FR3047663A1 - DISPERSIBLE TABLET - Google Patents

Abstract

The invention relates to a dispersible tablet, characterized in that it comprises an active phase representing at least 30% by weight of the total mass of the tablet, and an excipient phase representing at most 70% by weight of the total mass of the tablet, said active phase comprising at least in combination with paracetamol and vitamin C; said excipient phase comprising at least one disintegrant.

Description

DISPERSIBLE TABLET

The present invention relates to a medicament for the treatment of influenza, colds, rhinitis or rhinopharyngitis.

In some cases, the complexity of the physiological mechanisms causing a pathology requires the prescription of several active substances. In this case, the combination of these substances, at fixed doses, in one and the same galenic formulation can, while improving its safety and its compliance, provide a possible synergistic effect between the active principles for the treatment of the pathology. Such forms also improve the comfort of the patient.

The observance of the treatment is defined as strict compliance with the medical prescription, both in dosage and duration.

The invention relates more particularly to combinations of active principles comprising both paracetamol (or acetaminophen), vitamin C (or ascorbic acid) and optionally a third active ingredient.

There are currently available formulations on the market comprising a combination of paracetamol, vitamin C and possibly another active ingredient: pheniramine.

Examples include the following pharmaceutical specialties: - FERVEX® STATE GRIPPAL PARACETAMOL / VITAMIN C / PHENIRAMINE ADULTS; - FERVEX® STATE GRIPPAL PARACETAMOL / VITAMIN C / PHENIRAMINE ADULTS SUGAR-FREE; - DOLI® GRIPPAL CONDITION PARACETAMOL / VITAMIN C / PHENIRAMINE; - HUMEX® LIB STATUS GRIPPAL PARACETAMOL / VITAMIN C / PHENIRAMINE; - PARACETAMOL / VITAMIN C / PHENIRAMINE MYLAN CONSEIL®; or else - PARACETAMOL / VITAMIN C / PHENIRAMINE SANDOZ CONSEIL®.

These formulations are either granules for FERVEX® formulations or powders for oral solution with respect to the other formulations mentioned.

The formulations in the form of a mixture of powders have many drawbacks and in particular in terms of homogeneity between the various active ingredients and excipients, for example sweeteners, etc. Moreover, stability problems can arise especially in the presence of several active ingredients.

The granules may solve some of these problems but are an obsolete form impractical and often unstable.

There is also the pharmaceutical specialty FERVEX RHUME DAY AND NIGHT®, wherein the tablet "day" comprises the three aforementioned assets. This tablet is a film-coated tablet.

The form, film-coated tablet, has many disadvantages, including the requirement for the patient to swallow the tablet. In addition, the bioavailability is less good and less rapid than with a dispersible tablet.

The presence of these obsolete pharmaceutical forms on the market is explained by the technical difficulty of the preparation of forms, dispersible tablets.

Thus, it would seem that there are particular difficulties in formulating such active principles in the form of dispersible tablet, which is however the most suitable form for drugs often marketed without prescription for which the patient will seek a true comfort in use.

These difficulties have been identified in the prior art, and various solutions have been made.

In the application FR 2 187 312 in the name of BLUM, is disclosed a tablet comprising paracetamol, ascorbic acid and chlorphenamine. The tablet is an effervescent tablet and the active phase represents about 17% of the total mass of the tablet.

WO 2007/113536 in the name of RECKITT BENCKISER HEALTHCARE LTD. relates to dispersible tablets comprising paracetamol and an encapsulated flavor. The manufacture of a tablet comprising paracetamol is described as being difficult and preferably carried out by wet granulation, said wet granulation making it difficult to incorporate aromas that are necessary to mask the taste of paracetamol. A trial of manufacture of aroma-free tablets with directly compressible paracetamol which is coated with pregelatinized starch and phenylephrine hydrochloride by direct compression is described but only disintegration has been verified. The proposed solution for preparing a flavored tablet is the addition of an encapsulated flavoring agent, which, according to the applicant, makes it possible to manufacture a satisfactory dispersible tablet by direct compression comprising an active phase representing up to 60% of the total mass of the tablet.

