WO2024144678A1

WO2024144678A1 - Orally disintegrating tablets (odt) formulations for the treatment of flu, common cold and allergic symptoms

Info

Publication number: WO2024144678A1
Application number: PCT/TR2023/051691
Authority: WO
Inventors: Emrah ÖZAKAR; Rukiye Sevinç ÖZAKAR; Saim Enes ÖZDEM
Original assignee: Atatürk Üni̇versi̇tesi̇ Fi̇kri̇ Mülki̇yet Haklari Koordi̇natörlüğü Döner Sermaye İşletmesi̇
Priority date: 2022-12-27
Filing date: 2023-12-25
Publication date: 2024-07-04

Abstract

The invention relates to formulations combining the active ingredients dexketoprofen trometamol, which is one of the non-steroidal anti-inflammatory drugs (NSAIDs) used in the treatment of anti-inflammatory diseases, with a strong analgesic and anti-inflammatory effect; Pseudoephedrine HCl, which is frequently used as a decongestant in the symptomatic treatment of influenza and common cold; Desloratadine, an antihistamine frequently used in the relief of allergic rhinitis and symptoms; and vitamin C (Ascorbic acid), which are also used as a vitamin supplement in the treatment of common cold and flu, in an orodispersible tablet (orodispersible tablet, oral disintegrating tablet, ODT) prepared by direct compression method and provides solutions to many problems at the same time.

Description

ORALLY DISINTEGRATING TABLETS (ODT) FORMULATIONS FOR THE TREATMENT OF FLU, COMMON COLD AND ALLERGIC SYMPTOMS

Field of the Invention

The invention relates to formulations developed for oral use in fast disintegrating tablet form (orodispersible tablets, oral disintegrating tablets, ODT) which are one of the new generation tablet forms, combining the dexketoprofen trometamol which is a potent non-steroidal antiinflammatory drug (NSAID) used in the treatment of anti-inflammatory diseases, pseudoephedrine HCI, which is frequently used as a decongestant in the symptomatic treatment of influenza and common cold, desloratadine which is an antihistamine frequently used in the treatment of allergic rhinitis and symptoms, vitamin C (ascorbic acid) as a vitamin supplement frequently used in the treatment of common cold and flu, and aims to solve multiple problems at the same time and makes it an advantageous product in terms of both economic and patient compliance

State of the Art

Upper respiratory tract infections are infections that occur in the nose, pharynx, larynx and sinuses caused by bacteria and viruses. These infections cause diseases such as acute bronchitis, flu, common cold and respiratory distress syndromes. In these diseases, symptoms such as runny nose, itching in the nose and eyes, nasal congestion, sinus pain, fever, weakness, cough, shortness of breath, muscle pains, sore throat and difficulty swallowing may occur.

NSAIDs essentially block the enzyme cyclooxygenase-2 (COX-2), reducing inflammation, pain, and fever. Due to this effect, non-steroidal anti-inflammatory agents are widely used in the treatment of muscle pain, weakness and headache in many upper respiratory tract diseases. Dexketoprofen is the enantiomer of ketoprofen. It has analgesic and antiinflammatory effects by inhibiting COX enzymes. Dexketoprofen trometamol, which is the trometamine salt of dexketoprofen, is absorbed in a short time and provides rapid emergence of analgesic and anti-inflammatory effect.

Hi histamine receptor antagonists, called classic antihistamines, are used in local anaphylaxis-induced urticaria and angioedema, seasonal allergic rhinitis, nasal discharge, sneezing, itching sensation in the nose and throat, reducing nasal discharge in common cold, travel-sickness, and to create premedication and sedation. Classic antihistamines are classified as first-generation antihistamines that easily cross the blood-brain barrier which produce sedation, and second-generation antihistamines that cross the blood-brain barrier relatively rarely which do not produce sedation.

Antihistamines and decongestants are used in the treatment of nasal discharge and nasal congestion symptoms in influenza and upper respiratory tract infections. While antihistamines eliminate edema caused by increased vascular permeability; they reduce nasal discharge, sneezing, watering and itching in the eyes. The use of the second- generation Hi receptor antagonist, desloratadine, reduces symptoms such as sneezing, nasal discharge and itching caused by histamine H1 receptor stimulation.

