Pharmaceutical carrier and pharmaceutical composition comprising the same

Abstract

The present invention relates to the technical field of pharmaceutical carriers or bases and pharmaceutical compositions. In particular, the invention relates to a water-based pharmaceutical carrier. Advantageously, the carrier of the present invention allows the formulation of those active ingredients for which there is a need for these latter actives to adhere to the oropharyngeal and esophageal mucosae, in particular those active ingredients insoluble in aqueous media, for which there is a need for these latter actives to adhere to the oropharyngeal and esophageal mucosae. The present invention further relates to a pharmaceutical composition comprising said pharmaceutical carrier, said composition being particularly suitable for oral use.

Description

[0001] PHARMACEUTICAL CARRIER AND PHARMACEUTICAL COMPOSITION COMPRISING

[0002] THE SAME

[0003] FIELD OF THE INVENTION

[0004] The present invention relates to the technical field of pharmaceutical carriers or bases and pharmaceutical compositions.

[0005] In particular, the present invention relates to a water-based mucoadhesive pharmaceutical carrier suitable for oral administration. Advantageously, the pharmaceutical composition of the carrier of the present invention allows solubilizing those active ingredients which are poorly soluble in aqueous solutions, and increasing the residence time of the active ingredients carried by the latter at the level of the oropharyngeal and esophageal mucosa, increasing the bioavailability of the carried active ingredients. Moreover, the field of the invention covers all pharmaceutical compositions carrying the active ingredients, made with said mucoadhesive pharmaceutical carrier.

[0006] PRIOR ART

[0007] One of the greatest challenges that the pharmaceutical industries must face in the formulation of liquid pharmaceutical forms for oral use is related to problems of solubility of active ingredients or drugs belonging to classes II and IV of the Biopharmaceutical Classification System (BCS) and bioavailability of the carried drugs. Such problems are even more pronounced in the local treatment of pathological conditions of the oropharyngeal and esophageal mucosa, where the low residence time of the formulation limits the bioavailability of the drug and therefore the effectiveness of the treatment.

[0008] In particular, the active ingredient budesonide, used in the local treatment of eosinophilic esophagitis in children, is formulated extemporaneously as a viscous suspension at concentrations of 0.2 mg / mL. The limit of the current therapy is related to the low bioavailability of the active ingredient. In fact, the residence time of the formulation at the level of the esophageal mucosa is not sufficient for the drug, suspended in the carrier, to solubilize and spread in the mucosa, locally exerting its anti-inflammatory action.

[0009] There is therefore a need to overcome these problems.

[0010] BRIEF DESCRIPTION OF THE INVENTION

[0011] The Applicants have overcome the aforesaid problems by making mucoadhesive liquid preparations in which the active ingredient is completely solubilized. This makes it possible to advantageously increase the residence time of the drug at the mucosal level and bypass the dissolution process, thereby improving its bio availability and therefore its therapeutic efficacy.

[0012] In particular, the Applicants have now found a new pharmaceutical carrier and the related water-based pharmaceutical formulations. The composition of the carrier allows a rapid and complete solubilization of active pharmaceutical ingredients characterized by poor solubility in an aqueous environment, and by virtue of the mucoadhesive properties thereof, allows increasing the residence time of the related formulations thereof at the level of the oropharyngeal and esophageal mucosa. The composition of the pharmaceutical formulation made with the aforesaid carrier thus allows increasing the bioavailability of the carried active. In particular, the water-based pharmaceutical carrier allows formulating those active ingredients which are poorly soluble in aqueous media, in particular’ those having a specific solubility (hereinafter defined as % weight / volume) as defined in detail hereinafter.

[0013] Therefore, in a first aspect, the present invention relates to a water-based mucoadhesive pharmaceutical carrier according to claim 1.

[0014] Moreover, in a second aspect, the present invention relates to a pharmaceutical composition in liquid form for oral use according to claim 7.

[0015] Advantageously, the water-based pharmaceutical carrier allows obtaining liquid formulations in which active ingredients which are poorly soluble in aqueous environments are completely solubilized. Moreover, such formulations are advantageously characterized by increased bioavailability and chemical-physical stability of the carried active ingredient and optimal shelf-life of the pharmaceutical formulation.

[0016] Moreover, with reference to oral formulations and a need to adhere to the oropharyngeal and esophageal mucosae, a further advantage of the pharmaceutical carrier described in the present invention is that the composition thereof allows the pharmaceutical formulation to adhere to the oropharyngeal and esophageal mucosae, increasing the bioavailability of the carried drugs.

