Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/0012—Galenical forms characterised by the site of application
  • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
  • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
  • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/10—Dispersions; Emulsions
  • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
  • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
  • A61K9/143—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with inorganic compounds
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
  • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
  • A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
  • A61P17/04—Antipruritics

Definitions

• the present invention relates to topical (dermal) pharmaceutical formulations for the treatment of pruritus (itching).
• the formulations are biphasic, containing an aqueous phase and a lipophilic phase, and at least one of the phases contains particles insoluble in that phase, that provide texture to relieve itching, that dissolve in the other phase.
• W02008038807A1 discloses topical formulations comprising butylhydroxytoluene. No second phase or second type of particles are described.
• W02009087578A2 discloses an emollient emulsion foam comprising menthol. Based on the above-mentioned state of the art, the objective of the present invention is to provide means and methods to treat pruritus. This objective is attained by the subject-matter of the independent claims of the present specification, with further advantageous embodiments set out in the dependent claims.
• treating or treatment of any disease or disorder refers in one embodiment, to ameliorating the disease or disorder (e.g. slowing or arresting or reducing the development of the disease or at least one of the clinical symptoms thereof).
• treating or treatment refers to alleviating or ameliorating at least one physical parameter including those which may not be discernible by the patient.
• treating or treatment refers to modulating the disease or disorder, either physically, (e.g., stabilization of a discernible symptom), physiologically, (e.g., stabilization of a physical parameter), or both.
• pruritus as used in the context of the invention is defined as an unpleasant sensation, often in the skin, which provokes the urge to scratch. Often referred to as “itch”, pruritus is a characteristic feature of many skin diseases, but can also have, immunologic, neurological or systemic origins. Pruritus can be local or generalised, and can be a chronic or an acute condition.
• a first aspect of the invention relates to a composition for topical administration, comprising, or in certain embodiments, consisting of two phases, a hydrophilic phase which contains at least one type of granules or particles, in addition to a lipophilic phase.
• phase refers to a vehicle for the topical administration of a treatment substance to the skin, in other words, a gel, an ointment, or a cream.
• a gel an emulsion made of up gelling agents, particularly useful in the delivery of hydrophobic drugs.
• An emulsion can be generated by the composition according to the invention. It is understood that the topical composition however is provided in a state where two phases are separate and the emulsion is created by the patient, or a caretaker, in the act of applying or administering the composition.
• An alternative of this first aspect of the invention relates to a topical composition
• a topical composition comprising a hydrophilic phase and a lipophilic phase provided as two separate phases prior to topical administration, each phase comprising particles, wherein a hydrophilic phase comprises first particles, and wherein a lipophilic phase comprises second particles.
• the first particles are stably particular, i.e. insoluble in the hydrophilic phase, but are soluble in the lipophilic phase.
• the second particles are stably particular, i.e. insoluble in the lipophilic phase, but are soluble in the hydrophilic phase.
• the topical composition comprises a hydrophilic phase and a lipophilic phase provided as two separate phases prior to topical administration, the hydrophilic phase comprises first particles that comprise or essentially consist of menthol, and the lipophilic phase comprises second particles that comprise or essentially consist of a water soluble salt.
• particle in the context of the invention encompasses a substance or pharmaceutical formulation in a solid, or crystalline form, such that the particles are of sufficient size to provide a granular, lightly abrasive texture to the composition.
• the particles suspended within the hydrophilic vehicle should be lipophilic, i.e. tending to dissolve in lipids or fats rather than water-based media, and therefore will not dissolve when stored within the hydrophilic phase of the topical composition according to the invention.
• non-polar particles suspended in the hydrophilic phase provide a granular, or lightly abrasive texture.
• An important aspect of the invention is combination of the hydrophilic phase containing a lipophilic particle, and the lipophilic phase during topical administration. These two vehicles will mix when the composition containing the two phases is applied topically, for example by rubbing into the skin.
• This aspect of the invention serves the dual purpose of delivering a pleasant sensation of scratching an itch, while at the same time performing a manual mixing process allowing medicaments contained in the granules to be absorbed into skin when the lipophilic particles dissolve in the lipophilic phase.
• This aspect of the invention is also important for the topical composition to be non-occlusive, providing acute relief without needed to be wiped away.
• the lipophilic phase of the topical composition comprises, or in some cases, also contains particles, allowing additional textural or medicinal components to be included in the formulation.
