Oral composition, method for preparing an oral composition, use of an oral composition, kit and method for preventing or treating

Abstract

The present invention discloses a new oral spray composition of ondansetron hydrochloride, its method of preparation and use, kit and method of preventing or treating nausea and vomiting in cancer chemotherapy and in the postoperative period.

Description

ORAL COMPOSITION, METHOD FOR PREPARING AN ORAL COMPOSITION, USEOF AN ORAL COMPOSITION, KIT AND METHOD FOR PREVENTING OR TREATINGFIELD OF THE INVENTION

[0001] The present invention belongs to the pharmaceutical field and relates to an oral spray composition of ondansetron hydrochloride, its method of preparation and use, kit and method of prevention or treatment of nausea and vomiting, including when resulting from cancer chemotherapy treatment or the postoperative period .BACKGROUND OF INVENTION

[0002] Ondansetron is a competitive 5-HTs serotonin receptor antagonist used to prevent nausea and vomiting, including when resulting from cancer chemotherapy treatment or in the postoperative period, and has reported anxiolytic and neuroleptic properties, preferably being used in the form of ondansetron hydrochloride .

[0003] Having been developed in the 1980s and approved by the federal agency of the US Department of Health and Human Services (Food and Drug Administration, FDA) since January 1991, ondansetron has demonstrated a long history of use and efficacy. Commonly formulated as oral tablets, orally disintegrating tablets (ODT) and injections, also available as generic products, ondansetron continues to see contemporary innovations in its formulation and use, including the development of soluble films for oral use that are discreet in administration and less unpleasant for use by patients who try to swallow tablets during emesis .

[0004] Despite being available by injection, ondansetron is commonly administered orally, especially the ODT form due to its low solubility in water, namely 0.248 mg / mL at 25 °C.

[0005] In this regard, it is worth noting that ondansetron, even at low dosages, has a strong and unpleasant bitter taste and this is the main problem when administering the drug orally. The product in coated tablet form manages to inhibit the strong taste, but when making the product available in granule and / or solution form, the time parameter of maximum plasma concentration should be reduced.

[0006] In addition, the use of excipients to mask the bitter and unpleasant taste can impair the solubility of ondansetron due to the salting out effect.

[0007] Thus, obtaining a product with a pleasant taste, with an adequate concentration in solution for widespread and practical use are the main issues to be overcome. There is also the issue of solubility, where concentrated solutions of ondansetron are not feasible in aqueous media and obtaining a system of cosolvents and additives at a suitable pH becomes necessary.

[0008] At the time of this disclosure, there is no composition of ondansetron hydrochloride, the formulation of which has been developed to promote the rapid availability of the drug in the form of a solution, in high concentration to be used as an oral spray in low volumes, acceptable and masking taste.

[0009] There is therefore a pressing need to develop a pharmaceutical composition of ondansetron hydrochloride in solution form that has good administration and dosage characteristics, as well as good stability and solubility, and which also favors adherence to treatment.

[0010] Document W02016 / 052960 describes an orally disintegrating film composition comprising ondansetron, magnesium oxide or magnesium hydroxide and a film-forming agent, an orally disintegrating film made thereof and a method for preparing the orally disintegrating film.

[0011] However, this document does not deal with an oral spray formulation, nor does it address the technical problem of ondansetron's low solubility.

[0012] For its part, document WO 2007 / 123955 generically discloses stable formulations of an active pharmaceutical agent suitable for administration by oral spray for absorption through the oral mucosa and related methods of preparation and administration of formulations of active pharmaceutical agents. In particular, the document specifies ondansetron as a possible active ingredient in the formulations.

[0013] Although the formulations disclosed in this document comprise agents to mask the bitter taste of ondansetron, this document does not address the technical problem of the solubility of ondansetron, which can be impaired by masking agents and other excipients (the salting out effect) .

[0014] In fact, none of the cited documents addresses the issue of ondansetron's solubility related to the use of masking agents in an oral spray pharmaceutical composition.

