MX2008007665A - Solid dispersion comprising an active ingredient having a low melting point and tablet for oral administration comprising same - Google Patents

Abstract

A fused solid dispersion comprising an active ingredient having a melting point of 800C or below and a pharmaceutically acceptable absorbent having a specific surface area ranging from 20 to 400 mVg can be conveniently compressed into a tablet without generating capping and sticking problems, and a tablet comprising said fused solid dispersion can maintain an uniform release rate over a prolonged time when orally administered.

Description

SOLID DISPERSION COMPRISING AN ACTIVE INGREDIENT THAT HAS A LOW FUSION POINT AND TABLET FOR ADMINISTRATION ORAL COMPRISING THE SAME FIELD OF THE INVENTION The present invention relates to a dispersion of molten solids to form tablets by compression, comprising an active ingredient having a low melting point and easily compressed into a tablet, and a tablet for oral administration comprising the same. BACKGROUND OF THE INVENTION When drugs comprising large quantities of an active ingredient having a low melting point, for example, ibuprofen or dexibuprofen (S (+) - ibuprofen) which is a non-steroidal, representative anti-inflammatory drug, are compressed in a tablet without any apparatus such as in cooler, causes a problem, such as a layer and adhesion formation due to the melting of the active ingredient by the heat generated during compression. It is necessary to include a relatively high percentage of the excipient to avoid such problems of layer formation and adhesion. However, in this case, the dosage unit is increased to exhibit an effective concentration in the blood of an active ingredient. Consequently, numerous methods have been reported for effectively compressing such an active ingredient of low melting point into a tablet. For example, WO 92/20334 and DE 3,922,441 describe a pharmaceutical composition comprising a salt of ibuprofen or dexibuprofen, and WO 93/04676 describes a pharmaceutical composition comprising agglomerates of ibuprofen using a suspension comprising ibuprofen or salt thereof, starch, surfactant, water and a solvent. WO 95/01781 describes a method for preparing a bilayer tablet comprising a rapid release layer and a controlled release layer, wherein the rapid release layer comprises ibuprofen, corn starch, cross-linked polyvinylpyrrolidone, carboxymethyl starch, stearate magnesium, while the controlled release layer comprises ibuprofen, mannitol, hydroxypropylmethyl cellulose, talc, magnesium stearate and colloidal silica. However, the above methods are not completely satisfactory in solving the problems, such as layering and adhesion that occur during the compression tablet formation process. BRIEF DESCRIPTION OF THE INVENTION Accordingly, an object of the present invention provides a molten solid dispersion comprising an active ingredient having a low melting point and You can easily compress in a tablet. Another object of the present invention is to provide a tablet for oral administration comprising the same, which is capable of maintaining the uniform release of the drugs over a long period of time. Still another object is to provide a method for the preparation of said tablet. According to one aspect of the present invention, there is provided a molten solid dispersion comprising an active ingredient having a melting point of 80 ° C, or less and a pharmaceutically acceptable absorbent having a specific surface area of from 20 to 400 m2 / g. In accordance with one aspect of the present invention, a controlled release tablet for oral administration comprising the molten solid dispersion is provided. In accordance with another aspect of the present invention, there is provided a multi-layer tablet for oral administration comprising a rapid release layer and a controlled release layer containing the molten solid dispersion. According to yet another aspect of the present invention, there is provided a process for preparing a tablet for oral administration, comprising: a) heating to melt an active ingredient having a melting point of 80 ° C or less and adding a pharmaceutically acceptable absorbent having a specific surface area ranging from 20 to 400 m2 / g thereto to obtain a homogeneous molten solid dispersion; b) cooling, drying and pulverizing the molten solid dispersion obtained in step (a) to obtain granules; and c) adding a release control agent or a pharmaceutically acceptable excipient to the granules obtained in step (b) and compressing the resulting mixture into a tablet. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1: the in vitro release profiles of the fast release tablets prepared in Examples 6 to 10 of the present invention; Fig. 2: the in vitro release profiles of the controlled release tablet prepared in example 11 of the present invention as well as those of the bilayer tablets consisting of the fast release layer and the controlled release layer prepared in the examples 12 and 13 of the present invention, respectively; Fig. 3: the variation in the dissolution profile in of the tablet prepared in Example 12 of the present invention as a function of the rotation speed in the paddlewheel; Fig. 4: the in vitro dissolution profiles of the bilayer tablets consisting of a rapid release layer and a controlled release layer prepared in the examples 14 to 16 of the present invention; and Fig. 5: the variation of the in vitro dissolution profile of the tablet prepared in example 16 of the present invention as a function of the rotation speed of the paddlewheel. DETAILED DESCRIPTION OF THE INVENTION The inventive tablet for oral administration comprises a controlled release tablet comprising a dispersion of molten solid containing an active ingredient and a release controlling agent, a rapid release tablet comprising the molten solid dispersion and a pharmaceutically acceptable excipient, and a multi-layered tablet for oral administration having a controlled release layer formed using ingredients for the controlled release tablet and a fast release layer, using the ingredients for the fast release tablet. Each ingredient of the inventive tablet is described in detail as follows: Molten solid dispersion The molten solid dispersion of the present invention comprises an active ingredient having a melting point of 80 ° C or less and one or more pharmaceutically acceptable absorbers having a specific surface area ranging from 20 to 400 m2 / g. The molten solid dispersion may further comprise an adjuvant for forming tablets selected from the group consisting of a sugar alcohol, a water soluble polymer, an oily base and a mixture thereof. The weight ratio of the active ingredient: the pharmaceutically acceptable absorbent: the adjuvant for tabletting preferably ranges from 1: 0.01-3: 1-2. 1) Active ingredient In the present invention, the active ingredient used in the molten solid dispersion has a melting point of 80 ° C or lower, preferably 50 to 80 ° C and, representative examples of the active ingredient include ibuprofen ( fusion: 75 ~ 77 ° C), dexibuprofen (melting point: 50-54 ° C) or a mixture thereof which are anti-inflammatory drugs useful in the treatment of rheumatoid arthritis. 