[0017] Moreover, the pharmaceutical carrier of the present invention advantageously allows an easy incorporation of the active ingredient (API), in other words it is manageable for those skilled in the art.

[0018] Other advantages, aspects, and embodiments of the present invention will be described hereinafter.

[0019] BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Fig. 1 shows the experimental results obtained regarding the chemical stability of budesonide in the pharmaceutical formulation.

[0021] Fig. 2 shows the experimental results obtained regarding the intrinsic solubility of budesonide in water and in the pharmaceutical carrier at 25°C.

[0022] Fig. 3 show's the experimental results obtained regarding the mucoadhesion profiles of the pharmaceutical carrier, the viscous control, and the non-viscous control.

[0023] Fig. 4 (A, B) shows the experimental results obtained regarding the rheological properties of the pharmaceutical carrier and the pharmaceutical formulation with budesonide.

[0024] DETAILED DESCRIPTION OF THE INVENTION

[0025] For the purposes of the invention, definitions of certain terms used in the present description and the appended claims are given below'. The term pharmaceutical carrier means a pharmaceutical base or pharmaceutical system, as commonly understood by those skilled in the art, which can be used to formulate an active ingredient. The terms "pharmaceutical carrier” or "water-based pharmaceutical carrier" are used interchangeably herein, when referring to the present invention.

[0026] Unless otherwise indicated, the percentages herein are percentages by weight / weight (w / w) with respect to the pharmaceutical carrier or pharmaceutical composition, respectively the subject of the paragraph of interest.

[0027] In accordance with a first aspect, the present invention thus relates to a water-based pharmaceutical carrier comprising:

[0028] - 2-40% w / w of a solubilizer selected from at least one cyclodextrin;

[0029] - 0.5-30% w / w of a humectant, said humectant being vegetable glycerol:

[0030] - 0.1-5% w / w of a visco sifter and mucoadhesive, said viscosifier and mucoadhesive being the polymer carboxymethylcellulose sodium (CMC Na);

[0031] ■ 0.1-5% w / w of a buffer system; and

[0032] - water as needed to 100% w / w for pharmaceutical use.

[0033] According to a preferred aspect, the pharmaceutical carrier of the invention and the pharmaceutical formulations thereof are characterized by a pH of 5.0-6.0.

[0034] With respect to the solubilizer, it is included in the pharmaceutical carrier of the invention preferably in a percentage of 10-25% w / w, more preferably in a percentage of 12-18% w / w.

[0035] With reference to the humectant, it is included in the pharmaceutical carrier of the invention preferably in a percentage of 1-15% w / w.

[0036] According to a preferred aspect, the at least one cyclodextrin is selected from the natural cyclodextrins alpha-, beta- and gamma- cyclodextrin and derivatives thereof, in which one or more hydroxyl groups thereof are substituted with carbon chains, for example, alkyl, hydroxy alkyl, carboxyalkyl, alkylcarbonyl, carbo xyalkyloxyalkyl, alk lcarbonylo alkyl, alkoxycarbonylalkyl, or hydroxy-(mono- or poly-alkoxy) alkyl groups; and in which each alkyl or alkylene moiety preferably contains up to six carbons. Moreover, these cyclodextrins can be obtained in various degrees of substitution, for example from 1 to 14, preferably from 4 to 7.