• the particles suspended within the hydrophilic phase of the topical composition comprise, or may essentially consist of menthol.
• Menthol has the advantages of providing, in addition to the textural quality, a pharmaceutical quality in that it has analgesic properties and provides a sensation of cooling due to its interaction with temperature sensitive receptors on skin cells.
• the particles suspended within either phase of the topical composition are characterized by a mean particle size of 200 - 2000 pm.
• the particles suspended within either phase of the topical composition are characterized by a mean particle size of 800 - 2000 pm.
• the particles suspended within either phase of the topical composition are characterized by a mean particle size of 200 - 1000 pm. In certain particular embodiments, the particles suspended within either phase of the topical composition are characterized by a mean particle size of 400 to 1200 pm.
• the particles suspended within either phase of the topical composition are characterized by a mean particle size of more particularly by a particle size of 400 to 800 pm.
• the particles suspended within either phase of the topical composition are characterized by a mean particle size of 500 - 750 pm.
• the second particles suspended in the lipophilic phase comprise, or in certain embodiments essentially consist of a water soluble particle, which will not dissolve in the lipophilic vehicle and can therefore add an additional scratching sensation during application to the skin, until the point at which it dissolves when mixed with the hydrophilic phase.
• the water soluble particle is a water soluble salt, more particularly a water soluble salt of a first or second group (alkali, earth alkali) element.
• the lipophilic phase of the topical composition according to the invention contains, or in certain embodiments comprises sodium chloride (NaCI), potassium chloride (KCI), magnesium chloride (MgCh), calcium hydrogen phosphate CahfePO ⁇ or CaH(P04)2, or another water soluble salt with the desired particle size and non-irritant qualities that suit topical administration.
• NaCI sodium chloride
• KCI potassium chloride
• MgCh magnesium chloride
• CahfePO ⁇ calcium hydrogen phosphate CahfePO ⁇ or CaH(P04)2
• another water soluble salt with the desired particle size and non-irritant qualities that suit topical administration.
• the data in the examples demonstrates that the water soluble salt NaCI persists as granules when stored in the lyophilic media, and dissolves on coming into contact with the hydrophilic phase during topical administration, providing additional textural stimulation during the process of application.
• menthol particles for addition to the hydrophilic phase are characterized by a mean particle size of 500 - 750 pm.
• the first particles are characterized by a mean particle size of 200 - 1000 pm.
• the second particles are characterized by a mean particle size of 200 - 1000 pm.
• the first particles are characterized by a mean particle size of 400 to 800 pm, particularly by a particle size of 500 - 750 pm.
• the second particles are characterized by a mean particle size of 400 to 800 pm, particularly by a particle size of 500 - 750 pm.
• the first particles are menthol particles characterized by a mean particle size of 500 - 750 pm.
• the lipophilic phase which may or may not contain additional particles, comprises, or in some cases essentially consists of long chain waxy esters.
• a particularly desirable embodiment of the topical composition is one in which the lipophilic phase comprises or essentially consists of lanolin.
• lanolin as used here is meant to encompass high-purity, acetylated lanolin as commonly used in formulations for topical administration, sometimes referred to in the description as “Wollwachsalkoholsalbe”. It should be understood that other hydrophobic gels for topical administration would be equally effective, such as acetate, silicone or oil-based gels.
• acetylated lanolin is an effective vehicle for the suspension of NaCI particles, in order to deliver a scratching sensation during administration, while at the same time effectively dissolved the lipophilic menthol particles contained in the composition.
• the hydrophilic phase comprises a hydrogel forming polymer, and may further comprise a buffer system, chelating agents for preservation, and excipients suitable for dermal application.
• the hydrogel forming polymer is selected from galactomannan, kappa-carrageenan, alginate, alginate sulfate, cellulose, methylcellulose, ethylcellulose, bacterial cellulose, carrageenan, carrageenan sulfate, cellulose acetate, chitosan, chondroitin sulfate, dextran, hydroxypropyl dextran, fucan sulfate, gelatin, gellan gum, acylated and/or sulfated gellan gum, guar gum, gellan sulfate, cassia gum, konjac gum, Arabic gum, ghatti gum, locust bean gum, heparin, heparan sulfate, hyaluronan, hyaluronan sulfate, mannuronan, pectin, starch, hydroxypropyl starch, ulvan (sulfated xylor
• the hydrophilic phase is a hydrogel which comprises the polymer carbomer (polyacrylate), particularly carbomer 35 000, and in addition may comprise one or more of trometamol (Tris), sodium EDTA (edetate disodium), and/or propylene glycol.