[0015] In this sense, there are several challenges related to the development of ondansetron hydrochloride formulations, such as its stability and solubility. Specifically, it is known that active pharmaceutical ingredients in liquid form are more susceptible to physical and chemical instability than in solid form.

[0016] Thus, for oral solutions, the active pharmaceutical ingredient needs to be chemically and physically stable. Specifically, trace amounts of impurities of active pharmaceutical ingredients or excipients and the pH of the solution can cause degradation of the active pharmaceutical ingredient, increasing the instability of the solution.

[0017] In this context, it is advantageous to develop new alternatives of ondansetron hydrochloride composition that can be more easily administered, in the form of a solution with high concentration and solubility, providing good shelf life characteristics .

[0018] Therefore, the present invention relates to a new and inventive pharmaceutical composition of ondansetron hydrochloride to be used as an oral spray in low volumes, acceptable and masking taste, enabling adherence to treatment, and which has adequate pharmacological action, as well as high stability and solubility, even when the ondansetron hydrochloride is in high concentration in the composition.SUMMARY OF THE INVENTION

[0019] The present invention discloses a new ondansetron hydrochloride oral spray composition, its method of preparation, its use, kit and method of preventing or treating nausea and vomiting, including when resulting from cancer chemotherapy treatment or in the post-operative period.

[0020] A first embodiment of the invention relates to an oral spray composition of ondansetron hydrochloride, associated with pharmaceutically acceptable excipients and vehicles.

[0021] In a second embodiment of the invention, a method of preparing said oral spray composition is described.

[0022] A third embodiment discloses the use of said liquid composition to prepare a medicament to prevent or treat nausea and vomiting.

[0023] A fourth preferred embodiment of the invention relates to a method for preventing or treating nausea and vomiting.

[0024] And yet, an additional embodiment of the invention relates to a kit comprising the liquid oral spray composition of ondansetron hydrochloride associated with a release device in a package with actuator coupled to a prolonger and, optionally, administration instructions.

[0025] Surprisingly, the inventors of the present application have developed a pharmaceutical composition of ondansetron hydrochloride, in the form of a solution with high concentration, acceptable and masking taste, which has maintained its pharmacological action when compared to existing ondansetron compositions in the prior art, while providing greater patient comfort and adherence to treatment, as well as precise control of the dosage and solubility of the composition, without the adverse effects of instability resulting from the use of masking agents and other excipients through the salting out effect.BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 shows the flowchart illustrating the preparation process of the ondansetron hydrochloride oral spray pharmaceutical composition of the present invention.DETAILED DESCRIPTION OF THE INVENTION

[0027] The terms "ondansetron hydrochloride oral spray composition", "oral spray liquid composition" "pharmaceutical composition", "oral spray composition" and "ondansetron hydrochloride composition" are interchangeable and should beunderstood as the composition of the present invention comprising ondansetron hydrochloride associated with pharmaceutically acceptable excipients and vehicles.

[0028] In turn, the term "pharmaceutically acceptable excipient" is defined as any substance other than the active pharmaceutical ingredient, which has been evaluated for its safety and / or is approved for pharmaceutical use by a competent regulatory authority, if applicable.

[0029] The present invention relates to an ondansetron hydrochloride product, the formulation of which has been developed in such a way as to promote rapid dissolution of the drug in the form of a solution with a high concentration of the same, with an acceptable and masking taste, to be used as an oral spray in low volumes.

[0030] As indicated here, the prior art already contains ondansetron hydrochloride compositions. However, it fails to address the technical problem of ondansetron's solubility, which can be further impaired by masking agents and other excipients (the salting out effect) .

[0031] In particular, the inventors of the present invention have unexpectedly been able to obtain a new pharmaceutical composition with a high concentration of ondansetron hydrochloride that maintains good solubility and stability characteristics of the active ingredient during and after the process of preparing the composition, even with the use of masking agents and other excipients.

[0032] When compared to the pharmaceutical composition with a low concentration of ondansetron hydrochloride, the oral spray composition of the present invention has the advantage of offering greater ease of use, through the administration andingestion of a small volume dose, with an acceptable and masking taste, with a rapid and long-lasting effect.