2) Pharmaceutically Acceptable Absorbent In the present invention, the pharmaceutically acceptable absorbent used in the molten solid dispersion can be any of those conventionally used in the pharmaceutical field, and representative examples of the absorbent include light anhydrous silicic acid, hydrotalcite, magnesium aluminum silicate, aluminum hydroxide, aluminum silicate, aluminum magnesium metasilicate, bentonite, lactose, dextrin, starch, microcrystalline cellulose, hydroxypropylmethyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, ethyl cellulose, methyl cellulose, polyethylene glycol, finely divided crosslinked polyvinyl pyrrolidone or a mixture thereof. Particularly, to avoid problems such as layer and adhesion formation that arise due to melting of the active ingredient by the heat generated during tabletting by compression, a pharmaceutically acceptable absorbent having a specific surface area ranging from 20 to 400 m2 / g, preferably 100 to 300 m2 / g, more preferably 150 to 250 m2 / g. When the specific surface area range of the pharmaceutically acceptable absorbent is less than the lower limit, the problems of layer formation and adhesion still occur. According to the present invention, the weight ratio of the active ingredient and the absorbent can vary from 1: 0.01-3, preferably from 1: 0.1-2. The absorber can be added after the hot melt of the active ingredient. 3) Adjuvant for the formation of tablets (sugar alcohol, water soluble polymer, oil base or mixture thereof). To facilitate granulation after grinding and increase the bonding efficiency of the granules during compression tablet formation by means of decreasing the melt fixation, the inventive fused solid dispersion may further comprise an adjuvant for tabletting. selected from the group consisting of a sugar alcohol, a water soluble polymer, an oil base and a mixture thereof. The weight ratio of the active ingredient: the adjuvant for tabletting preferably 1: 0-2. Representative examples of the sugar alcohol used in the present invention include xylitol, sorbitol, mannitol and mixture thereof, representative examples of the water soluble polymer include hydroxypropylmethyl cellulose, hydroxypropyl cellulose, polyvinyl pyrrolidone, polyethylene glycol, polyoxyethylene oxide, alcohol polyvinyl alcohol and a mixture thereof, and representative examples of the oily base include fatty acid ester of sucrose, glyceryl behenate, glyceryl palmitostearate, glyceryl monooleate, glyceryl monostearate and a mix of them. The molten solid dispersion according to the present invention can be prepared using any conventional mixer, preferably a universal mixer or a heat melt extruder. The method for preparing the molten solid dispersion by the universal mixer or the heat melt extruder is described in detail as follows: a) Preparation of the molten solid dispersion using a universal mixer. An active ingredient is added to a universal mixer preheated to 60 ° C to 100 ° C and melted by heat, followed by homogeneous mixing. A pharmaceutically acceptable absorbent having a specific surface area ranging from 20 to 400 m2 / g was added to the molten drug and the mixture was stirred for 20 to 160 minutes to obtain a homogeneous dispersion. At this time, an adjuvant for tabletting such as a sugar alcohol, a water soluble polymer, and an oily base can also be added to the dispersion. After stopping the heater, the dispersion is stirred at room temperature and the resulting agglomerate is collected, and then dried with cold forced air to obtain a molten solid dispersion comprising the active ingredient. The molten solid dispersion obtained is milled with a high speed mill and the resulting granules are filtered through the mesh No. 14 (1410 μm) to 20 mesh (850 μm), preferably 20 mesh (850 μm) to obtain a molten solid dispersion. b) Preparation of the molten solid dispersion using a heat melt extruder. The active ingredient and the pharmaceutically acceptable absorbent having a specific surface area of 20 to 400 m2 / g were mixed homogeneously, and the mixture placed in a loading hopper is heated to melt in the chamber of a compression screw, followed by the melt extrusion. The obtained agglomerate is mixed homogeneously with mixer-kneader, and the mixtures are filtered through a sieve to obtain a molten solid dispersion having a uniform size. In this process, the length of time that the active ingredient is exposed to heat is trimmed, and a molten solid dispersion having a uniform size distribution can be obtained. Then, a molten solid dispersion having a uniform size distribution can be manufactured by a single process that consumes less time than is conducted by carrying out the ingress, melting and selection of the active ingredients in sequence. Tablet comprising a dispersion of molten solid Various types of tablets such as a controlled release tablet, a fast release tablet and a multilayer tablet can be prepared by optionally adding a pharmaceutically acceptable excipient to the molten solid dispersion and compressing it into a tablet without the use of a cooler The compressed tablet preferably has a hardness that varies in the range from 4 to 16 kp, preferably 8 to 12 kp. A) Controlled release tablet A controlled release tablet comprises the aforementioned molten solid dispersion and a release control agent and can further comprise a pharmaceutically acceptable absorbent. The weight ratio of the molten solid dispersion: the release control agent: the pharmaceutically acceptable excipient varies from 1: 0.01-3: 0-3, and preferably from 1: 0.05-2: 0.01-2. (Al) Agent for control of release The agent for controlling the release to maintain the rate of uniform release over a long period of time can be selected from the group consisting of polyethylene oxide having a molecular weight ranging from 10,000 to 9,000,000, hydroxypropylmethyl cellulose having a molecular weight ranging from 1,000 to 4,000,000, hydroxypropyl cellulose, carboxyvinyl polymer, alcohol poly, xanthan gum, guar gum, locust bean gum, carboxymethyl cellulose and its derivative, methyl cellulose and its derivative, and polyvinyl acetate-povidone copolymer having a molecular weight ranging from 2,000 to 2,000,000. According to the present invention, the weight ratio of the dispersion of molten solid: release control agent varies from 1: 0.01-3, and preferably from 1: 0.05-2. (A-2) Pharmaceutically acceptable excipient In the present invention, to maintain the hardness and dosage form of a tablet, the controlled release tablet may further comprise a pharmaceutically acceptable excipient. The pharmaceutically acceptable excipient used in the present invention can use any conventional used in the pharmaceutical field, and representative examples of the pharmaceutically acceptable excipient include a cross-linked polyvinyl pyrrolidone, a cross-linked sodium carboxymethyl cellulose, carboxymethyl starch, calcium methacrylate copolymer. divinylbenzene, polyvinyl alcohol, lactose, microcrystalline cellulose and cellulose derivative, starch and starch derivative, cyclodextrin and dextrin derivative, pregelatinized starch and its derivative, colloidal silica, magnesium stearate, glyceryl monostearate, sodium stearyl fumarate, Talc and hydrogenated castor oil.