• Carbomer 35000 is an example of a 2-propenoic acid homopolymer which can be used in the manufacture of a hydrogel with desirable hydrophilic features.
• Carmellose sodium, hydroxypropylcellulose and other cellulose derivatives are further examples of well-known polymers that can form hydrogels.
• hydrogel as described in the in examples could be substituted by any similar hydrophilic media for topical administration.
• a hydrogel is a network of hydrophilic polymers that can incorporate large amounts of water: Examples of hydrogels currently available for use in gels for topical administration include Hypan (Hymedix International, USA), Smart Hydrogel (MedLogic Global, UK), Aquamere and Aquatrix II (Hydromer, USA).
• an anaesthetic and/or antihistamine is included as part of the formulation, to assist in the relief of itching.
• One particular anaesthetic that is desirable for incorporation into the composition according to the invention is polidocanol.
• the additional medicament incorporated into the formulation could be lidocaine, benzocaine, capsaicin, or other medicaments that are used for topical treatment of pruritus.
• the hydrophilic phase used as vehicle for menthol particles is a hydrogel, such as “carbomagel” made by combining carbomer 35000, trometamol, sodium EDTA, and propylene glycol, combined with polidocanol at an appropriate dose to deliver topical anaesthesia.
• This composition successfully incorporated menthol particles without dissolving until mixed with the additional lipophilic phase.
• a different antipruritic medication is incorporated into the formulation, for example it includes one or more of a corticosteroid, camphor, mint oil, etheric oils, and/or crotamiton.
• a corticosteroid that may be desirable for addition to the topical administration is hydrocortisone acetate.
• An example of an anti-itching crotamiton (CAS No 483-63-6) medication is Eurax (GSK, UK).
• the anti-pruritus formulation according to the invention comprises a non-steroidal anti-inflammatory agent, particularly diclofenac particles.
• the topical composition according to the invention is used as a treatment for a subject who suffers from pruritus.
• the different phases of the topical composition according to the invention are stored in, and/or applied from separate tubes, in order to keep the lipophilic and hydrophilic components separate.
• the topical composition is applied from a vessel containing separated chambers, where the lipophilic phase is stored in a first chamber and the hydrophilic phase is stored in a second chamber of, for example, a tube separated with one or several dividers.
• the phases emit from separate nozzles from their respective chambers, and are combined once administered to the skin.
• the composition is administered from a dual-chambered, squeezable tube, or a dual chambered tube.
• a dual-chambered, squeezable tube or a dual chambered tube.
• Different designs have been proposed for dual chamber administration systems for pharmaceutical or cosmetic formulations; these include designs described by US2004173632 (A1 ), US7435027B2, US8413845B1 , all of which are incorporated herein by reference.
• the pharmaceutical composition is formulated in a way that is suitable for topical administration such as aqueous solutions, suspensions, ointments, creams, gels or sprayable formulations, e.g., for delivery by aerosol or the like, comprising the active ingredient together with one or more of solubilizers, stabilizers, tonicity enhancing agents, buffers and preservatives that are known to those skilled in the art.
• a topical composition comprising
• hydrophilic phase comprises first particles
• Item 2 The topical composition according to item 1 , wherein the lipophilic phase comprises second particles.
• Item 3 The topical composition according to item 1 or 2, wherein the first particles comprise or essentially consist of menthol.
• Item 4 The topical composition according to any one of the preceding items, wherein the first and/or second particles are characterized by a mean particle size of 200 - 1000 pm, particularly 400 to 800 pm, more particularly by a particle size of 500 - 750 pm.
• Item 5. The topical composition according to any one of the preceding items, wherein the first particles are menthol particles characterized by a mean particle size of 500 - 750 pm.
• Item 6 The topical composition according to any one of the preceding items, wherein the second particles comprise or essentially consist of a water soluble salt.
• Item 7 The topical composition according to item 6, wherein the water soluble salt is selected from: NaCI, MgCh, KCI, NaHCOs, CahbPC , CaH(P04)2.