[0033] Consequently, the liquid pharmaceutical composition of oral spray provides greater comfort and adherence to patients in the prevention and treatment of nausea and vomiting, including when caused by cytotoxic chemotherapy drugs, such as cisplatin, and has anxiolytic and neuroleptic properties.

[0034] The composition has a high concentration of the active ingredient which allows it to be administered in a very small volume. The small volume is sufficient to be accommodated in a small bottle with a hinged mobile applicator, so it is portable and can be self-administered without the need for other liquids or professional assistance.

[0035] In a first embodiment, the composition of the present invention comprises ondansetron hydrochloride, associated with pharmaceutically acceptable excipients and vehicles. Preferably, the composition of the present invention is in the form of a solution to be used as an oral spray.

[0036] These excipients are selected according to the pharmaceutical dosage form of interest, its route of administration, physicochemical compatibility with the active ingredient and the effect on efficacy. For example, pharmaceutically acceptable excipients can be selected from ROWE, R.C. et al. "Handbook of Pharmaceutical Excipients", 6thed. USA, 2009, the Brazilian Pharmacopoeia or a foreign counterpart, such as the American Pharmacopoeia or the European Pharmacopoeia.

[0037] According to the present invention, the one or more pharmaceutically acceptable excipients can be selected from the group consisting of preservatives, sweeteners, thickeners, stabilizers flavorings antioxidants crystallizationinhibitors, chelating agents, buffering agents, acidulants, alkanilizers, solvents, co-solvents, supersolvents, solubilizers, vehicles and combinations thereof, whereby the same excipient can have more than one function in the composition. In some embodiments of the invention, the composition comprises as excipients solvents, co-solvents, supersolvents, crystallization inhibitors, sweeteners, flavorings, preservatives, vehicles and combinations thereof.

[0038] According to the present invention, water is used as the main solvent and it is necessary to use a co-solvent that can increase the soluble fraction of ondansetron, so that it is possible to achieve the final composition with a high concentration of ondansetron.

[0039] The co-solvent may be selected from the group consisting of mono-, di-, or trihydroxylated alcohols, pharmaceutically acceptable solvents, and combinations thereof. In preferred embodiments, the co-solvent is selected from the group consisting of glycerin, propylene glycol, polyethylene glycol 400 and sorbitol. Preferably, the co-solvent is glycerin.

[0040] According to the present invention, the vehicle can be selected from the group consisting of purified water, esters in general, mineral oils, vegetable oils and mixtures thereof . In preferred embodiments, the vehicle is purified water.

[0041] The co-solvent can be present in the composition in a system in a ratio from 1:1 to 1: 10 with purified water. Optionally, a supersolvent and / or an inhibitor can be used in combination .

[0042] The viscosity of the ondansetron hydrochloride composition cannot be high, as the composition needs to beatomized in the form of an oral spray. Preferably, the viscosity of the composition is less than 500 cP.

[0043] According to the present invention, the pH of the composition is in the range from 3.0 to 4.5, preferably in the range from 3.5 to 4.0, without the need to add a buffering material such as a pH adjusting agent.

[0044] Optionally, the oral spray composition further comprises as excipients ethyl alcohol as a supersolvent and / or povidone K30 as a crystallization inhibitor, in order to maintain the stability of the composition and avoid precipitation due to the salting out effect after the addition of other solutes to the composition, for example sweeteners and preservatives.

[0045] According to the present invention, the sweetener can be selected from the group consisting of natural or synthetic sweeteners, and combinations thereof, which confer a sweet taste to the composition. In preferred embodiments, the sweetener is selected from the group consisting of dihydrochalcone neoesperidin, steviol glycosides, mannitol, sorbitol, sucralose, thaumatin, xylitol, neotame, and combinations thereof.

[0046] In even more preferred embodiments, a combination of sucralose, neotame and thaumatin are used as sweeteners in the composition. The combination of sucralose and neotame in the composition has an additive synergistic effect, reducing the amount of sweeteners needed to achieve greater sweetness. Other sweeteners would need much higher concentrations to achieve the desired masking, which could interfere with the ionic salt balance and lead to precipitation of the drug.