[0037] Here, the term "degree of substitution" means the approximate average number of substituent groups on a molecule or polymer. If the molecule is a cyclodextrin, for example hydroxypropyl-beta-cyclodextrin, the degree of substitution is the approximate number of hydroxypropyl groups. In the case of polymers, for example CMC Na, the degree of substitution is the approximate number of carboxymethyl groups, in the free and / or salified acid form. The substituted cyclodextrins which can be used in the invention include polyethers. Further examples of substituted cyclodextrins comprise ethers in which the hydrogen of one or more hydroxyl groups of the cyclodextrin is replaced by hydroxy-Ci -s-alkyl, carboxy-Ci-6-alkyl or Ci-6- alkyloxycai’bonyl-Ci-6-alkyl groups or mixed ethers thereof. In particular, such substituted cyclodextrins are ethers in which the hydrogen of one or more hydroxyl groups of the cyclodextrin is replaced by Ci-3-alkyl, hydroxy-C 2-4-alkyI or carboxyl-C 1.2-alkyl or, more in particular, by methyl, ethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, carboxymethyl or carboxyethyl. The term " Ci-g-alkyl" refers to saturated, linear and branched hydrocarbon radicals, with a number of carbon atoms between 1 and 6, such as methyl, ethyl, 1-methyl, 1,1 -dimethyl, propyl, 2- methylpropyl, butyl, pentyl, hexyl and the like. Preferably, other cyclodextrins contemplated for the present use include glucosyl- beta-cyclodextrin and malto syl- beta-cyclodextrin. Particularly useful for the present invention are randomly methylated beta-cyclodextrins and polyethers such as hydro xypropyl-beta-cyc lode xtrin, hydroxyethyl- beta-cyclodextrin, hydro xypropyl-gamma- cyclodextrin and hydroxyethyl-gamma-cyclodextrin, as well as sulfobutyl ethers, in particular the sulfobutyl ether of beta-cyclodextrin. In addition to simple cyclodextrins, branched cyclodextrins and cyclodextrin polymers can also be used.

[0038] According to a preferred aspect, the present invention includes mucoadhesive derivatives of the natural alpha, beta and gamma cyclodextrins in which one or more hydroxyl groups are substituted by chemical groups or carbon chains or carbon chains suitably functionalized with chemical groups having mucoadhesive properties. The term "chemical groups or carbon chains or carbon chains suitably functionalized with chemical groups having mucoadhesive properties" refers to those substituents of hydroxyl gro ups capable of establishing physical, primary chemical or secondary chemical bonds with the mucin present on the mucosae. In particular, physical bonds refers to the interpenetration between the carbon chains of mucoadhesive cyclodextrin and those of mucin, primary chemical bonds refers to covalent or ionic forces, resulting from chemical reactions between the functional groups of the carbon chain or cyclodextrin and mucin, secondary chemical bonds refers to electrostatic, hydrophobic, hydrogen bonds, and Van der Waals interactions which are established between the chemical groups of the carbon chain or cyclodextrin and mucin.

[0039] By way of non- limiting example, some chemical groups present on cyclodextrins or carbon chains linked to cyclodextrins can be free thiol groups (-SH) or protected by disulfide bridges (-S- S-R, where R - H, or linear or branched, saturated or unsaturated, and cyclic aromatic or aliphatic hydrocarbons), sulfur (-S') carboxyl (-COOH), carboxylated (-COO-), primary, secondary, and tertiary amines (-NR1R2, where Ri and R2 = H, or linear or branched, saturated or unsaturated, and cyclic aromatic or aliphatic hydrocarbons), ammonium (-[NRjReRs]* Ri, R.2 and R3 = H, or linear or branched, saturated or unsaturated, and cyclic aromatic or aliphatic hydrocarbons), sulfur (- SO4H), sulfate (-SO4 ), sulfone (-SO3H), sulfonate (-SO3') having mucosal properties.

[0040] By way of non- limiting example, in the present invention, the carbon chains can include mucoadhesive polymers such as PEG, chitosan, alginate or small molecules such as cysteine, N- acetylcysteine, homocysteine, or peptides such as glutathione.

[0041] Preferably in this invention, the derived cyclodextrins are selected from hydroxypropyl beta cyclodextrin, sulfobutylether beta-cyclodextrin, methyl beta-cyclodextrin or combinations thereof. More preferably, the cyclodextrin is 2-hydroxypropyl beta-cyclodextrin with a degree of substitution between 4 and 7. According to a preferred aspect, the buffer system is selected from a buffer system of citric acid, anhydrous trisodium citrate monohydrate, dihydrate or trihydrate.