Decongestants, relieve nasal obstruction by vasoconstriction of the vessels in the upper respiratory tract. Pseudoephedrine hydrochloride is an alpha-adrenergic agonist used as a decongestant in respiratory tract diseases. With the use of decongestant drugs, the airway is opened and the sinuses are allowed to breathe by the stuffiness of the nose being removed. Decongestants, which are used as a single drug in serous otitis media, are used in addition to antibacterial treatment to open the eustachian tube. While oral decongestants show their decongestion effects in the nasal throat mucosa for a longer time and in a wider area, swelling and edema due to irritation caused by long-term use of nasal decongestants are less common.

Vitamin C plays a role in reducing oxidative stress, supporting immunity and enzyme activation. There is also evidence that vitamin C prevents respiratory tract diseases. Vitamin C is thought to reduce the duration and severity of common cold and allergy symptoms caused by histamine by providing the breakdown of the imidazole ring in the structure of the histamine molecule. As a matter of fact, after 2 weeks of vitamin C supplementation, 2 g per day, plasma histamine levels of healthy individuals have decreased by 40%. In addition, vitamin C's increase in chemoxia is also effective in reducing the severity of common cold symptoms.

Oral drug administration is the most preferred drug administration method since it is simple, painless, inexpensive and has high patient compliance. The main formulations used for oral drug administration are solid dosage forms (such as tablets and capsules) and liquid dosage forms (such as solutions and suspensions). Liquid dosage form factors such as the inability to control the release properties, stability problems, and high storage-transport fees from production to the service of patients have increased the number of studies on the production of solid dosage forms instead of liquid dosage forms. Tablets are a chemical mechanically and microbiologically stable dosage form with high dose homogeneity. At the same time, Tablets are the lightest, cheapest to transport and easiest to package oral dosage form among other dosage forms. Pediatric, geriatric and bedridden patients, psychiatric patients who refuse to swallow, and patients who cannot easily access water during travel who are forced to use solid dosage forms such as traditional tablets and capsules have difficulty using their medications. In addition, the irritant nature of some drugs, their disintegration in the gastrointestinal system, their bad taste and the change in their absorption with food limits the use of drugs orally. In recent years, oral disintegrating tablets, which dissolve or disperse rapidly in the mouth within seconds that do not require the use of water for easy swallowing of drugs have been frequently used by the pharmaceutical industry.

In the European Pharmacopoeia, oral disintegrating tablets (orodispersible tablets) are defined as "uncoated tablets that are placed in the mouth and rapidly disintegrate in the mouth before swallowing." In the disintegration test, the expression "orodispersible tablets (ODT) disintegrate within 3 minutes when water is used as liquid medium." is used. With ODT, which offers many advantages, the patient compliance is improved and an economic advantage is provided compared to other solid dosage forms.

The invention includes orally rapidly disintegrating tablet (ODT) formulations comprising a combination of 4 active substances that can be used to treat allergic symptoms, nasal and throat congestion, and body pain and malaise, which are especially common in winter with influenza and upper respiratory tract infections.

The old technique/method has the following disadvantages: i. There is no drug form comprising Dexketoprofen trometamol; Pseudoephedrine HCI; Desloratadine and Vitamin C (Ascorbic acid) together. ii. Considering the common benefits of these 4 active substances in the acute and chronic treatment of diseases in influenza and upper respiratory tract infections accompanied by nasal congestion and allergic symptoms, the purchase and use of separate conventional tablets or capsules continue. iii. Being economically disadvantageous as a result of using these 4 drug substances separately, which we have combined in a single tablet with the ODTs we have prepared, iv. When these 4 active substances with their anti-inflammatory, analgesic, antihistaminic, decongestant activities are taken together with vitamin C, they have a synergistic effect. However, today, all of them are offered individually or in binary combinations, v. Considering the current forms of these three substances, the inability to produce a rapid pharmacological effect, vi. Some patient groups, especially pediatric and geriatric patients, have difficulty swallowing or chewing solid dosage forms. Many pediatric and geriatric patients cannot use solid dosage forms (tablets, capsules) due to fear of suffocation (dysphagia), vii. Inability to use without water, viii. Inadequacy of conventional tablets and capsules in cases where the pharmacological effect is desired to be started as soon as possible,

Oral drug administration is the most preferred drug administration route as it provides simple, non-interventional, painless, cost-effective and high patient compliance. Tablets are the oral dosage form can provide high-dose homogeneity and has the best content uniformity among all oral dosage forms. In addition, the dosage form with the most appropriate production cost among all oral dosage forms is tablets. However, this method, which is difficult to apply for the child and elderly population, is also troublesome for all patient groups experiencing swallowing problems.