In the application WO 01/19336 in the name of CLL PHARMA, is disclosed an orodispersible formulation comprising paracetamol and at least one weakly compressible diluent which is sucrose obtained by direct compression. In the examples, the active phase represents less than 35% of the total mass of the tablet.

In the context of the present application, the term "dispersible tablet" a tablet being capable of disintegrating in solution in water which will be qualified as "water-dispersible tablet" or being capable of disintegrating in the mouth of a patient who will be qualified as an orodispersible tablet.

In terms of disintegration rate, the European Pharmacopoeia (version 8.0) defines a "dispersible tablet" as being a tablet capable of dispersing in purified water at room temperature in less than 3 minutes.

The problem to be solved is thus to formulate in the form of dispersible tablets, combinations of active ingredients comprising both paracetamol (or acetaminophen), vitamin C (or ascorbic acid) and optionally a third active ingredient .

The active ingredients to be formulated are described below.

Paracetamol (or acetaminophen) (CAS 103-90-2) is the common name of a widely used active ingredient, used in the composition of many pharmaceutical specialties (eg DOLIPRANE®, EFFERALGAN®). Paracetamol is an active ingredient widely used for over-the-counter products, it is an analgesic and an antipyretic, also used to relieve pain and headaches, it is an important active ingredient for many indications (eg colds , flu). Its toxicity is to be taken into account in the formulation. The maximum daily dose is 3 g and the recommended daily doses (in adults) are between 500 and 1000 mg.

In the context of the present application is meant paracetamol, paracetamol, its derivatives, and its various crystalline forms, its salts (eg paracetamol hydrochloride) and mixtures thereof.

[00024] Vitamin C (or ascorbic acid) (CAS 50-81-7) is an active ingredient widely used in self-medication in common colds. It has a protective effect on the incidence of colds, so that it can be advantageously associated with another active substance in flu remedies. In France the recommended daily dose (in adults) is about 110 mg.

In the context of the present application is meant by vitamin C (or ascorbic acid) ascorbic acid and its salts. In one embodiment, the salt is selected from the group consisting of sodium ascorbate, calcium ascorbate, and potassium ascorbate, as well as mixtures thereof.

Pheniramine is a sedative antihistamine active ingredient often combined with an analgesic to prevent sneezing, itching or watery eyes and nose, as well as other symptoms of allergy or colds. The recommended daily dose (in adults) is about 24 mg.

In the context of the present application is meant by pheniramine, pheniramine and its salts. In one embodiment, the salt is pheniramine maleate.

Chlorphenamine (or chlorpheniramine) (CAS 132-22-9) is an active ingredient used for its anticholinergic, sedative, antitussive, but especially antihistamine (it is a first-generation antihistamine with a sedative effect important). For example, it is often indicated to reduce symptoms associated with allergies such as hay fever or hives. The recommended daily dose (in adults) is about 24 mg.

In the context of the present application is meant by chlorphenamine (or chlorpheniramine) chlorphenamine and its salts. In one embodiment, the salt is chlorphenamine maleate.

[00030] Pseudoephedrine (CAS 90-82-4) is an active ingredient frequently used as a decongestant. It is used alone or in combination, particularly with an antihistamine and / or antipyretic (eg paracetamol, ibuprofen). The recommended daily dose (in adults) is about 120 to 240 mg.

In the context of the present application, pseudoephedrine is understood to mean pseudoephedrine and its salts. In one embodiment, the salt is selected from the group consisting of pseudoephedrine hydrochloride, pseudoephedrine sulfate, and mixtures thereof.

In the context of the present application, the active ingredients may have undergone a preparation or be mixed with excipients to facilitate their implementation, for example paracetamol coated with pregelatinized starch or mixed with copovidone.

Their crystalline forms may also have been selected for their ability to direct compression, for example the orthorhombic form of paracetamol.