[0042] By way of non-limiting example, the viscosifier and mucoadhesive is selected from acacia (gum Arabic), agar, magnesium aluminum silicate, sodium alginate, bentonite, carrageenan, polymers of Ceratonia Siliqua L., gelatin, gum Ghatti, guar gum, honey, corn starch, wheat starch, rice starch, potato starch, karaya gum, xanthan gum, tragacanth gum, cellulose and derivatives thereof, such as ethyl cellulose, ethyl hydroxyethyl cellulose, ethyl methyl cellulose, methylcellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl cellulose (CMC) (e.g., CMC Na, oxypolygelatin, pectin, polygeline, propylene carbonate, methyl vinyl ether / maleic anhydride copolymer (PVM / MA), poly(hydroxyethyl methacrylate), poly(methyl methoxy methacrylate), poly(ethyl methoxy methacrylate, a carbopol, a polymer of cross-linked acrylic acid (polyacrylate), a carbomer homopolymer or copolymer, a cross-linked functional carboxylic polymer, polyvinylpyrrolidone (PVP), a hydrophilic polysaccharide gum, one or more maltodextrins, alginic acid and salts thereof, hyaluronic acid and salts thereof, thiomers (e.g., a thiolated chitosan, thiolated polycarbophil, thiolated alginate, thiolated cellulose derivatives, thiolated carboxymethyl cellulose, thiolated polyacrylic acid or thiolated polyacrylates, thiolated hyaluronic acid), polyethylene glycols (e.g., PEG 200 ■■ 6000) and PEGylated polymers (e.g., PEGylated polyacrylic acid or PEGylated polyacrylate), a water-dispersible polycarboxylated vinyl polymer or mixtures thereof.

[0043] Preferably, the viscosifier and mucoadhesive is selected from CMC Na, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, methyl cellulose, tragacanth gum, xanthan gum, guar gum or mixtures thereof. More preferably, the viscosifier and mucoadhesive is CMC Na, having apparent viscosity of a 2% w / v solution, determined at 25°C, in a range between 350- 1000 mPa- s, degree of substitution in a range between 0.5 and 1 , preferably between 0.75 and 0.85, and % w / w sodium on the dry product in a range between 5 and 12. According to a preferred aspect, the pharmaceutical carrier further comprises at least one of the following:

[0044] - a preservative from 0.01 to 1% w / w,

[0045] ■■ a sweetener from 0.1 to 12% w / w,

[0046] - a flavor from 0.001 to 1% w / w.

[0047] According to a preferred aspect, the preservative is at least one selected from nipagin and nipasol.

[0048] According to a preferred aspect, the sweetener is selected from sucrose, sucralose, fructose, glucose, mannose, aspartame, erythritol, maltitol, sorbitol, mannitol, xylitol or a combination thereof.

[0049] According to a preferred aspect, the flavor is selected from raspberry, strawberry, cream, caramel, cocoa, vanilla flavor or a combination thereof.

[0050] According to a further aspect, the present invention thus relates to a pharmaceutical composition in liquid form for oral use comprising: one or more active ingredients having solubility in aqueous medium equal to or less than 0.5% w / v, said solubility referring to a temperature between 15 and 25°C, which must exert their action at the local level of the oropharyngeal and esophageal mucosae, or one or more active ingredients having solubility in aqueous medium greater than 0.5% w / v, said solubility referring to a temperature between 15 and 25°C, which must act locally at the level of the oropharyngeal and esophageal mucosae, or combinations thereof, and the aqueous-based pharmaceutical carrier as defined above.

[0051] Advantageously, the carrier of the invention is suitable for those active ingredients characterized by poor solubility in aqueous media and which have the need to adhere to the oropharyngeal and esophageal mucosae.

[0052] With reference to the pharmaceutical composition of the present invention, the active ingredient is preferably present at a level of 0.001 to 0.5% by weight / volume. According to a preferred aspect, the active ingredient is present from 0.001% w / v - 0.07% w / v (0.1 to 7 mg / 10 mL).

[0053] Again with reference to the pharmaceutical composition of the present invention, the active ingredient is preferably selected from budesonide, hydrocortisone acetate, hydrocortisone butyrate, ibuprofen, butyric acid, prednisolone, prednisone, triamcinolone, triamcinolone acetonide, clobetasol. Preferably, the active ingredient is budesonide.

[0054] .According to a preferred aspect, the pharmaceutical composition of the present invention is a composition for oral use.

[0055] The above description is to be understood by way of non-limiting example. Moreover, those skilled in the art will be able to understand that changes may be made without, departing from the scope of the present invention.

[0056] EXAMPLES

[0057] The following examples are intended to further illustrate certain embodiments of the present invention and therefore are not to be construed as limiting the latter. The water-based mucoadhesive pharmaceutical formulation was prepared as follows.

[0058] SET- UP ( incorporation of the active in the base)

[0059] Micronized Budesonide (7 mg) was solubilized at room temperature, by magnetic stirring, for a time of 30 minutes in the pharmaceutical carrier of the invention (10 mL), so as to promote the incorporation of the acti ve ingredient budesonide in the pharmaceutical carrier.