[0047] The use of thaumatin in this combination is intended to prolong the sweetening effect as much as possible, reducing the bitter taste of ondansetron and optimizing its palatability .

[0048] According to the present invention, the flavoring agent can be selected from the group consisting of any agents with the ability to mask unpleasant flavors present in the composition, including natural and artificial flavoring agents.

[0049] In preferred embodiments, the flavoring is mandarin mint aroma comprising mandarin aroma, menthol and eucalyptol.

[0050] Specifically, menthol and eucalyptol act to "anaesthetize" the response to the bitter taste and reduce the unpleasant bitter sensation of ondansetron.

[0051] According to the present invention, the oral spray composition further comprises sodium benzoate as a preservative with the function of inhibiting the growth of microorganisms such as bacteria, fungi and yeasts that could compromise the effectiveness of the oral spray composition.

[0052] During the development of the new composition, the solubilization and stabilization of ondansetron hydrochloride proved challenging in combination with the issue of masking the bitter taste of ondansetron.

[0053] The inventors therefore prepared various combinations in order to identify optimized concentration ranges for the components of the composition, namely ondansetron hydrochloride associated with one or more excipients and vehicles.

[0054] In some embodiments of the invention, the concentration of ondansetron hydrochloride in the composition can vary from 15 to 35 mg / mL, preferably from 20 to 30 mg / mL, more preferably, the concentration of ondansetron hydrochloride in the composition is 25 mg / mL.

[0055] According to the present invention, glycerin can be present in the composition at a concentration in the range from 350 to 450 mg / mL, preferably a concentration of 400 mg / mL.

[0056] In some embodiments of the invention, the total concentration of ethyl alcohol as a supersolvent in the composition can vary in the range of 50 to 150 mg / mL. In preferred embodiments, the total concentration of ethyl alcohol is 100 mg / mL of the composition.

[0057] In some embodiments of the invention, the total concentration of povidone K30 as a crystallization inhibitor in the composition can vary in the range from 30 to 70 mg / mL, preferably in the range from 40 to 60 mg / mL. In even more preferred embodiments, the total concentration of povidone K30 in the composition is 50 mg / mL.

[0058] In one embodiment of the invention, the total concentration of sodium benzoate as a preservative in the composition can vary in the range from 0.10 to 0.40 mg / mL of the composition. In preferred embodiments, the final concentration of sodium benzoate in the composition is 0.20 mg / ml of the composition .

[0059] According to the present invention, sucralose can be present in a concentration from 15 to 25 mg / mL, preferably 20 mg / mL, while neotame can be present in a concentration from 3 to 7 mg / mL, preferably 5 mg / mL and thaumatin can be present in a concentration from 0.5 to 1.5 mg / mL, preferably 1.0 mg / mL.

[0060] In some embodiments, the oral spray composition may comprise mandarin at a concentration of 5 to 15 mg / mL, preferably 10 mg / mL.

[0061] In some embodiments of the invention, the final concentration of water in the oral spray composition can vary inthe range of 30 to 50% w / w based on the total weight of the composition. In preferred embodiments, the concentration of water in the composition can vary from 35 to 45% w / w based on the total weight of the composition. In additionally preferred embodiments, the concentration of water in the composition is 38.88% w / w based on the total weight of the composition.

[0062] As mentioned above, at the time of the present disclosure, no pharmaceutical composition of ondansetron hydrochloride combining the concentrations of ingredients and the form of administration disclosed herein had been taught or even suggested .

[0063] In a second embodiment, the process for producing the oral spray pharmaceutical composition of the present invention involves different steps that are decisive for obtaining the product in a stable form.