In the context of the present application, the "active phase" is the portion of the powder mixture for preparing the tablet or tablet consisting of the active ingredients. For example, a mixture of powders for preparing the tablet or a 1600 mg tablet comprising 500 mg of paracetamol, 200 mg of vitamin C and 25 mg of pheniramine comprises 500 + 200 + 25 = 725 mg of active phase, and therefore 1600 - 725 = 875 mg of what is called in the context of the present application a "excipient phase". As illustrated above, the active phase represents about 45% of the total mass of the powder mixture to prepare the tablet or the total mass of the tablet.

As explained above, a particularly suitable dosage form is a dispersible tablet but many difficulties are to be solved to prepare such a tablet.

The first problem is the preparation of galenic forms, the active phase will represent a large part of the tablet, the latter resulting from the addition of the different active ingredients.

Other problems may also arise from significant differences in the mass contents of active ingredients that will have a negative influence on the necessary homogenous distribution of the active ingredients within the chosen dosage form.

Compatibility or stability problems may also arise and be exacerbated by the techniques used for the preparation of dosage forms comprising several active ingredients.

The European Pharmacopoeia imposes, in terms of disintegration, a strict specification and given this disintegration constraint, the excipients used must be sensitive to moisture.

This sensitivity to moisture will cause: - a difficulty in using processes such as so-called wet granulation; - Potential problems of stability of the final form that can not include a coating that would affect the speed of disintegration.

However, differences in levels of active principles and compatibility problems between the various active principles guide the skilled person to the use of granulation to obtain a uniform distribution of active ingredients, including those present in the art. lower quantities.

However, surprisingly, it has been demonstrated by the applicant that the use of wet granulation or dry granulation did not meet the stability criteria.

Indeed, the active ingredients in mixture revealed instability to heat and moisture. Active degradation products have been found in wet granulation tests because of the oxidation phenomena caused by the joint presence of water and heat.

Degradation products have also been demonstrated during dry granulation tests because of the heat input of this technique to the powder, and then during the formation of granules.

In contrast despite the mixing and homogenization phases, surprisingly no significant presence of degradation products was detected during the implementation of the direct compression technique of a mixture of powders.

Even more surprisingly only the preparation of a powder for direct compression has made it possible to obtain a tablet that makes it possible to satisfy at the same time the criteria of stability and of homogeneity of the distributions of the active ingredients in the final tablet corresponding to the requirements of the European Pharmacopoeia (Ph. Eur.), and the dispersibility criterion according to the requirements of the Ph. Eur.

This ability to manufacture a direct compression powder whose active phase comprises at least two active ingredients has been applied to the manufacture of a powder whose active phase comprises a third active ingredient. More particularly, it has been applied to powders for direct compression whose ratios of the contents of active principles in mass of the total mass of said tablet are greater than 10.

More particularly, it has been applied to powders for direct compression whose ratios of the contents of active ingredients in mass of the total mass of said tablet are greater than 20.

The invention relates to a mixture of powders for direct compression, characterized in that it comprises: an active phase representing at least 30% by weight of the total mass of the powder mixture comprising at least, in combination with paracetamol and vitamin C, and at least one disintegrator.

The invention also relates to a dispersible tablet obtained by direct compression, characterized in that it comprises the mixture of powders according to the invention.

The invention also relates to a dispersible tablet obtained by direct compression of a mixture of powders according to the invention.

In one embodiment, the active phase represents at least 40% by weight of the total mass of the mixture of powders for direct compression or the total mass of the tablet obtained by direct compression.

In one embodiment, the active phase represents at least 45% by weight of the total mass of the mixture of powders for direct compression or the total mass of the tablet obtained by direct compression.

In one embodiment, the ratios of the mass contents of active ingredients within the active phase are greater than 10.

In one embodiment, the ratios of the mass contents of active ingredients within the active phase are greater than 20.

In one embodiment, said at least one disintegrant is selected from the group consisting of crospovidone, croscarmellose, sodium starch glycolate, and mixtures thereof.

In one embodiment, said at least one disintegrant further comprises povidone.

