KR20050019198A - Formulation and manufacturing process solubilized dexibuprofen soft capsules - Google Patents

Abstract

PURPOSE: A formulation comprising solubilized dexibuprofen and a manufacturing process of soft capsules of solubilized dexibuprofen are provided, thereby significantly improving solubility and bioavailability of dexibuprofen as a water-insoluble drug, and increasing the content of dexibuprofen in the soft capsules. CONSTITUTION: The process for manufacturing the soft capsules of solubilized dexibuprofen comprises the steps of: dissolving dexibuprofen and a water-soluble polymer in hydrophilic solubilizing solvent; adding one or more selected from surfactant, diethanolamine and basic amino acid into the dexibuprofen dissolved solution; and filling the formulation of solubilized dexibuprofen into soft capsules, wherein the hydrophilic solubilizing solvent is one or more selected from polyethyleneglycol, propyleneglycol, diethyleneglycolmonoethylether, glycerin and triacetin; the surfactant is one or more selected from hydrogenated castor oil and its derivatives, polysorbate and its derivatives, sodiumlaurylsulfate, and the water-soluble polymer is one or more selected from polyvinylpyrrolidone, hydroxypropylcellulose and hydroxypropylmethylcellulose.

Description

Soft capsule composition of soluble dexibuprofen and a method for producing the same {Formulation and manufacturing process solubilized dexibuprofen soft capsules}

The present invention relates to a composition of a formulation in which a poorly soluble dexibuprofen is solubilized, and a method for preparing the same. Specifically, dexibuprofen which is poorly soluble in water is selected from polyethylene glycol, propylene glycol, diethylene glycol monoethyl ether, and tria. A stable dexibuprofen-containing composition characterized in that it is dissolved in a liquid base such as cetine and solubilized by adding basic amino acids such as sodium lauryl sulfate (SLS), ethanolamines, and arginine, and a soft capsule agent containing the same as an active ingredient. To the formulation.

Dexibuprofen is a nonsteroidal anti-inflammatory drug (NSAIDs) drug mainly used to treat pain and inhibit inflammation. It blocks the synthesis of prostaglandin by non-selectively inhibiting Cyclooxygenase-1 and 2, prostaglandin. A chiral compound of ibuprofen as a known active ingredient that reduces precursor production and has excellent efficacy in treating combustible rheumatoid arthritis and antipyretic analgesics.

Dexibuprofen is a representative soluble powder that has the following structure and is a S (+) isomer of ibuprofen and is a white crystalline powder and hardly soluble in water with a slightly peculiar smell and bitter taste. In order to improve this point and provide adequate bioavailability, much research is being conducted.

Dexibuprofen is an active drug produced by the metabolism of the isomer R (-) ibuprofen, which significantly reduces gastrointestinal toxicity, hepatotoxicity and nephrotoxicity, and the drug expression time is about 30% more than that of conventional ibuprofen. It is reported that it can be shortened and sufficient effect can be exerted even with a smaller amount. Dexibuprofen exhibits more potent arthritis treatment and antipyretic analgesic effects than ibuprofen because dexibuprofen is distributed at high concentrations around inflammatory site joint activity compared to ibuprofen, an R (-) isomer. In the conventional ibuprofen formulation, since R (-) and S (+) ibuprofen were mixed at 50:50, an equivalent effect may be obtained even when only 50% of the conventional formulation is administered. In addition, dexibuprofen is relatively higher in solubility than ibuprofen, so when commercialized, it can exert superior therapeutic effects than R (-) ibuprofen, thereby improving medication compliance for long-term patients. Dexibuprofen-containing formulations are currently developed and marketed in the form of tablets, but in the case of tablets in pharmaceutical formulations, the oral administration should be preferentially degraded, and the drug mixed with excipients and the like dissolved in digestive or bodily fluids. It requires several steps to be absorbed. Therefore, in the case of tablets, compared to the case of taking a drug that is already dissolved, such as a liquid formulation or soft capsules, the effect expression time is bound to be delayed. Therefore, the present inventors have been researching a formulation that can supplement the disadvantages of the conventional tablets and resolve the rejection of the therapeutic drug, and succeeded in developing a solubilized soft capsule formulation that can maximize the therapeutic effect as in the present invention. It was.