[0064] The ondansetron hydrochloride composition of the present invention can be prepared by a process comprising the following steps: a) adding water, ethyl alcohol, and povidone K30 to a suitable main container; b) stirring until total solubilization at room temperature; c) adding sodium benzoate; d) stirring until total solubilization; e) adding sucralose; f) stirring until total solubilization; g) in an additional container, adding glycerin and water; h) stirring until completely homogenized, followed by heating; i) adding ondansetron hydrochloride;j ) shaking until total homogenization; k) maintaining under mild stirring and heating for a period of time; l) cooling; m) transferring to the main container under stirring; n) maintaining under stirring and adding neotame; o) maintaining under stirring and temperature, followed by stirring until total solubilization; p) adding thaumatin; q) maintaining under stirring and temperature, followed by stirring until total solubilization; r) cooling under stirring; s) adding mandarin; t) diluting with purified water; and u) stirring for a sufficient period of time.

[0065] Optionally, the solution resulting from step u) may go through a primary packaging / f illing step in a filling machine, followed by a volume by weight check and a bottle closure check.

[0066] In preferred embodiments, the temperature of step b) is in the range of 15 to 30°C, while the heating temperature of steps h) and k) is in the range of 80 to 85°C. The heating of step k) is carried out for a period of time in the range of 25 to 40 minutes, preferably 30 minutes.

[0067] The cooling of step 1) is performed until a temperature in the range from 50 to 60°C, preferably in the range from 55 to 60°C.

[0068] The temperature of steps o) and q) is in the range from 45 to 50°C and the cooling of step r) is performed until atemperature of 30°C. In addition, stirring in step u) takes place for a period of time in the range of 5 to 15 minutes, preferably for 10 minutes .

[0069] Considering that the product needs to be atomized for application as an oral spray, the viscosity of the composition should not be high (< 500 cp) .

[0070] Specifically, the application of heating in the solubilization step of ondansetron hydrochloride is critical as it helps to completely eliminate microscopic crystals that could be precursors to recrystallization.

[0071] This step is carried out under more severe heating conditions, i.e. between 80 and 85 °C, because the volume used is lower than the system obtained at the end of the process.

[0072] In addition, the heating period for the solubilization step of the ondansetron hydrochloride can vary from 27 to 43 minutes, preferably 30 minutes.

[0073] A prolonged heating period of more than 45 minutes would lead to the onset of degradation of the drug and also of the glycerin, which becomes more yellowish. In addition, a heating period of less than 25 minutes would result in the presence of residual crystals in the medium.

[0074] As described above, the combination of sucralose and neotame as sweeteners has an additive effect, reducing the amount needed to achieve greater sweetness. Other sweeteners would need much higher concentrations to achieve the desired masking, which could interfere with the ionic salt balance and lead to precipitation of ondansetron hydrochloride.

[0075] One of the criteria for selecting the flavoring for the oral spray composition was to use mandarin mint flavoring sothat, in addition to the sweeteners, it could act as a masking effect .

[0076] Obtaining a product with an optimized masking effect was based on several fronts, such as sweeteners with an enhanced additive effect (sucralose and neotame) , sweeteners with a prolonged effect (thaumatin) and materials to reduce the bitter effect on the taste buds on an individual's tongue.

[0077] In a further embodiment, the present invention features the use of the oral spray composition of ondansetron hydrochloride to prepare a medicament for preventing or treating nausea and vomiting, including when resulting from cancer chemotherapy treatment or in the post-operative period of a patient in need thereof .

[0078] In yet another embodiment, the present invention presents a method for preventing nausea and vomiting, including when resulting from cancer chemotherapy treatment or in the postoperative period by administering a therapeutically effective amount of the oral spray composition of ondansetron hydrochloride to a patient in need thereof .

[0079] In another embodiment, the present invention presents a kit comprising the composition of ondansetron hydrochloride disclosed herein. The kit according to the present invention may comprise such composition associated with any suitable release device, for example in a package with actuator coupled with a prolonger aimed at the least possible contact with the oral mucosa and, optionally, administration instructions.

[0080] In this sense, the packaging, in this case the actuator with extended applicator, is another factor to optimize the masking effect of the bitter taste of ondansetron, reducing the spread of the product in the oral cavity.EXAMPLES

[0081] The following examples, described in detail, serve to illustrate embodiments of the present invention, without, however, limiting its scope of protection.Example 1 - Production process for an ondansetron hydrochloride oral spray composition

[0082] The following is a process for preparing an oral spray composition of ondansetron hydrochloride, as illustrated in the flowchart in figure 1:

[0083] In a suitable main container, water, ethyl alcohol and povidone K30 are added under stirring until total solubilization, at an ambient temperature of between 15-30°C.