In one embodiment, said at least one disintegrant is crospovidone.

In one embodiment, said at least one disintegrant is a mixture of crospovidone and povidone.

In one embodiment, a tablet whose total mass is about 1600 mg comprises between 150 and 250 mg of disintegrant.

In one embodiment, a tablet whose total mass is about 1600 mg comprises 216 mg of disintegrant.

In one embodiment, a tablet whose total mass is about 800 mg comprises between 75 and 125 mg of disintegrant.

In one embodiment, a tablet whose total mass is about 1600 mg comprises 108 mg of disintegrant.

In one embodiment, the mass percentage of disintegrant is between 9 and 16% by weight of the total mass of the mixture of powders for direct compression or the total mass of the tablet obtained by direct compression.

In one embodiment, the mixture of powders for direct compression or the dispersible tablet obtained by direct compression according to the invention is characterized in that it further comprises a diluent.

In one embodiment, said diluent is selected from the group consisting of microcrystalline cellulose, mannitol, and their mixture.

In one embodiment, said diluent is microcrystalline cellulose.

In one embodiment, a tablet whose total mass is about 1600 mg comprises between 200 and 750 mg of diluent.

In one embodiment, a tablet whose total mass is about 800 mg comprises between 100 and 375 mg of diluent.

In one embodiment, the mass percentage of diluent is between 12 and 47% by weight of the total mass of said tablet.

In one embodiment, a tablet whose total mass is about 1600 mg comprises between 200 and 1200 mg of paracetamol and between 50 and 500 mg of vitamin C.

In one embodiment, a tablet whose total mass is about 1600 mg comprises between 200 and 750 mg of paracetamol and between 50 and 300 mg of vitamin C.

In one embodiment, a tablet having a total mass of about 1600 mg comprises about 280 mg of paracetamol and about 100 mg of vitamin C.

In one embodiment, a tablet having a total mass of about 1600 mg comprises about 500 mg of paracetamol and about 200 mg of vitamin C.

In one embodiment, a tablet whose total mass is about 800 mg comprises between 100 and 600 mg of paracetamol and between 25 and 250 mg of vitamin C.

In one embodiment, a tablet whose total mass is about 1600 mg comprises between 100 and 375 mg of paracetamol and between 25 and 150 mg of vitamin C.

In one embodiment, a tablet whose total mass is about 800 mg comprises about 250 mg of paracetamol and about 100 mg of vitamin C.

In one embodiment, the mixture of powders for direct compression or the dispersible tablet obtained by direct compression according to the invention is characterized in that the mass percentage of paracetamol is between 12.5 and 75% by weight of the total mass of the mixture of powders for direct compression or the total mass of the tablet obtained by direct compression and the mass percentage of vitamin C is between 3.1 and 31.2% by weight of the total mass of the powder mixture for direct compression or the total mass of the tablet obtained by direct compression.

In one embodiment, the mass percentage of paracetamol is between 12.5 and 46.9% by weight of the total mass of the mixture of powders for direct compression or the total mass of the tablet obtained by direct compression, and the mass percentage of vitamin C is between 3.1 and 18.7%, by mass of the total mass of the mixture of powders for direct compression or the total mass of the tablet obtained by direct compression.

In one embodiment, the mass percentage of paracetamol is about 31% by weight of the total mass of the mixture of powders for direct compression or the total mass of the tablet obtained by direct compression, and the mass percentage of Vitamin C is about 6% by weight of the total mass of the direct compression powder mixture or the total mass of the direct compression tablet.

In one embodiment, vitamin C is a microcrystalline vitamin C.

The invention also relates to a mixture of powders for direct compression, characterized in that it comprises in its active phase in addition at least one third active ingredient selected from the group consisting of pheniramine, chlorphénamine, pseudoephedrine and their associations.

In this embodiment, the invention also relates to a dispersible tablet obtained by direct compression, characterized in that it comprises the mixture of powders further comprising at least one third active ingredient selected from the group consisting of pheniramine , chlorphenamine, pseudoephedrine and their combinations.