[0060] PACKAGING AND STORAGE

[0061] The water-based pharmaceutical composition thus obtained was packaged in 60-mL amber glass bottles and stored at temperatures of 4-8°C and 25 °C in the refrigerator and climatic chamber, respectively.

[0062] The pharmaceutical carrier of the invention was used as a basis for the formulation of a pharmaceutical composition as follows. Formulation

[0063] Budesonide 7 mg

[0064] Pharmaceutical carrier of the invention as needed to 10 mL

[0065] The set-up of the liquid pharmaceutical composition for oral use included solubilization at room temperature by magnetic stirring of budesonide (7 mg) and pharmaceutical carrier of the invention as needed to 10 ml,.

[0066] Packaging and storage

[0067] Package in amber glass bottles

[0068] Store at T = 4-8°C or 25°C

[0069] Comments of the parameters tested for the pharmaceutical formulation and pharmaceutical carrier of the aforesaid invention, as shown in Figures 1-4.

[0070] Intrinsic solubility of the active ingredient budesonide

[0071] As shown in Fig. 2, it is apparent that the pharmaceutical carrier is capable of considerably increasing the solubility of the active ingredient budesonide up to 0.7 mg / mL allowing therapeutic concentrations applicable for customized therapy to be reached. Such a measurement was carried out by incorporating the active in the water-based mucoadhesive pharmaceutical carrier in hand and in water (control). In particular, triplicate samples were prepared, in which an excess of active ingredient was added in the solvent (water-based mucoadhesive pharmaceutical carrier or water). Such samples were subjected to magnetic stirring for 72 hours (sufficient time to reach thermodynamic equilibrium) in a thermostat chamber at 25°C. After this period of time, aliquots of the samples were collected, centrifuged so as to separate the excess drug, and the supernatant, after being filtered with 0.45 p m diameter nylon filters, was analyzed by an appropriate method of high performance liquid chromatography (HPLC). Mucoadhesion profiles

[0072] As shown in Fig. 3, from the mucoadhesion profiles related to the pharmaceutical carrier of the invention, a viscous control (pharmaceutical carrier without solubilizing agent) and a non- viscous control (pharmaceutical carrier without mucoadhesive viscosifying agent), respectively, it is apparent that the presence of CMC Na provides the pharmaceutical carrier with a mucoadhesion power for more than 60 minutes.

[0073] In order to determine the mucoadhesive properties of the pharmaceutical carrier and the related formulation, in-vitro studies were carried out on pig esophagus. In three carriers, the pharmaceutical carrier of the invention, a viscous control (pharmaceutical carrier without solubilizing agent) and a non- viscous control (pharmaceutical carrier without mucoadhesive viscosifying agent), respectively, Fluorescein diacetate (FDA) was suspended at a concentration of 1 mg / mL. The three suspensions were applied to a portion of esophagus with a length-width size of 3x2 cm, positioned on a support inclined at 45° at room temperature (25 + 0.5 °C). 60 mL of phosphate buffer solution (PBS pH 6.8, 100 mM) was flowed over the mucosa at 1.0 mL / min and then collected in a glass beaker from which 0.5 mL volume aliquots were collected at different times. The samples were vigorously stirred for 30 s and incubated for 20 min at 37 °C in the presence of 0.5 mL of a 5M sodium hydroxide (NaOH) solution, in order to hydrolyze the FDA thus forming sodium fluorescein. Such samples were then centrifuged and an aliquot of the supernatant of each sample was analyzed using the Victor X3 spectrofluorometer (PerkinElmer, Waltham, MA, USA) for determining the fluorescence intensity. The mucoadhesive property (%) was calculated by quantification of residual FDA on the esophageal mucosa, by means of the following formula:

[0074] , / Fluorescence (sample) \

[0075] Mucoadhesion (%) = 100 — | ~~ - 7—: - - X 100 | luorescence t re erence )