According to the present invention, the weight ratio of the molten solid dispersion: the pharmaceutically acceptable excipient can vary from 1: 0-3, and preferably from 1: 0.01-2. (B) Rapid release tablet In the present invention, a rapid release tablet comprises the aforementioned molten solid dispersion, and the aforementioned pharmaceutically acceptable excipient used in the controlled release tablet. The weight ratio of the molten solid dispersion: the pharmaceutically acceptable excipient can vary from 1: 0.05-3, and preferably from 1: 0.1-2. (6) Multilayer tablet A multi-layer tablet according to the present invention can be prepared by forming a controlled release layer with controlled release tablet ingredients and forming a rapid release layer with fast-release tablet ingredients. to manipulate the release of the active ingredient. The bilayer tablet consists of the rapid release tablet and the controlled release layer can be prepared by subjecting the ingredient for the rapid release layer to a first tablet compression stage, depositing the ingredients for the controlled release layer in the tablet. same, and subjecting the resulting mixture to a second tablet compression step. The tablet compression process of the controlled release layer does not always have to be carried out after tablet formation of the rapid release layer. The tablet compression of the controlled release layer can be carried out first, and then the granules of the rapid release layer are added thereto, followed by compression of the tablet. Also the fast release layer and the controlled release layer can be filled sequentially or inversely, which is compressed into a tablet in a single step once. The multilayer tablet of the present invention can also be prepared as a three layer tablet consisting of the fast release and controlled release layers. When the tablet consisting of the rapid release layer and the controlled release layer comprising the same active ingredient according to the present invention is subjected to in vitro release tests according to the paddle mixer method at 100 rpm ( Korea Pharmacopoeia 8th ed In vitro dissolution tests 2nd method) using 900 ml. of artificial gastric fluid (Korea Pharmacopoeia 8a ed., 2nd solution for the disintegration test,) 85% or more of the active ingredient of the rapid release layer preferably it is released within about 1 hour after starting the test, while the active ingredient of the controlled release layer is released sequentially, preferably in amounts corresponding to 1 to 30% within about 1 hour, from 30 to 70% within approximately 5 hours, and 85% or more within approximately 12 hours after the initiation of the test. The time period of release of the active ingredient from the controlled release layer or the controlled release tablet can be prolonged by controlling the type and amount of excipient used in the controlled release layer. When the in vitro dissolution tests were conducted according to the above method, the active ingredient of the fast release layer is released in the multilayer tablet, preferably in amounts corresponding to 1 to 30% within 1 hour, from 30 to 70% within 6 hours, from 60 to 90% within 12 hours, 80% or more within 24 hours after the initiation of the test. The active ingredient that is rapidly released can allow the concentration of the drug to rapidly reach the effective treatment level while the active ingredient that is released slowly can maintain the effective concentration in plasma for the expected time.