In one embodiment, the weight percentage of the third active ingredient is between 0.1 and 5% by weight of the total mass of the mixture of powders for direct compression or the total mass of the tablet obtained by direct compression.

In one embodiment, the third active ingredient is pheniramine.

In one embodiment, the weight percentage of pheniramine is between 0.3 and 3% by weight of the total mass of the mixture of powders for direct compression or the total mass of the tablet obtained by direct compression.

In one embodiment, the mass percentage of pheniramine is about 1.6% by weight of the total mass of the mixture of powders for direct compression or the total mass of the tablet obtained by direct compression.

In one embodiment, a tablet whose total mass is about 1600 mg comprises between 5 and 50 mg of pheniramine.

In one embodiment, a tablet whose total mass is about 1600 mg comprises about 25 mg of pheniramine.

In one embodiment, a tablet whose total mass is about 800 mg comprises between 2.5 and 25 mg of pheniramine.

In one embodiment, a tablet whose total mass is about 800 mg comprises about 10 mg of pheniramine.

In one embodiment, a tablet whose total mass is about 1600 mg comprises between 5 and 50 mg of pheniramine.

In one embodiment, a tablet whose total mass is about 1600 mg comprises about 25 mg of pheniramine.

In one embodiment, a tablet whose total mass is about 800 mg comprises between 2.5 and 25 mg of pheniramine.

In one embodiment, a tablet whose total mass is about 800 mg comprises about 10 mg of pheniramine.

In one embodiment, said pheniramine is in the form of pheniramine maleate.

In one embodiment, the third active ingredient is chlorphenamine.

In one embodiment, the mass percentage of chlorphenamine is between 0.1 and 0.5% by weight of the total mass of the mixture of powders for direct compression or the total mass of the tablet obtained by direct compression.

In one embodiment, the mass percentage of chlorphenamine is about 0.25% by weight of the total mass of the mixture of powders for direct compression or the total mass of the tablet obtained by direct compression.

In one embodiment, the mass percentage of pseudoephedrine is between 1 and 5% by weight of the total mass of the mixture of powders for direct compression or the total mass of the tablet obtained by direct compression.

In one embodiment, the mass percentage of pseudoephedrine is about 3.75% by weight of the total mass of the mixture of powders for direct compression or the total mass of the tablet obtained by direct compression.

The invention also relates to a mixture of powders for direct compression or a dispersible tablet obtained by direct compression, characterized in that it further comprises at least one excipient chosen from flavoring agents, lubricants and sweetening agents. , flow agents, as well as dyes.

The invention also relates to a mixture of powders for direct compression or a dispersible tablet obtained by direct compression, characterized in that it comprises in its excipient phase in addition at least one flavoring agent.

In one embodiment, the flavoring agent is an unencapsulated flavor selected from the group consisting of Orange juice flavor 501202 TP0551, lemon aroma SBD213841, aroma lemon SD 290252, and mixtures thereof.

The invention also relates to a mixture of powders for direct compression or a dispersible tablet obtained by direct compression, characterized in that it comprises in its excipient phase furthermore at least one lubricant.

In one embodiment, said lubricant is selected from the group consisting of sodium stearyl fumarate, magnesium stearate, talc, polyethylene glycol, glycerol behenate, and mixtures thereof.

[000107] In one embodiment, said lubricant is sodium stearyl fumarate.

The invention also relates to a mixture of powders for direct compression or a dispersible tablet obtained by direct compression, characterized in that it comprises in its excipient phase furthermore at least one sweetening agent.

In one embodiment, said sweetening agent is selected from the group consisting of sucralose, sucrose, aspartame and mixtures thereof.

[000110] The invention also relates to a mixture of powders for direct compression or a dispersible tablet obtained by direct compression, characterized in that it comprises in its excipient phase furthermore at least one flow agent.

[000111] In one embodiment, said flow agent is selected from the group consisting of colloidal silica anyhdre cellulose powder, magnesium oxide, magnesium silicate, talc, and mixtures thereof.

