Measurement is performed on a sample of emulsion diluted at 1:20 in deionized water.

[0126] Methods - Prostaglandin assay. Determination of the amount of prostaglandin (in particular latanoprost) is determined by High-Performance Liquid Chromatography (HPCL) in reverse phase conditions by using C18 silica chromatographic column as stationary phase and UV detection. The samples are prepared by simple dilution in deionized water.

[0127] Methods - Impurities assay. Determination of impurities (including degradation products of prostaglandin) is performed by a High-Performance Liquid Chromatography (HPLC) method in normal phase conditions by using a pure silica chromatographic column as stationary phase and UV detection. The samples are prepared by solid-liquid extraction (Solid Phase Extraction or SPE).ResultsPhysical tests

[0128] The physical properties of the oil-in-water emulsion were as shown in Table 2 below.Table 2

[0129] The physical properties of the oil-in-water emulsion Em#l stay stable when the emulsion in the conditioning containers is pouched, even when the pouch is opened. By contrast, they significantly change when the emulsion is not pouched: pH decreases (about 13%) and conductivity dramatically increases (about 150%). Osmolality, zeta potential and droplet size remain relatively stable whether the emulsion is pouched or not. Therefore, both the open or closed aluminium pouch stabilise the emulsion Em#l.Prostaglandin assay

[0130] The results of the prostaglandin assay are shown in Table 3 below.Table 3

[0131] The prostaglandin assays were replicated one time. The values indicated on Table 3 above are the means values obtained from the two assays.

[0132] The amount of latanoprost in the oil-in-water emulsion Em#l stays stable when the emulsion in the conditioning containers is pouched, even when the pouch is opened. By contrast, it decreases significantly when the emulsion is not pouched (about 4% decrease). Therefore, both the open or closed aluminium pouch stabilises the emulsion Em#l.Impurities assay

[0133] The results of the impurities assay are shown in Table 4 below.Table 4

[0134] “<LOQ” means “limit of quantification” and “ND” means “not detected”.

[0135] The amount of impurities in the oil-in-water emulsion Em#l stays relatively stable when the emulsion in the conditioning containers is pouched, even when the pouch is opened. By contrast, it increases significantly when the emulsion is not pouched, with a more than 3-fold increase. Therefore, both the open or closed aluminium pouch stabilises the emulsion Em#l.

Claims

CLAIMS1. Kit (1) containing an oil-in-water emulsion (2) and a stabilising container (3); wherein said oil-in-water emulsion (2) is contained into said stabilising container (3); wherein said stabilising container (3) is an aluminium container; and wherein said oil-in-water emulsion (2) comprises: at least one prostaglandin, at least one oil selected from triglyceride oils, at least one non-ionic surfactant selected from polysorbates and sorbitan esters, at least one cationic agent selected from quaternary ammonium compounds, and water.

2. The kit according to claim 1, wherein said stabilising container (3) is in the form of a pouch.

3. The kit according to claim 1 or claim 2, wherein said oil-in-water emulsion (2) is further contained into a conditioning container (4), which is placed into said stabilising container (3).

4. The kit according to claim 3, wherein said stabilising container (3) comprises at least two of said conditioning containers (4), preferably at least five of said conditioning containers (4).

5. The kit according to claim 3 or claim 4, wherein said conditioning container (4) is a polyethylene container and / or a single-dose container, preferably a low-density polyethylene (LDPE) container.

6. The kit according to any one of claims 1 to 5, wherein said prostaglandin is selected from latanoprost, isopropyl unoprostone, travoprost, bimatoprost, and mixtures thereof; preferably said prostaglandin is latanoprost.

7. The kit according to any one of claims 1 to 6, wherein said oil-in-water emulsion (2) comprises: at least one prostaglandin comprising latanoprost, at least one oil comprising medium chain triglycerides, at least one non-ionic surfactant comprising polysorbate 80, at least one cationic agent comprising cetalkonium chloride, at least one osmotic agent comprising glycerol, and said water.

8. The kit according to any one of claims 1 to 7, wherein said oil-in-water emulsion (2) comprises: from about 0.001 to 0.02% w / w of said at least one prostaglandin, from about 0.2 to 2.5% w / w of said at least one oil, from about 0.01 to 0.2% w / w of said at least one non-ionic surfactant, from about 0.001 to 0.02% w / w of said at least one cationic agent, from about 0.5 to 6% w / w of at least one osmotic agent, and from about 94 to 99% w / w of said water, in weight by total weight of said oil-in-water emulsion.

9. The kit according to any one of claims 1 to 8, wherein said oil-in-water emulsion (2) comprises: about 0.005% w / w of latanoprost, about 1% w / w of medium chain triglycerides, about 0.05% w / w of polysorbate 80, about 0.005% w / w of cetalkonium chloride, about 2.4% w / w of glycerol, and water, in weight by total weight of said oil-in-water emulsion.

10. The kit according to any one of claims 1 to 9, wherein said oil-in-water emulsion (2) is an ophthalmic composition.

11. The kit according to any one of claims 1 to 10, wherein said oil-in-water emulsion (2) is for use in the treatment of an eye disease or eye condition; preferably said eye disease or eye condition is glaucoma, ocular hypertension and / or ocular surface disease.

12. Pack comprising at least two kits (1) according to any one of claims 1 to 11, preferably comprising 6, 12, 18 or 24 kits (1).

13. Method for manufacturing a kit (1) according to any one of claims 1 to 11, wherein said method comprises the following step:- conditioning an oil-in-water emulsion (2) as defined in any one of claims 1 to 11 into a stabilising container (3) and, optionally, a conditioning container (4), thereby obtaining the kit (1) according to any one of claims 1 to 11; wherein said stabilising container (3) is an aluminium container.

14. Method for stabilising an oil-in-water emulsion (2) as defined in any one of claims 1 to 11, wherein said method comprises the following step:- conditioning an oil-in-water emulsion (2) as defined in any one of claims 1 to 11 into a stabilising container (3) and, optionally, a conditioning container (4), thereby stabilising said oil-in-water emulsion (2); wherein said stabilising container (3) is an aluminium container.

15. Method for manufacturing a pack according to claim 12, wherein said method comprises the following step:- packaging together at least two kits (1) according to any one of claims 1 to 11, thereby obtaining the pack according to claim 12.

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