Thus, the pharmaceutically useful tablet according to the present invention is easily prepared without being hindered by problems such as cupping and adhesion during the course of tabletting by compression, which can be effectively implemented in a manufacturing process. big scale. The following examples are intended to further illustrate the present invention without limiting its scope. EXAMPLES Preparation of the dispersion of molten solids Example 1 300 g of dexibuprofen are added to a Universal blender (VERSATILE MIXER (250DM-rrs), DALTON) preheated to 60 ° and allowed to melt, followed by homogeneous mixing. 60 g of light anhydrous silicic acid having a specific surface area of 200 + 25 m2 / g was slowly added thereto and the mixture was stirred slowly for 45 minutes to obtain a homogeneous dispersion (see Table 1). The resulting mixture was cooled to room temperature while stirring to obtain a solid dexibuprofen dispersion agglomeration. The resulting agglomeration was cooled to room temperature with a cold air flow (30 ° C) for about 2 hours, and the resulting product was then milled in a high speed mill. The granules The resulting filtrate was filtered through a No. 20 mesh (850 μm) to obtain a molten solid dispersion. Example 2 A molten solid dispersion was prepared by repeating the procedure of Example 1 except that 110 g of light anhydrous silicic acid having a specific surface area of 200 + 25 m2 / g was used. Example 3 A molten solid dispersion was prepared by repeating the procedure of Example 1 except that 110 g of light anhydrous silicic acid having a specific surface area of 300 + 25 m2 / g was used. Example 4 A dispersion of molten solid was prepared by repeating the procedure of Example 1 except that 300 g of dexibuprofen and 50 g of xylitol were added to the Universal mixer preheated to 95 ° and melted. 60 g of light anhydrous silicic acid having a specific surface area of 200 + 25 m2 / g was slowly added thereto and the mixture was stirred for 45 minutes until a homogeneous dispersion was obtained. Example 5 A dispersion of molten solid was prepared by repeating the procedure of Example 4 except that 20 g of hydroxypropylmethyl cellulose was used in place of 50 g of xylitol.