[0084] Next, sodium benzoate and sucralose are added individually, with stirring until each of the respective ingredients is completely solubilized.

[0085] In an additional container, glycerin and water are added under stirring and heating at a temperature between 80-85°C until completely homogenized. Next, ondansetron hydrochloride is added to the resulting product, stirred until completely homogenized and kept under mild stirring for 30 minutes at a temperature between 80-85°C.

[0086] This is followed by a cooling step to a temperature of between 55-60°C and the resulting product is transferred to the main container under agitation, and agitation is maintained with the subsequent individual addition of neotame and thaumatin at a temperature of 45-50°C, until each ingredient is completely solubilized .

[0087] This is followed by a cooling step under stirring to 30°C, with the subsequent addition of mandarin (mint aroma) ,volume adjustment with purified water and stirring for 10 minutes .

[0088] The resulting solution then goes through a primary packaging / filling step in a filling machine.

[0089] Finally, the volume by weight is checked and the bottles are sealed.Example 2 - Exemplary oral spray composition

[0090] The following is an exemplary oral spray composition of ondansetron hydrochloride prepared in accordance with the present invention. Table 1 shows each of the ingredients, their respective concentrations, percentages and functions in the exemplary composition.Table 1 : Exemplary oral spray compositionin which the mandarin mint aroma is composed of:

[0091] The density of the exemplary oral spray composition is 1.14 g / mL .Example 3 - Results of the Stability Test

[0092] The formulation was evaluated for stability in polyethylene packaging using a 200 pL aluminum dosimeter valve with an actuator and extension. This product delivers a dose of 4 mg of ondansetron in each actuation.

[0093] After finalizing the development of the 25 mg / mL oral spray pharmaceutical composition of ondansetron hydrochloride, according to Example 2, a pilot batch named GSG033 / 23 was handled. Samples from the pilot batch were subjected to a stability study under different storage conditions (e.g. container material, temperature and time) .

[0094] The stability data are shown in Table 2 below and indicate satisfactory results for the stability of the oral spray composition, with storage in glass vials and plastic bottles, under the conditions 40°C / 30 days and 50°C / 30 days) .Table 2: Stability test data

[0095] It is understood that where a parameter range is provided, all integers and ranges within that range, and tenths and hundredths thereof, are also provided by the embodiments. For example, "5-10%" includes 5%, 6%, 7%, 8%, 9%, and 10%; 5.0%, 5.1%, 5.2%. .. .9.8%, 9.9%, and 10.0%; and 5.00%, 5.01%, 5.02 % . . . .9.98 % , 9.99%, and 10.00%, as well as, for example, 6-9%, 5.1%-9.9%, and 5.01%-9.99%. Similarly, where a list is presented, unless stated otherwise, it is to be understood that each individual element of that list, and every combination of components of that list, is a separate embodiment. For example, "1, 2, 3, 4, and 5" encompasses, among numerous embodiments, 1; 2; 3; 1 and 2; 3 and 5; 1, 3, and 5; and 1, 2, 4, and 5.

[0096] It should be understood that the embodiments described above are merely illustrative and that various modifications can be made to them by a person skilled in the art without departing from the scope of the present invention. Consequently, the present invention should not be considered limited to the exemplary embodiments described in the present application. In addition, the present disclosure may include subject matter not currently claimed, but which may be claimed in the future in combination with or separately from the features now claimed.

Claims

CLAIMS1. An oral spray composition comprising ondansetron hydrochloride at a concentration from 15 to 35 mg / mL, in association with pharmaceutically acceptable excipients and vehicles .

2. The oral spray composition according to claim 1, wherein the ondansetron hydrochloride is present in a concentration from 20 to 30 mg / mL, preferably a concentration of 25 mg / mL.