In one embodiment, said flow agent is colloidal silica anyhdre.

The invention also relates to a mixture of powders for direct compression or a dispersible tablet obtained by direct compression, characterized in that it comprises in its excipient phase in addition at least one coloring agent.

In one embodiment, said coloring agent is selected from the group consisting of FD & C yellow dye, riboflavin (E101), Sunset Yellow PCF (E110), and mixtures thereof.

The invention also relates to a mixture of powders for direct compression or a dispersible tablet obtained by direct compression, characterized in that it comprises at least one mixture of riboflavin (E101) and Sunset Yellow PCF staining agents (E110 ).

The invention also relates to a dispersible tablet according to the invention, intended to be used in case of pain and / or fever such as headaches, and / or flu, and / or dental pain, and / or body aches and / or painful rules.

The invention also relates to a dispersible tablet according to the invention, intended to be used at a frequency of more than 4 hours between taps.

[000118] The invention also relates to a dispersible tablet according to the invention, characterized in that said tablet is hydro-dispersible.

[000119] The invention also relates to a dispersible tablet according to the invention, characterized in that said tablet is orodispersible.

The invention also relates to a method of manufacturing a dispersible tablet according to the invention, by direct compression, characterized in that it comprises the following steps: 1) preparation of a mixture A comprising at least said vitamin C and said disintegrant; 2) mixing mixture A with paracetamol to obtain a mixture of powders according to the invention; 3) compression of the mixture of powders obtained.

In one embodiment, the method is characterized in that it further comprises a lubricating step between steps 2 and 3, said step consisting in the addition of a lubricant, said lubricant being chosen from the group consisting of sodium stearyl fumeate, magnesium stearate, talc, polyethylene glycol, glycerol behenate, and mixtures thereof.

[000122] In one embodiment, said lubricant is sodium stearyl fuma spleen.

[000123] In one embodiment, said lubricant is glycerol behenate.

In one embodiment, said mixture A further comprises at least pheniramine.

EXAMPLES

Example 1 Composition of a Disoergetable Tablet According to the Invention

TABLE 1 [000125] The composition shown in Table 1 is a composition intended primarily for use in adults.

The composition shown in Table 1 comprises 725 mg of active phase and 875 mg of excipient phase, ie about 45% of active phase and about 55% of excipient phase.

The composition shown in Table 1 can be adapted for use in children, including, for example, the following doses of active ingredients: paracetamol 280 mg, vitamin C 100 mg, pheniramine 10 mg.

Example 2 Composition of a Disoergetable Tablet According to the Invention

TABLE 2 [000128] The composition shown in Table 2 is a composition intended primarily for use in children.

[000129] The composition shown in Table 2 comprises 380 mg of active phase and 420 mg of excipient phase, ie about 47% of active phase and about 53% of excipient phase.

ExemaLe3_jj: mmQsjtjOT ^ dispersible according to the invention

TABLE 3 [000130] The composition shown in Table 3 is a composition intended mainly for use in adults.

The composition shown in Table 3 comprises 704 mg of active phase and 896 mg of excipient phase, ie about 44% of active phase and about 56% of excipient phase.

Example 4: Evaluation of the uniformity of the contents of active principles.

These tests were performed on the mixture of powders and the tablets obtained by direct compression.

Tests on the mixture of powders: [000133] 10 samples were taken on 3 batches of final mixture of powders immediately before the implementation of the compression step.

The active ingredients were determined according to the methods described in the European Pharmacopoeia and the results obtained are collated in the following Table 4.

* RSD: Standard deviation TABLE 4 [000134] The homogeneity of the content of the different active ingredients is clearly obtained after mixing.

Tests on dispersible tablets: [000135] The method described in the European Pharmacopoeia part 2.9.40 "Uniformity of single-dose preparations" was applied to three series of sampling in 3 batches of dispersible tablets of different manufactures.

The active ingredients in the dispersible tablets were determined according to the methods described in the European Pharmacopoeia and the results obtained are collated in the following Table 5.