Table 1 Preparation of the fast-release tablet Example 6 According to the components listed in Table 2, 205 mg of the molten solid dispersion obtained in Example 3 (amount of dexibuprofen: 150 mg per tablet), 10 mg were mixed together. of lactose, 49.7 mg of microcrystalline cellulose, 3.8 mg of cross-linked sodium carboxymethyl cellulose, and 5.1 mg of light anhydrous silicic acid as a pharmaceutically acceptable excipient, for 60 minutes and 11.4 mg of talc were added thereto as a lubricant. The resulting mixture was stirred for 5 minutes and compressed to a hardness of about 8 to 12 kp to obtain a rectangular quick release tablet. Examples 7 to 10 Dispersions of molten solid were prepared by repeating the procedure of Example 6 using the components listed in Table 2 Table 2 Test Example 1: In vitro Dissolution Test of the Rapid Release Tablet The rapid release tablets prepared in Examples 6 to 10 were subjected to the in vitro dissolution test based on the Food and Drug Administration.

Korea (KFDA) and the release guidelines on the drug for oral administration, and the release pattern were analyzed under the following conditions. Dissolution test method Samples: The rapid release tablets prepared in examples 6 to 10. Test solution: The second method of the disintegration test described in the Korea Pharmacopoeia, artificial gastric fluid with pH 6.8, 900 ml, 37 + 0.5 ° C Dosing method: The dissolution test method described in the Korea Pharmacopoeia (the paddlewheel method), rotation speed: 500 rpm.

Table 3 As can be seen from Table 3 and Fig. 1, each of the rapid release tablets prepared in Examples 6 to 10 show a pattern of rapid release of the drug (85% or more within 30 minutes after initiating the drug release), and then, the inventive quick release tablet comprising the dispersion of the molten solid as an active ingredient provides therapeutic effects. Example 11: Preparation of the controlled release tablet A controlled release tablet was prepared by repeating the procedure of Example 6 except that the dispersion of the molten solid, the controlling agent, was used. the release, and the lubricant listed in Table 4. Table 4 Test Example 2: In vitro dissolution test of the controlled release tablet The controlled release tablet prepared in Example 11 was subjected to the in vitro dissolution test under the following conditions, and the results are shown in Table 5 and Fig. 2. Dissolution test method Samples: The controlled release tablet prepared in example 11. Test solution: the second disintegration test method described in Korea Pharmacopoeia, artificial gastric fluid pH 6.8, 900 ml, 37 + 0.5 ° C Dissolution method: the dissolution test method described in Korea Pharmacopoeia (paddle mixer method), rotation speed: 100 rpm. Table 5 As can be seen in Table 5 and Fig. 2, the controlled release tablet prepared from Example 11, slowly released the active ingredient from the controlled release portion over a period of 12 hours. Examples 12 and 13: Preparation of bilayer tablets consisting of the rapid release layer and the controlled release layer (1). The components listed in Table 6 were mixed together and the mixture was subjected to a first tablet compression step at a hardness of about 2 to 3 kp, and then, the controlled release layer was deposited on the tablet. and the resulting material was subjected to a second tablet compression step at a hardness of about 8 to 12 kp to obtain bilayer tablets. Table 6 Test Example 3: In vitro dissolution test of the bilayer tablet (1) The in vitro dissolution tests were conducted using the bilayer tablets prepared in Examples 12 and 13 under the following conditions, and the results are shown in Table 7 and Fig. 2.

Dissolution test method Samples: The bilayer tablets prepared in Examples 12 and 13.

Test solution: The second disintegration test method described in Korea Pharmacopoeia, artificial gastric fluid pH 6.8, 900 ml 37 + 0.5 ° C Dissolution method: The dissolution test method described in Korea Pharmacopoeia (paddle mixer method) ), rotation speed: 100 rpm. Table 7 As can be seen from Table 7 and Fig. 2, each of the bilayer tablets prepared in Examples 12 and 13 showed that all of the active ingredient in the rapid release portion was released, regardless of the amount of the active ingredient, and subsequently, the active ingredient of the controlled release portion was slowly released during a period of 12 hours. Test Example 4: The in vitro dissolution test of the bilayer tablet (1) as a function of the rotation number.