It is also important to eliminate the psychological factors brought by tablet/capsule swallowing for patients of all age groups who have difficulty swallowing, which we call "Dysphagia". Apart from this, it is not possible to use conventional solid dosage forms (tablets, capsules) without requiring water. They cannot be used during the travel or in cases where water cannot be reached. In addition, the major disadvantage of this dosage form is that the pharmacological effects of the drug cannot be observed immediately. The time it takes for them to reach the stomach and disintegrate/dissolve and the pharmacological effect to emerge takes 30 to 60 minutes on average.

When the studies in the current technique are examined, it is seen that there is a need for formulations developed for oral use, which aim to solve more than one problem at the same time and make it an advantageous product in terms of both economic and patient compliance.

Detailed Description of the Invention

In this description, the development of sublingual tablet formulations containing a corticosteroid in combination with an antihistamine used in the treatment of allergic diseases is described for a better understanding of the subject and in a manner that does not have any limiting effect.

The invention is ODT formulations prepared using direct compression technique, which comprises dexketoprofen trometamol, which has a strong analgesic and anti-inflammatory activity; pseudoephedrine HCI, which is frequently used as a decongestant in the symptomatic treatment of influenza and common cold; desloratadine, an antihistamine frequently used in the relief of allergic rhinitis and its symptoms; and vitamin C (ascorbic acid), which is used as a vitamin supplement in the treatment of common cold and flu.

The invention is preferably orally disintegrating tablet (ODT) formulations comprising a combination of 4 active substances that can be used in the treatment of allergic symptoms, nasal and throat congestion, and pain and malaise occurring in the body, especially in conjunction with influenza and upper respiratory tract infections, which are common in winter.

The invention is preferably orally disintegrating tablet (ODT) formulations that can be used in the treatment of flu, common cold and allergic symptoms.

The primary purpose of the invention is to comprise 4 active substances together for the first time and to respond to many disease symptoms with a single tablet. In addition, it provides ease of use for patients and increases the quality of life of patients.

Another purpose of the invention is to correct all disease-causing factors in influenza and upper respiratory tract infections accompanied by nasal congestion and allergic symptoms in today's fast living conditions as soon as possible.

Another object of the invention is to provide alternative and ease of use in patients with dysphagia (geriatric, pediatric, bedridden and mentally disabled).

Another object of the invention is to use it easily without the need for water. Another object of the invention is that it can be used at any time and in any environment, especially while traveling by vehicle, since water is not needed.

Another object of the invention is to accelerate the onset of the pharmacological effect.

Another object of the invention is to be superior to the old dosage forms in terms of reducing the expenditure paid for 4 different drugs economically.

Another object of the invention is that there is no risk of choking.

Another object of the invention is to exhibit improved stability.

Another object of the invention is to leave little or no residue in the mouth after the application.

Another object of the invention is to comprise a low dose and a low possibility of side effects.

Another object of the invention is to provide a more accurate dose when compared to liquid dosage forms.

Another object of the invention is to offer improved bioavailability for less water-soluble drugs by offering a large surface area while dissolving rapidly.

Another object of the invention is that it does not prevent normal functions such as speaking and drinking.

The formulation as oral rapidly disintegrating tablet dosage in its simplest form, basically comprises the combination of dexketoprofen trometamol; pseudoephedrine HCI; desloratadine and vitamin C (ascorbic acid). In the invention, the preferable dexketoprofen trometamol; pseudoephedrine HCI; desloratadine and vitamin C ratio is preferably 5:6:1 :5. All developed formulations comprise the same amount of dexketoprofen trometamol; pseudoephedrine HCI; desloratadine and vitamin C.

The invention, which is in the form of a tablet that disintegrates rapidly in the mouth, is placed on the tip or base of the tongue and wetted with saliva within 30 to 60 seconds. In this way, the drug substances contained in the tablet are released and dispersed and/or dissolved for local and/or systemic absorption. The developed invention is in the form of drug dosage forms that contain both active substances at the same time and offer a rapid onset of action.