"VA" represents the acceptance value as defined European Pharmacopoeia part 2.9.40 "Uniformity of single-dose preparations".

* RSD: Standard deviation TABLE 5 [000138] The homogeneity of content of the different active ingredients in each batch of dispersible tablets is clearly obtained after compression.

EXAMPLE 5 Disintegration Test of a Dispersible Tablet According to the Invention A tablet disintegration test obtained according to Example 1 was carried out according to the monograph of Ph. Eur., Version 8.0.

Each collected tablet is immersed in water at room temperature (about 20 ° C).

After three minutes, it is found that the tablet is completely dispersed in water.

[000142] A tablet disintegration test obtained according to Example 2 was carried out according to the monograph of the Ph. Eur., Version 8.0.

Each tablet is immersed in water at room temperature (about 20 ° C).

After three minutes, it is found that the tablet is completely dispersed in water.

[000145] A tablet disintegration test obtained according to Example 3 was carried out according to the monograph of the Ph. Eur., Version 8.0.

Each collected tablet is immersed in water at room temperature (about 20 ° C).

After three minutes, it is found that the tablet is completely dispersed in water.

In conclusion, the tablets of Examples 1 to 3 correspond to the specifications, in particular with regard to disintegration, of the Ph. Eur monograph. They correspond both to the specifications of the dispersible tablet (called in the context of present "hydro-dispersible" tablet application) and orodispersible tablet.

Claims (12)

1. Mixture of powders for direct compression, characterized in that it comprises: an active phase representing at least 30% by weight of the total mass of the mixture of powders comprising at least, in combination with paracetamol and vitamin C, and - at least one disintegrator. Disperseible tablet obtained by direct compression, characterized in that it comprises the mixture of powders according to claim 1. 3. Mixture of powders for direct compression according to claim 1 or dispersible tablet according to claim 2, characterized in that the mass percentage of disintegrant is between 9 and 16% by weight of the total mass of said mixture of powders or said tablet. 4. Mixture of powders for direct compression according to claim 1 or 3, or dispersible tablet according to claim 2 or 3, characterized in that it further comprises a diluent. 5. A mixture of powders for direct compression or dispersible tablet according to the preceding claim, characterized in that said diluent is selected from the group consisting of microcrystalline cellulose, mannitol, and their mixture. 6. Mixture of powders for direct compression or dispersible tablet according to any one of claims 4 to 5, characterized in that the mass percentage of diluent is between 12 and 47% by weight of the total mass of said mixture of powders or said compressed. 7. Mixture of powders for direct compression or dispersible tablet according to any one of the preceding claims, characterized in that the mass percentage of paracetamol is between 12.5 and 75% by weight of the total mass of said mixture of powders or said tablet, and the mass percentage of vitamin C is between 3.1 and 31.2%, by mass of the total mass of said mixture of powders or said tablet. 8. Mixture of powders for direct compression or dispersible tablet according to any one of the preceding claims, characterized in that vitamin C is a microcrystalline vitamin C. 9. Mixture of powders for direct compression or dispersible tablet according to any one of the preceding claims, characterized in that it comprises in its active phase in addition at least one third active ingredient selected from the group consisting of pheniramine, chlorphenamine, pseudoephedrine and their combinations. 10. Mixture of powders for direct compression or dispersible tablet according to claim 9, characterized in that the third active ingredient is pheniramine. 11. Mixture of powders for direct compression or dispersible tablet according to claim 10, characterized in that the weight percentage of pheniramine is between 0.3 and 3% by weight of the total mass of said powder mixture or said tablet. 12. A method of manufacturing a dispersible tablet according to any one of claims 2 to 11, characterized in that it comprises the following steps: 1) preparation of a mixture A comprising at least said vitamin C and said disintegrant; 2) mixing the mixture A with paracetamol to obtain a mixture of powders according to any one of claims 1 or 3 to 11; 3) compression of the powder mixture obtained in 2) to obtain a dispersible tablet.