An in vitro dissolution test was conducted using the bilayer tablet prepared in Example 12 under the following conditions and the results are shown in Table 8 and Fig. 3. Dissolution test method Samples: The bilayer tablet was prepared in the Example 12 Test solution: The second disintegration test method described in Korea Pharmacopoeia, artificial gastric fluid pH 6.8, 900 ml 37 + 0.5 ° C. Dissolution method: The dissolution test method described in Korea Pharmacopoeia (paddle mixer method), rotation speed: 50, 100 and 150 rpm. Table 8 As can be seen from Table 8 and Fig. 3, the tablet rapidly released the drug for 1 hour initially, without considering the rotation speed to quickly provide the therapeutic effect, without considering the rotation speed, and subsequently the table showed a pattern of stable release of the drug, adequate to maintain the continuous therapeutic effects. Examples 14 to 16: Preparation of the bilayer tablet (2) The controlled release components listed in Table 9 were subjected to a first tablet compression stage at a hardness of about 2 to 3 kp, and then the rapid release was deposited thereon, and the resulting material was subjected to a second tablet compression step at a hardness of about 8 to 12 kp to obtain bilayer tablets.

Table 9 Test Example 5: In vitro dissolution test of the bilayer tablet (2) The in vitro dissolution tests were conducted using the bilayer tablets prepared in Examples 14 to 16 under the following conditions and the results are shown in Table 10 and Fig. 4. Dissolution test method Samples: The bilayer tablets were prepared in Examples 14 and 16. Test solution: The second disintegration test method described in Korea Pharmacopoeia, fluid Gastric artificial pH 6.8, 900 ml 37 + 0.5 ° C. Dissolution method: The dissolution test method described in Korea Pharmacopoeia (paddle mixer method), rotation speed: 100 rpm. Table 10 As can be seen from Table 10 and Fig. 4, all the active ingredient of the controlled rapid release was released within 1 hour, without considering the amount of the active ingredient, and then, the tablet released the active ingredient continuously for 12 to 24 hours. Test example 6: The in vitro dissolution test of the bilayer tablet (2) as a function of the rotation num In vitro dissolution tests were conducted using the bilayer tablet prepared in Example 16 under the following conditions and the results are shown in Table 11 and Fig. 5. Dissolution test method Sample: The bilayer tablet prepared in Example 16. Test solution: The second disintegration test method described in Korea Pharmacopoeia, artificial gastric fluid pH 6.8, 900 ml 37 + 0.5 ° C. Dissolution method: The dissolution test method described in Korea Pharmacopoeia (paddle mixer method), rotation speed: 50, 100, 150 rpm.

Table 11 As can be seen from Table 11 and Fig. 5, the tablet rapidly released the drug for 1 hour initial to provide therapeutic effects, followed by a stable drug release pattern suitable to continuously maintain the therapeutic effect.

Accordingly, as shown by the result of the dissolution test, the active ingredient of the rapid release portion was released quickly within 1 hour to reach an effective concentration thereof in the blood, rapidly exerting the therapeutic effects. The active ingredient of the controlled release portion can be released slowly over a period of 12 to 24 hours, thus maintaining an effective concentration of the drug in the blood at a constant level for the expected time. While the embodiments of the present invention have been described and illustrated, it is obvious that various changes and modifications may be made therein without departing from the spirit of the present invention which should be limited only by the scope of the appended claims.

Claims (21)