In other words, the present invention relates to a composition of a formulation in which solubilized dexibuprofen is poorly soluble, and a method for preparing the same. Specifically, dexibuprofen insoluble in water is selected from polyethylene glycol, propylene glycol, diethylene glycol monoethyl ether, and tria. Dexibuprofen-containing composition characterized in that it is dissolved in a liquid base such as cetine and solubilized by the addition of basic amino acids such as sodium lauryl sulfate (SLS), ethanolamines, arginine, etc. and a soft capsule formulation containing the same as an active ingredient It is about.

In general, in order for a drug to be absorbed into the human body and exhibit high pharmacological activity in vivo, it must first be eluted rapidly. The dissolution rate of the drug determines the rate of absorption in the body and is a significant indicator of drug concentration in the blood. It depends on the solubility. However, since the solubility of the drug is poorly soluble in water, various methods have been studied to improve the solubility.

Typical examples include the use of cosolvents, the addition of counterions to poorly soluble materials to form salts of acids or bases, and the combination of polymer compounds or ligands to form soluble complexes. In addition, there is a method of increasing the solubility by using a surfactant and a cosolvent as a soft capsule agent in a solubilized solution solubilized.

The soft capsule formulation is divided into two types according to the prescription and preparation method of the internal medicine. The first is generally known methods such as vegetable oils such as soybean oil, palm oil, sunflower seed oil, sesame oil, perilla oil, olive oil, and oil-based oils such as medium-chain fatty acid triglycerides. It is a method of suspending the active ingredient drug using a suspending agent such as beeswax in the base having the property of. This method may delay the dissolution of the drug and should be carefully considered.

Second is a method of solubilizing or suspending the main ingredient drug in a liquid base such as polyethylene glycol, propylene glycol, diethylene glycol monoethyl ether, triacetin and the like. In the present invention, when dexibuprofen is used as a soft capsule formulation to improve the dissolution rate, it is difficult to expect the dissolution rate as a method of suspending it in a substrate having an oily property, which is the first method. Also, among the methods using the water-soluble base, which is the second method, dissolution of dexibuprofen with a base alone such as polyethylene glycol 400 may improve the dissolution rate than the suspension method of the above-mentioned oily base. Precipitation may occur and dissolution rate will not be significantly improved. In addition, the cause of the decrease in content may occur, it may be impossible to ensure the stability of the product.

U.S. Patent No. 5,141,961 discloses an ethanol-containing liquid formulation in which ibuprofen is solubilized using ethanol, polyethylene glycol and polyvinylpyrrolidone, and U.S. Patent No. 5,071,643 relates to an ionizable pharmaceutical solvent system, A method for solubilizing ibuprofen using a new solvent system of polyethylene glycol, polyvinylpyrrolidone and water has been disclosed, but this method is also not recommended as it may affect softening and curing of soft capsules. US Patent No. 5,141,961 Since the composition disclosed in the above is an ethanol liquid composition, it is pointed out as a problem that the stability is lowered during long-term preservation, that is, the contents are precipitated due to the change in ethanol content. . Therefore, if possible, the method of solubilizing the drug without using purified water or ethanol will be able to produce the soft capsule more effectively.

Currently, most formulations of dexibuprofen have been developed as tablets, and soft capsules have not been developed or marketed yet. However, in the case of ibuprofen, soft capsules containing a low content of ibuprofen are commercially available, but this has a disadvantage in that at least two capsules should be taken in a single dose. In the case of tablets, because dexibubupropene is poorly soluble, the dissolution rate and dissolution rate are not excellent, so the expression of the drug cannot be properly expressed due to low bioabsorption rate and bioavailability. In addition, when dexibuprofen has a low melting point and is formulated into tablets, it is often difficult to dissolve during mixing or tableting, which makes it difficult to formulate. Especially, the tablet is easily softened at high humidity and high temperature. Much attention is required because it may appear.