All active substances and excipients used in the developed formulation are water-soluble or dispersible. In other words, these prepared ODTs can dissolve/disperse very quickly with saliva when placed on the base or tip of the tongue. Therefore, it can be used without the need for water and without difficulty in swallowing. In this way, both a rapid onset of action occurs and the patient's complaints are responded to in a short time. Because its permeability is high due to the thin membrane structure of the sublingual and buccal mucosa as well as the fact that it has a lot of blood vessels. Due to this rapid blood flow, there is also a very rapid bioavailability. This rapid bioavailability is due to skipping the first-pass effect and better permeability. In addition, the large surface area and ease of application for absorption make the oral mucosa a very effective and selective way of systemic drug transport. The formulations developed preferably comprises 25 mg of Dexketoprofen trometamol, 30 mg of Pseudoephedrine HCI, 5 mg of Desloratadine and 25 mg of vitamin C. In this way, it is ensured that individuals of all age groups can easily take these drugs without taking tablets or capsules, by placing them on the tip or base of the tongue in a combined form without requiring water.

In the formulations, only dexketoprofen trometamol, pseudoephedrine HCI, desloratadine and vitamin C cannot be replaced by another chemical drug.

The formulation developed in a preferred embodiment of the invention preferably comprises at least one excipient specified below in accordance with the amounts given in Tables 1 -7 for tablets prepared by the "direct compression technique": i. Sucralose, sodium saccharin, aspartame, stevia, glucose, maltose, dextrose, mannitol, sorbitol (70%) or acesulfame may be used (more preferably sodium saccharin), ii. Sucralose, sodium saccharin, aspartame, stevia, glucose, maltose, dextrose, mannitol, sorbitol (70%) or acesulfame may be used (more preferably sucralose), iii. Xanthan gum, sodium starch glycolate, kollidon cl, crospovidone, croscarmellose sodium, hydroxypropyl cellulose, Ac-Di-Sol®, solutab ®, nymce ZSX®, primellose®, vivasol®, polyplasdone®, explotab®, primojel®, satialgine®, sodium bicarbonate can be used (more preferably Kollidon CL), iv. Xanthan gum, sodium starch glycolate, kollidon CL, crospovidone, croscarmellose sodium, hydroxypropyl cellulose, Ac-Di-Sol®, solutab ®, nymce ZSX®, primellose®, vivasol®, polyplasdone®, explotab®, primojel®, satialgine®, sodium bicarbonate can be used (more preferably croscarmellose sodium) v. Pregelatinized starch, calcium phosphate, mannitol, sorbitol, calcium sulfate and corn starch, rice starch, microcrystallized cellulose, avicel PH 101 , avicel PH 102, avicel PH 103, avicel PH 107, avicel® CE 15, avicel LM200/MCC, pearlitol 200 SD, microcel, emcocel, sucrose, dextrose, pearlitol® can be used (more preferably Pearlitol 200 SD), vi. Pregelatinized starch, calcium phosphate, mannitol, sorbitol, calcium sulfate and corn starch, rice starch, microcrystallized cellulose, avicel DG, avicel PH 101 , avicel PH 102, avicel PH 103, avicel PH 107, avicel® CE 15, microcel, emcocel, sucrose, dextrose, pearlitol® can be used (more preferably Avicel® DG), vii. Avicel PH LM200/MCC, pregelatinized starch, calcium phosphate, mannitol, sorbitol, calcium sulfate and corn starch, rice starch, microcrystallized cellulose, avicel PH 101 , avicel PH 102, avicel PH 103, avicel PH 107, avicel® CE 15, microcel, emcocel, sucrose, dextrose, pearlitol® can be used (more preferably Avicel® PH 101 ), viii. Avicel PH LM200/MCC, pregelatinized starch, calcium phosphate, mannitol, sorbitol, calcium sulfate and corn starch, rice starch, microcrystallized cellulose, avicel PH 101 , avicel PH 102, avicel PH 103, avicel PH 107, avicel® CE 15, microcel, emcocel, sucrose, dextrose, pearlitol® can be used (more preferably Avicel® PH 102), ix. Magnesium stearate, sterotex, talc, stearic acid, PEG derivatives, surfactants, corn starch may be used (more preferably magnesium stearate), x. Magnesium stearate, sterotex, talc, stearic acid, PEG derivatives, surfactants, corn starch may be used (more preferably talc), xi. Magnesium stearate, sterotex, talc, stearic acid, PEG derivatives, surfactants, corn starch may be used (more preferably Sterotex). Table 1.

Table 2.

Table 3.

Table 4.

Table 5.

Table 6.

Table 7.

The formulation developed in a preferred embodiment of the invention comprises dexketoprofen trometamol, pseudoephedrine HCI, desloratadine, vitamin C, magnesium stearate, talc, croscarmellose sodium, kollidon CL, sodium saccharin, sucralose and avicel DG.