[0076] Stability Profiles The chemical-physical stability profile of the active ingredient budesonide incorporated in the pharmaceutical carrier of the present invention was evaluated. In detail, extemporaneous formulations were made, having a concentration of 0.7 mg / mL, going to solubilize budesonide in the aforesaid pharmaceutical carrier. They were subjected to three different storage conditions: 4- 8 °C in a refrigerator, 25 °C in a thermostated chamber, and at 40°C with 70% relative humidity in a climatic chamber. The "in use” stability of the formulations and of the active was monitored for 120 days and periodic samples of the formulation were collected, which were analyzed by HPLC method in order to determine the residual titer of the active ingredient of the formulation over time and the possible appearance of drug degradants. Meanwhile, in order to monitor the physical stability, visual evaluations were carried out to observe the formation of solid precipitates inside the primary containers of the formulation and changes in color thereof. Moreover, periodic pH determinations were also carried out to assess whether the presence of the active could cause a substantial change in the pH of the pharmaceutical carrier and whether there was a tangible change in such a value over the storage period. The pharmaceutical composition was found to be chemically and physically stable when stored in the refrigerator (T = 4-8°C) or in a thermostated chamber (T - 25°C) for a period > 3 months (Fig. 1).

[0077] Rheological Properties

[0078] The rheological properties were studied by comparing the water-based mucoadhesive pharmaceutical carrier of the invention without the active ingredient budesonide and the pharmaceutical composition comprising the active. The study was carried out using a HAAKE™ M ARS iQ rheometer (ThermoFisher Scientific, Waltham, USA) provided with flat plate geometry (25 mm diameter and 500 pm plate spacing). The experiment was canned out at a temperature of 25 °C and each sample was conditioned at the same temperature for 5 minutes before analysis. The change in shear stress as a function of the change in shear rate was measured in a range between 0.1 and 100 s’1for the pharmaceutical carrier and the pharmaceutical formulation in the presence of budesonide at a concentration of 7 mg / 10 mL. The change in viscous modulus of the pharmaceutical carrier and the pharmaceutical formulation in the presence of budesonide at the concentration of 7 mg / 10 mL as a function of the change in angular speed in a range between 0.628 and 62.8 rad / s was evaluated. It is apparent how the incorporation of the active ingredient does not alter the rheological properties of the carrier (Fig. 4 A, B).

Claims

AMENDED CLAIMS received by the International Bureau on 18 April 2025 (18.04.2025)1. A water-based mucoadhesive pharmaceutical carrier comprising:- 2-40% w / w of a solubilizer selected from at least one cyclodextrin selected from natural alpha- , beta- and gamma- cyclodextrins and derivatives thereof, including 2-hydroxypropyl betacyclodextrin, sulfobutylether beta-cyclodextrin, methyl beta-cyclodextrin in various degrees of substitution, or combinations thereof and mucoadhesive cyclodextrines;- 0.5-30% w / w of a humectant, said humectant being vegetable glycerol;- 0.1-5% w / w of a buffer system,- 0.1-5% w / w of a viscosifier and mucoadhesive, said viscosifier and mucoadhesive being the polymer carboxymethylcellulose sodium (CMC Na) having a degree of substitution between 0.75 and 0.85, an apparent viscosity (2% w / v aqueous solution at 25°C) between 350 and 1000 mPa- s, and a sodium content of 5% to 12% by weight on the dry substance; andWater as needed to 100% w / w.

2. A pharmaceutical carrier according to any one of the preceding claims, wherein the at least one cyclodextrin is 2-hydroxypropyl beta-cyclodextrin in various degrees of substitution, preferably from 4 to 7.

3. A pharmaceutical carrier according to any one of the preceding claims, wherein the buffer system is selected from buffer system of citric acid, anhydrous trisodium citrate monohydrate, dihydrate or trihydrate.

4. A pharmaceutical carrier according to any one of the preceding claims, further comprising at least one of the following:- a preservative from 0.01 to 1% w / w,- a sweetener from 0.1 to 12% w / w,- a flavor from 0.001 to 1% w / w.

5. A pharmaceutical composition in liquid form for oral use comprising:one or more active ingredients and a water-based mucoadhesive pharmaceutical carrier according to any one of claims 1 to 4, said composition being suitable for local administration to the oropharyngeal and / or esophageal mucosae.

6. A pharmaceutical composition according to claim 5, wherein the active ingredient has a solubility equal to or less than 0.5% w / v, said solubility referring to a temperature between 15 and 25°C.

7. A pharmaceutical composition according to claim 6, wherein the active ingredient is present in a concentration within a range between 0.001% and 0.07% weight / volume.

8. A pharmaceutical composition according to claim 6 or 7, wherein the active ingredient is selected from budesonide, hydrocortisone acetate, hydrocortisone butyrate, ibuprofen, butyric acid, prednisolone, prednisone, triamcinolone, triamcinolone acetonide, clobetasol.