• Item 8 The topical composition according to any one of the preceding items, wherein the lipophilic phase comprises or essentially consists of, in addition to the second particles, long chain waxy esters, particularly wherein the long chain waxy esters comprise or essentially consist of lanolin.
• Item 9 The topical composition according to any one of the preceding items, wherein the hydrophilic phase comprises one or more of: carbomer 35000, trometamol, sodium EDTA, propylene glycol.
• the hydrophilic phase comprises one or more of: carbomer 35000, trometamol, sodium EDTA, propylene glycol.
• Item 10 The topical composition according to any one of the preceding items, comprising an anaesthetic and/or antihistamine.
• Item 11 The topical composition according to any one of the preceding items, wherein the anaesthetic is polidocanol.
• Item 12 The topical composition according to any one of the preceding items, comprising one or more of: a corticosteroid, camphor, mint oil, etheric oils, or crotamiton.
• Item 13 An administration form comprising a topical composition according to any one of the preceding items, wherein the lipophilic phase is disposed in a first chamber and the hydrophilic phase is disposed in a second chamber.
• Item 14 The administration form according to item 14, wherein the administration form is arranged as a dual set of squeeze tubes, or a dual chamber tube.
• Item 15 The topical composition or the administration form according to any one of the preceding items for use in treatment of pruritus.
• the invention is further illustrated by the following examples, from which further embodiments and advantages can be drawn. These examples are meant to illustrate the invention but not to limit its scope.
• Example 1 Hydrophilic composition containing menthol Hydrophilic phase vehicle
• Menthol crystals were chosen as the particle to deliver a rough texture to the hydrophilic vehicle, as they have well-described antipruritic and confer a cooling, soothing sensation.
• the menthol was provided in the form of large, elongate crystals, which were considered inappropriate for the formulation due to their sharp ends which could abrade the skin.
• the menthol particles were crushed to smaller particles, and those within the range of 500-710 micrometres were isolated by filtration with mesh filters.
• the hydrophobic menthol particles did not dissolve in the hydrophilic vehicle, successfully forming a gel with suspended menthol particles, capable of provided a texture supporting a scratching sensation.
• Example 2 Hydrophilic composition containing menthol and an antipruritic medication.
• Amitryptilin in a granulated form derived from capsule dosage was first considered as an additional component of the formulation.
• amitryptilin granules to the Hydrophilic phase with menthol from example 1
• amitryptilin proved to have desirable hydrophobic qualities which led to the formation of a suspension containing particles capable of providing a scratching sensation when applied to skin.
• dissolving the amitryptilin to deliver a medical dose to the subject requires a high alkaline pH. This was incompatible with topical administration to the current application for human skin due to the acidity of the carbomergel pH 5 preparation.
• latest guidelines no longer recommend topical application of antihistamines for pruritus treatment.
• amitriptyline a substance with antihistaminic properties, was deprioritized for the development of the formulation.
• polidocanol was then considered for addition to the hydrophilic phase.
• This surfactant can deliver moisturizing and anaesthetic properties, which have been found to significantly reduce pruritus when applied topically (Freitag G. et al. 1997, Curr. Med. Res. and Op. 13(9):529.37). It is mostly prescribed in sclerotherapy, but can also be applied externally.
• polidocanol 3% combined with urea 5% was found to significantly reduce pruritus (Freitag G. ibid.).
• the European Guideline on Chronic Pruritus recommends the use of polidocanol at 2-10% (Weisshaar E. et al. Acta Dermato- venereologica 2012. 92(5):508-14).
• the composition was formed by adding polidocanol liquid to the hydrophilic phase with menthol, with mixing, in a mortar and pestle to provide a homogenous gel in the following proportions:
• menthol crystals for the preparation of a hydrophilic composition containing menthol in Example 1 , was limited to the chosen dosage in order to avoid the possibility of skin irritation at high menthol concentrations. However, this amount of menthol failed to provide a sufficiently granular texture to provide the sensation of scratching when applied to skin.
• NaCI was tested as an additional non-irritant, particle ingredient. As sodium chloride is hydrophilic, acetylated lanolin was tested as a hydrophobic media, with additional moisturizing qualities.
• NaCI powder formed a uniform paste when combined with acetylated lanolin, and the particles did not dissolve.
• Example 4 A two phase formulation to provide a topical scratching effect.