The formulation developed in a preferred embodiment of the invention comprises dexketoprofen trometamol, pseudoephedrine HCI, desloratadine, vitamin C, sterotex, croscarmellose sodium, kollidon CL, sodium saccharin, sucralose and pearlitol 200 SD.

The formulation developed in a preferred embodiment of the invention comprises dexketoprofen trometamol, pseudoephedrine HCI, desloratadine, vitamin C, magnesium stearate, talc, croscarmellose sodium, kollidon CL, sodium saccharin, sucralose and avicel PH 101.

The formulation developed in a preferred embodiment of the invention comprises dexketoprofen trometamol, pseudoephedrine HCI, desloratadine, vitamin C, magnesium stearate, talc, croscarmellose sodium, kollidon CL, sodium saccharin, sucralose and avicel PH 102.

The "direct compression technique” in an exemplary embodiment of the formulation is prepared following the following steps: Weighing all the components of the formulation in a beaker on a sensitive scale with a sensitivity of at least 1 mg; performing powder processing by mixing the weighed chemicals in a significant order (volumetric analysis, Hausner ratio determination, printability index determination, flow time determination); mixing the weighed components preferably for at least 10 minutes; pressing the mixture in each tablet by making the necessary hardness and weight adjustments to comprise 25 mg dexketoprofen trometamol, 30 mg pseudoephedrine HCI, 5 mg desloratadine and 25 mg vitamin C in the formulations; storing it at room temperature away from moisture and light until it is used.

The subject of the invention is to comprise dexketoprofen trometamol, which can be used in the treatment of allergic symptoms, nasal and throat congestion and pain and malaise in the body seen with the upper respiratory tract infections, pseudoephedrine HCL, desloratadine and vitamin C in combination as oral rapidly disintegrating tablet (orodispersible tablets, orally disintegrating tablets, ODT) which are one of the new generation tablet forms.

Claims

1. A formulation in the form of an orally disintegrating tablet (ODT) dosage form, characterized by comprising; a combination of dexketoprofen trometamol; pseudoephedrine HCI; desloratadine and vitamin C (Ascorbic acid).

2. The formulation according to claim 1 , characterized in that; the ratio of dexketoprofen trometamol; pseudoephedrine HCI; desloratadine and vitamin C is 5:6:1 :5.

3. Formulation according to claim 1 prepared by lyophilization technique, characterized in by comprising; the following: i. At least one sweetener selected from the group comprising sucralose, sodium saccharin, aspartame, stevia, glucose, maltose, dextrose, mannitol, sorbitol (70%), acesulfame or a combination thereof, ii. At least one superdisintegrant selected from the group comprising Kollidon CL, xanthan gum, sodium starch glycolate, crospovidone, croscarmellose sodium, hydroxypropyl cellulose, Ac-Di-Sol®, solutab®, nymce ZSX®, primellose®, vivasol ®, Avicel® PH LM200/MCC, polyplasdone®, explotab®, primojel®, satialgine ®, sodium bicarbonate or a combination thereof, iii. At least one binder/filler selected from the group comprising pregelatinized starch, calcium phosphate, mannitol, sorbitol, calcium sulfate and corn starch, rice starch, microcrystallized cellulose, avicel PH 101 , avicel PH 102, avicel PH 103, avicel PH 107, avicel® CE 15, avicel LM200/MCC, pearlitol 200 SD, microcel, emcocel, sucrose, dextrose, pearlitol® or a combination thereof, iv. At least one binder/filler selected from the group comprising mannitol, PVP K-30, PVP K-25, avicel PH LM200/MCC, lactose monohydrate, pregelatinized starch, calcium phosphate, mannitol, sorbitol, calcium sulfate and corn starch, rice starch, microcrystallized cellulose, avicel PH 101 , avicel PH 102, avicel PH 103, avicel PH 107, avicel® CE 15, microcel, emcocel, HPMC-E15, HPMC-E50, sucrose, dextrose, pearlitol® or a combination thereof, v. At least glidant/stabilisant selected from the group comprising Glyceryl behenate, aerosil 200, magnesium stearate, talc, sodium stearyl fumarate, poloxamer 188, sucrose stearate, PEGs, hydrogenated castor/vegetable oil, sodium lauryl sulfate, calcium/zinc stearate, stearic acid, sodium stearate, sterotex or a combination thereof,