1. CLAIMS 1. A molten solid dispersion, characterized in that it comprises an active ingredient having a melting point of 80 ° C or less and a pharmaceutically acceptable absorbent having a specific surface area ranging from 20 to 400 m2 / g.
2. 2. The molten solid dispersion of claim 1, characterized in that it comprises the active ingredient and the pharmaceutically acceptable absorbent in a weight ratio ranging from 1: 0.01 to 1: 3.
3. 3. The molten solid dispersion of claim 1, characterized in that the active ingredient having a melting point of 80 ° C or lower is ibuprofen, dexibuprofen (S (+) - ibuprofen) or a mixture thereof.
4. 4. The molten solid dispersion of claim 1, characterized in that it further comprises a tabletting aid selected from the group consisting of a sugar alcohol, a water soluble polymer, an oil base or a mixture of the same.
5. 5. The molten solid dispersion of claim 4, characterized in that it comprises the active ingredient and the adjuvant for tabletting in a weight ratio ranging from 1: 0 to 1: 2.
6. 6. The molten solid dispersion of the claim 1, characterized in that the pharmaceutically acceptable absorbent is selected from the group consisting of light anhydrous silicic acid, hydrotalcite, magnesium aluminum silicate, aluminum hydroxide, aluminum silicate, magnesium aluminum metasilicate, bentonite, lactose, dextrin, starch , microcrystalline cellulose, hydroxypropylmethyl cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, ethyl cellulose, methyl cellulose, polyethylene glycol, finely divided crosslinked polyvinyl pyrrolidone and a mixture thereof.
7. 7. The molten solid dispersion of claim 4, characterized in that the sugar alcohol is selected from the group consisting of xylitol, sorbitol, mannitol and a mixture thereof.
8. 8. The molten solid dispersion of claim 4, characterized in that the water soluble polymer is selected from the group consisting of hydroxypropylmethyl cellulose, hydroxypropyl cellulose, polyvinyl pyrrolidone, polyethylene glycol, polyethylene oxide, polyvinyl alcohol and mixtures thereof.
9. 9. The molten solid dispersion of claim 4, characterized in that the oily base is selected from the group of fatty acid ester of sucrose, glyceryl behenate, glyceryl palmito stearate, monooleate of glyceryl, glyceryl monostearate and a mixture thereof.
10. 10. A tablet for oral administration, characterized in that it comprises the dispersion of molten solids according to any of claims 1 to 9.
11. The tablet for oral administration of claim 10, characterized in that it is a controlled release tablet comprises the dispersion of molten solid and a release control agent to slowly release the active ingredient.
12. The tablet for oral administration of claim 11, characterized in that it further comprises a pharmaceutically acceptable excipient.
13. The tablet for oral administration of claim 12, characterized in that it comprises the dispersion of molten solid, the release control agent and the pharmaceutically acceptable excipient in a weight ratio ranging from 1: 0.01-3: 0-3 .
14. The tablet for oral administration of claim 10, characterized in that it is a multilayer tablet consisting of a rapid release layer comprising the dispersion of molten solid and the pharmaceutically acceptable excipient, and a controlled release layer comprising the dispersion of molten solid and a release control agent.
15. 15. The tablet for oral administration of claims 11 or 14, characterized in that the release control agent is selected from the group consisting of polyethylene oxide having a molecular weight varying from 10, 000 to 9,000,000, hydroxypropylmethyl cellulose having a molecular weight ranging from 1,000 to 4,000,000, hydroxypropyl cellulose, carboxyvinyl polymer, polyvinyl alcohol, xanthan gum, guar gum, locust bean gum, carboxymethyl cellulose and its derivative, methyl cellulose and its derivative, and povidone-polyvinylacetate copolymer having a molecular weight ranging from 2,000 to 2,000,000.
16. 16. The tablet for oral administration of claim 14, characterized in that the controlled release layer further comprises a pharmaceutically acceptable excipient. The tablet for oral administration according to any of claims 12, 14 and 16, characterized in that the pharmaceutically acceptable excipient is selected from the group consisting of a cross-linked polyvinyl pyrrolidone, a cross-linked sodium carboxymethyl cellulose, carboxymethyl starch, methacrylate copolymer calcium-divinylbenzene, polyvinyl alcohol, lactose, microcrystalline cellulose and cellulose derivative, starch and its derivative, cyclodextrin and dextrin derivative, pregelatinized starch and its derivative, colloidal silica, magnesium stearate, glyceryl monostearate, sodium stearyl fumarate and hydrogenated castor oil. The tablet for oral administration of claim 14, characterized in that the rapid release layer comprises the dispersion of molten solid and the pharmaceutically acceptable excipient in a weight ratio ranging from 1: 0.05 to 1: 3. The tablet for oral administration of claim 16, characterized in that the controlled release layer comprises the dispersion of molten solid, the release control agent and the pharmaceutically acceptable excipient in a weight ratio ranging from 1: 0.01- 3: 0-3. A process for the preparation of a tablet for oral administration of claim 10, characterized in that it comprises: a) heating to melt an active ingredient having a melting point of 80 ° C or less and adding a pharmaceutically acceptable absorbent having a specific surface area ranging from 20 to 400 m2 / g thereof to obtain a dispersion of homogeneous molten solid; b) cooling, drying and pulverizing the molten solid dispersion obtained in step (a) to obtain granules; Y c) adding a release control agent or a pharmaceutically acceptable excipient to the granules obtained in step (b) and compressing the resulting mixture into a tablet. The process of claim 20, characterized in that it further comprises the step of adding an adjuvant for tabletting selected from the group consisting of a sugar alcohol, a water soluble polymer, an oily base and a mixture of the same, when the pharmaceutically acceptable absorbent is added in step (a).