• the chosen particles one of which being menthol, an antipruritic agent itself, were stored in a septum divided tube, containing a hydrophobic and a hydrophilic vehicle. Only when applied to the skin, do the individual components mix, initializing a scratch effect until the individual particles dissolve in the respective opposite phase without harming the skin.
• the result is an anti-pruritic emulgel containing two particle types of a dull, non-damaging, granular structure, which prevents skin excoriation, but at the same time mimics the instantaneous feeling of relief brought about by scratching.
• This substance is a novel topical treatment strategy to break the itch-scratch cycle. It offers an alternative approach to the already existing manifold, yet deficient topical treatment in chronic pruritus.
• Methanol In topical formulations for itch relief, methanol is a key feature. Methanol, which is contained in the formulation in particle form and, after application, first provides relief through a mechanical effect of blunt friction, followed by a direct anti-pruritic effect of the menthol after dissolution of the menthol crystals.
• One phase contained menthol crystals in stable suspension, the other phase is an emulsion that causes dissolution of the menthol after mixing.
• good stability was demonstrated in 24 weeks stability studies.
• NaCI sodium chloride
• Oleogels are lipophilic, typically water-free, bi-coherent systems consisting of an oil phase and a coherent structure-building phase that may consist of polymers or network structures formed from low molecular weight consistency agents.
• a typical polymer is ethyl cellulose, however, it needs to be used in concentrations of several percent and leaves a water-insoluble film on the skin rendering it cosmetically unfavorable.
• Low molecular weight consistency agents include monoacyl glycerides, in particular glycerol monostearate, fatty acids and fatty alcohols, aluminium stearate, or lecithin.
• inorganic materials like fused silica or bentonites are used. The inorganic materials are typically cosmetically less favorable, and lecithin requires the presence of a certain amount of water. Therefore, glycerol monostearate was selected as the primary consistency agent.
• the lanolin substitute Softisan 649 bis- diglyceryl polyacyladipate-2) was investigated.
• a further benefit of this excipient which is frequently used in cosmetic formulations, is its ability to take up water which makes it favorable for the mixing with the water phase.
• Table 1 shows the composition of the initial oleogel base formulations. All ingredients are INCI listed and frequently used in cosmetics. Oleogels were characterized macroscopically, microscopically and by shear rheometry 14 days after manufacturing (stored at room temperature).
• the oleogels will be mixed with the aqueous gel phase, the mixture should ideally result in a cosmetically pleasant emulsion.
• emulsifiers would (partially) dissolve the menthol in the water phase, they needed to be integrated in the oil phase.
• the mixing behavior of all three oleogel base formulations with the gel phases F006 and F007 was investigated. As shown for F006 and the oleogels in all cases an emulsion was easily achieved (also when mixed with F007). F001 with the hydrophilic O/W emulsifier will form an O/W emulsion as soon as a high enough ratio of water is provided.
• phase transition from an initial W/O emulsion to a O/W emulsion occurs.
• O/W emulsions can more easily be washed off and appear less greasy than W/O emulsions.
• F002 and F003 will form W/O emulsions.
• phase transition will not occur, unless a huge excess of water is provided.
• F001 and F002 were selected for the development of the suspension formulations. In addition, it was decided to include a suspension in a Pharm. Eur. petrolatum base for comparison.
• the oleogels showed a homogeneous appearance which was confirmed in the microscopic image.
• the appearance in the polarized mode was slightly different to the NaCI-free base formulations (As the crystal sizes are larger than the images sections, crystal-free parts of the formulations were selected).
• the petrolatum-based ointment showed a coarser structure.
• the physical stability of the formulations was investigated in a short-term stability study for 6 weeks at 5°C, 25°C and cycling conditions (from -5°C to 40°C in 24h cycles). In the macroscopic examination, no signs of instability were observed at any condition, especially no signs of sedimentation or phase separation. Also, in the microscopic image no significant changes occurred. As the cycling test represents a strong stress to formulations, these results are encouraging for long-term stability.
• oleogel NaCI suspensions as oil phase of the itch relief product were successfully developed.
• the rheological profile was favorable and the selected oleogels F001 and F002 mix well with the aqueous gel phase to form an emulsion.
• a 6-weeks stability showed good stability, even at stress conditions so that it is likely that long-term stability could be confirmed in a respective study.
• the developed oleogels appear to be well suited for the purpose of the itch relief product.

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