4. The formulation according to claim 3, characterized by comprising; sucralose as binder/filler.

5. The formulation according to claim 3, characterized by comprising; Avicel DG as binder/filler.

6. The formulation according to claim 3, characterized by comprising; Pearlitol 200 SD as binder/filler.

7. The formulation according to claim 3, characterized by comprising; Avicel PH 101 as binder/filler.

8. The formulation according to claim 3, characterized by comprising; Avicel PH 102 as binder/filler.

9. The formulation according to claim 3, characterized by comprising; sodium saccharin as sweetener.

10. The formulation according to claim 3, characterized by comprising; magnesium stearate as glidant/lubricant.

11. The formulation according to claim 3, characterized by comprising; talc as glidant/lubricant.

12. The formulation according to claim 3, characterized by comprising; sterotex as glidant/lubricant.

13. The formulation according to claim 3, characterized by comprising; croscarmellose sodium as superdisintegrant.

14. The formulation according to claim 3, characterized by comprising; Kollidon CL as superdisintegrant.

15. The formulation according to claim 3, characterized by comprising; dexketoprofen trometamol, pseudoephedrine HCI, desloratadine, vitamin C, magnesium stearate, talc, croscarmellose sodium, kollidon CL, sodium saccharin, sucralose and avicel DG.

16. The formulation according to claim 3, characterized by comprising; dexketoprofen trometamol, pseudoephedrine HCI, desloratadine, vitamin C, sterotex, croscarmellose sodium, kollidon CL, sodium saccharin, sucralose and pearlitol 200 SD.

17. The formulation according to claim 3, characterized by comprising; dexketoprofen trometamol, pseudoephedrine HCI, desloratadine, vitamin C, magnesium stearate, talc, croscarmellose sodium, kollidon CL, sodium saccharin, sucralose and avicel PH 101.

18. The formulation according to claim 3, characterized by comprising; dexketoprofen trometamol, pseudoephedrine HCI, desloratadine, vitamin C, magnesium stearate, talc, croscarmellose sodium, kollidon CL, sodium saccharin, sucralose and avicel PH 102.

19. The formulation according to claim 15, characterized by comprising; an amount of dexketoprofen trometamol between 5-20%, an amount of desloratadine between 0.5-5%, an amount of pseudoephedrine HCI between 5-20%, an amount of vitamin C between 5- 20%, an amount of magnesium stearate between 0.5-5%, an amount of talc between 0.5- 5%, an amount of croscarmellose sodium between 2.5-20%, an amount of kollidon CL between 5-20%, an amount of sodium saccharin between 0.5-5%, an amount of sucralose between 12.5-27.5% and an amount of avicel DG between 12.5-27.5% by total weight.

20. The formulation according to claim 19, characterized by comprising; 10% dexketoprofen trometamol, 2% desloratadine, 12% pseudoephedrine HCI, 10% vitamin C, 2% magnesium stearate, 2% talc, 8% croscarmellose sodium, 12% kollidon CL, 2% sodium saccharin, 20% sucralose and 20% avicel DG by total weight.

21. The formulation according to claim 15, characterized by comprising; an amount of dexketoprofen trometamol between 5-20%, an amount of desloratadine between 0.5-5%, an amount of pseudoephedrine HCI between 5-20%, an amount of vitamin C between 5- 20%, an amount of magnesium stearate between 0.5-5%, an amount of talc between 0.5- 5%, an amount of croscarmellose sodium between 5-20%, an amount of kollidon CL between 2.5-20%, an amount of sodium saccharin between 0.5-5%, an amount of sucralose between 12.5-27.5% and an amount of avicel DG between 12.5-27.5% by total weight.

22. The formulation according to claim 21 , characterized by comprising; 10% dexketoprofen trometamol, 2% desloratadine, 12% pseudoephedrine HCI, 10% vitamin C, 2% magnesium stearate, 2% talc, 12% croscarmellose sodium, 8% kollidon CL, 2% sodium saccharin, 20% sucralose and 20% avicel DG by total weight.

23. The formulation according to claim 16, characterized by comprising; an amount of dexketoprofen trometamol between 5-20%, an amount of desloratadine between 0.5-5%, an amount of pseudoephedrine HCI between 5-20%, an amount of vitamin C between 5- 20%, an amount of sterotex between 2-10%, an amount of croscarmellose sodium between 5-20%, an amount of kollidon CL between 5-20%, an amount of sodium saccharin between 0.5-5%, an amount of sucralose between 12.5-27.5% and an amount of pearlitol 200 SD between 12.5-27.5% by total weight.