3. The oral spray composition according to claim 1 or 2, wherein the pharmaceutically acceptable excipients are selected from the group consisting of preservatives, sweeteners, thickeners, stabilizers, flavorings, antioxidants, crystallization inhibitors, chelators, buffers, acidulants, alkanilizers, solvents, co-solvents, supersolvents, solubilizers, vehicles and combinations thereof .

4. The oral spray composition according to any one of claims 1 to 3, comprising water in an amount in the range of 30 to 50% w / w based on the total weight of the composition, preferably, an amount in the range of 35 to 45% w / w based on the total weight of the composition, more preferably, an amount of 38.88% w / w based on the total weight of the composition.

5. The oral spray composition according to any one of claims 1 to 4, further comprising glycerin in a concentration in the range from 350 to 450 mg / mL, preferably a concentration of 400 mg / mL.

6. The oral spray composition according to any one of claims 1 to 5, further comprising povidone K30 in a concentration from 30 to 70 mg / mL, preferably, a concentration from 40 to 60 mg / mL, more preferably, a concentration of 50 mg / mL.

7. The oral spray composition according to any one of claims 1 to 6, further comprising a combination of sucralose, neotame and thaumatin as sweeteners .

8. The oral spray composition according to claim 7, wherein the sucralose is present in a concentration from 15 to 25 mg / mL, preferably 20 mg / mL.

9. The oral spray composition according to claim 7, wherein the neotame is present in a concentration from 3 to 7 mg / mL, preferably 5 mg / mL.

10. The oral spray composition according to claim 7, wherein the thaumatin is present in a concentration from 0.5 to 1.5 mg / mL, preferably 1.0 mg / mL.

11. The oral spray composition according to any one of claims 1 to 10, further comprising mandarin aroma as a flavoring.

12. The oral spray composition according to claim 11, wherein the mandarin is present in a concentration from 5 to 15 mg / mL, preferably 10 mg / mL.

13. The oral spray composition according to any one of claims 1 to 12, being in the form of a solution.

14. A process for producing an oral spray composition of ondansetron hydrochloride as defined in any one of claims 1 to 13, comprising the following steps: a) adding water, ethyl alcohol, and povidone K30 to a suitable main container; b) stirring until total solubilization at room temperature; c) adding sodium benzoate; d) stirring until total solubilization; e) adding sucralose; f) stirring until total solubilization;g) in an additional container, adding glycerin and water; h) stirring until completely homogenized, followed by heating; i) adding ondansetron hydrochloride; j ) shaking until total homogenization; k) maintaining under mild stirring and heating for a period of time; l) cooling; m) transferring to the main container under stirring; n) maintaining under stirring and adding neotame; o) maintaining under stirring and temperature, followed by stirring until total solubilization; p) adding thaumatin; q) maintaining under stirring and temperature, followed by stirring until total solubilization; r) cooling under stirring; s) adding mandarin; t) diluting with purified water; and u) stirring for a sufficient period of time.

15. The process according to claim 14, wherein: i) the temperature of step b) is in the range from 15 to 30°C; and / or ii) the heating temperature of steps h) and k) is in the range from 80 to 85 °C; and / or iii) the heating of step k) is carried out for a period of time in the range from 25 to 40 minutes, preferably 30 minutes; and / or iv) the cooling of step 1) is performed until a temperature in the range from 50 to 60 °C, preferably in the range of 55 to 60 °C; and / orv) the temperature of steps o) and q) is in the range from 45 to 50 °C; and / or vi ) the cooling of step r) is carried out until a temperature of 30 °C; and / or vii) the stirring of step u) is carried out for a period of time in the range from 5 to 15 minutes, preferably for 10 minutes .

16. A use of the composition as defined in any one of claims 1 to 13, for the preparation of a medicament for preventing or treating nausea and vomiting in a patient in need thereof.

17. A method for preventing or treating nausea and vomiting comprising administering to a patient in need thereof a therapeutically effective amount of the composition as defined in any one of claims 1 to 13.

18. A kit comprising the composition as defined in any one of claims 1 to 13, a release device and, optionally, administration instructions .

19. The kit according to claim 18, wherein the release device is in the form of a package with an actuator coupled to a prolonger.

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