24. The formulation according to claim 23, characterized by comprising; 10% dexketoprofen trometamol, 2% desloratadine, 12% pseudoephedrine HCI, 10% vitamin C, 4% sterotex, 10% croscarmellose sodium, 10% kollidon CL, 2% sodium saccharin, 20% sucralose and 20% avicel DG by total weight.

25. The formulation according to claim 17, characterized by comprising; an amount of dexketoprofen trometamol between 5-20%, an amount of desloratadine between 0.5-5%, an amount of pseudoephedrine HCI between 5-20%, an amount of vitamin C between 5- 20%, an amount of magnesium stearate between 0.5-5%, an amount of talc between 0.5- 5%, an amount of croscarmellose sodium between 2.5-20%, an amount of kollidon CL between 5-20%, an amount of sodium saccharin between 0.5-5%, an amount of sucralose between 12.5-27.5% and an amount of avicel PH 101 between 12.5-27.5% by total weight.

26. The formulation according to claim 25, characterized by comprising; 10% dexketoprofen trometamol, 2% desloratadine, 12% pseudoephedrine HCI, 10% vitamin C, 2% magnesium stearate, 2% talc, 8% croscarmellose sodium, 12% kollidon CL, 2% sodium saccharin, 20% sucralose and 20% avicel PH 101 by total weight.

27. The formulation according to claim 17, characterized by comprising; an amount of dexketoprofen trometamol between 5-20%, an amount of desloratadine between 0.5-5%, an amount of pseudoephedrine HCI between 5-20%, an amount of vitamin C between 5- 20%, an amount of magnesium stearate between 0.5-5%, an amount of talc between 0.5- 5%, an amount of croscarmellose sodium between 2.5-20%, an amount of kollidon CL between 2.5-20%, an amount of sodium saccharin between 0.5-5%, an amount of sucralose between 12.5-27.5% and an amount of avicel PH 101 between 12.5-27.5% by total weight.

28. The formulation according to claim 27, characterized by comprising; 10% dexketoprofen trometamol, 2% desloratadine, 12% pseudoephedrine HCI, 10% vitamin C, 2% magnesium stearate, 2% talc, 12% croscarmellose sodium, 8% kollidon CL, 2% sodium saccharin, 20% sucralose and 20% avicel PH 101 by total weight.

29. The formulation according to claim 18, characterized by comprising; an amount of dexketoprofen trometamol between 5-20%, an amount of desloratadine between 0.5-5%, an amount of pseudoephedrine HCI between 5-20%, an amount of vitamin C between 5- 20%, an amount of magnesium stearate between 0.5-5%, an amount of talc between 0.5- 5%, an amount of croscarmellose sodium between 2.5-20%, an amount of kollidon CL between 5-20%, an amount of sodium saccharin between 0.5-5%, an amount of sucralose between 12.5-27.5% and an amount of avicel PH 102 between 12.5-27.5% by total weight.

30. The formulation according to claim 29, characterized by comprising; 10% dexketoprofen trometamol, 2% desloratadine, 12% pseudoephedrine HCI, 10% vitamin C, 2% magnesium stearate, 2% talc, 8% croscarmellose sodium, 12% kollidon CL, 2% sodium saccharin, 20% sucralose and 20% avicel PH 102 by total weight.

31. The formulation according to claim 18, characterized by comprising; an amount of dexketoprofen trometamol between 5-20%, an amount of desloratadine between 0.5-5%, an amount of pseudoephedrine HCI between 5-20%, an amount of vitamin C between 5- 20%, an amount of magnesium stearate between 0.5-5%, an amount of talc between 0.5- 5%, an amount of croscarmellose sodium between 5-20%, an amount of kollidon CL between 2.5-20%, an amount of sodium saccharin between 0.5-5%, an amount of sucralose between 12.5-27.5% and an amount of avicel PH 102 between 12.5-27.5% by total weight.

32. The formulation according to claim 31 , characterized by comprising; 10% dexketoprofen trometamol, 2% desloratadine, 12% pseudoephedrine HCI, 10% vitamin C, 2% magnesium stearate, 2% talc, 12% croscarmellose sodium, 8% kollidon CL, 2% sodium saccharin, 20% sucralose and 20% avicel PH 102 by total weight.