Therefore, the technical problem to be achieved by the present invention is to further improve the dissolution rate and bio-absorption rate of the tablet as described above, to develop a high-dose dosage form that expresses the expression of the drug to the patient as quickly as possible, The formulation was developed with a high content soft capsule with high human absorption rate and bioabsorption rate. However, even in the case of a soft capsule formulation, precipitation occurs even when a large amount of poorly soluble dexibuprofen is dissolved in a hydrophilic liquid base such as polyethylene glycol, propylene glycol, diethylene glycol monoethyl ether, triacetin, or a mixed solution. It is difficult to significantly improve the dissolution rate and dissolution rate of the drug. Therefore, the solubility of dexibuprofen is added by adding sodium lauryl sulfate (SLS), ethanolamines and basic amino acids in order to soften the dexibuprofen by content ranging from low content to high content to improve dissolution rate and stability. To further increase the bioavailability can greatly improve the stability of the dexibuprofen when stored, and to fill the soft capsules by the method of designing a soft capsule formulation to form a formulation that can greatly improve the dissolution rate Developed to complete the present invention.

An object of the present invention is 20 to 50 parts by weight of dexibuprofen alone to 30 to 80 parts by weight of one or more mixtures selected from polyethylene glycol, propylene glycol, diethylene glycol monoethyl ether, triacetin, etc. Or 20 to 50 parts by weight of dexibuprofen and a water-soluble polymer compound are mixed and dissolved, and then selected from 0.1 to 3 parts by weight of sodium lauryl sulfate, 1 to 30 parts by weight of ethanolamines, or 0.1 to 30 parts by weight of arginine. It is to provide a method for solubilizing dexibuprofen characterized by mixing two or more kinds.

Another object of the present invention is 20 to 50 parts by weight of dexibuprofen to 30 to 80 parts by weight of one or more mixtures selected from polyethylene glycol, propylene glycol, diethylene glycol monoethyl ether, triacetin, etc. Or 20 to 50 parts by weight of dexibuprofen and 2 to 15 parts by weight of polyvinylpyrrolidone are dissolved and dissolved, and then 0.1 to 3 parts by weight of sodium lauryl sulfate, 1 to 30 parts by weight of diethanolamine, or 0.1 to arginine. It is to provide a solubilized liquid composition of a poorly soluble drug and a soft capsule containing the same, characterized in that 1 to 2 or more selected from 30 parts by weight.

In the present invention, dexibuprofen can be solubilized to 1 to 55 parts by weight, and for expression of the drug effect, solubilization to 1 to 45 parts by weight depending on the amount of dexibuprofen was used to secure dissolution and content stability. Herein, the solubilizing agent of dexibuprofen used one or two or more mixtures selected from polyethylene glycol 400, propylene glycol, diethylene glycol monoethyl ether, triacetin, sodium lauryl sulfate, diethanolamine, and arginine. One or more mixtures selected from polyethylene glycol 400 or propylene glycol, diethylene glycol monoethyl ether, triacetin and the like were used as the main dissolving agent. In this case, the polyethylene glycol 400 is used in an amount of 30 to 80 parts by weight, more preferably 40 to 60 parts by weight.

In addition, since dexibuprofen is poorly soluble in water, solubility is poor, and as a method for improving solubility, a method of making a soluble complex by combining a water-soluble polymer compound is used. Examples of the water-soluble high molecular compound include polyvinylpyrrolidone, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, etc. Here, polyvinylpyrrolidone is used, and the amount thereof is preferably 2 to 15 parts by weight.

Also, sodium lauryl sulfate is 0.1 to 3 parts by weight, more preferably 0.5 to 2 parts by weight, diethanolamine is 1 to 30 parts by weight, more preferably 2 to 10 parts by weight, arginine is 0.1 to 30 parts by weight, More preferably, 0.5 to 10 parts by weight is used. This is because solubilization is impossible below the lower limit of the range of use of each component, and if the upper limit is exceeded, the size of the formulation may increase, which may lower the commerciality.

In the present invention, a method of preparing a drug substance using the above components is first mixed with polyethylene glycol 400, dexibuprofen or polyvinylpyrrolidone K-30 thereto, and then heated and mixed at a temperature of about 55 to 95 ° C. After dissolution, SLS, diethanolamine, and arginine are added to confirm dissolution. The completely dissolved drug is cooled to room temperature with gentle stirring, and then bubbles are removed using a vacuum pump to obtain a solubilized content.

The soft capsule coating in the present invention is produced by a conventional manufacturing method by soft gel prescription of gelatin and plasticizer generally used. In addition, the solubilized soft capsule containing the dexibuprofen of the present invention is molded into a conventional filling method using a rotary automatic charger, which is currently a general method, and then subjected to drying and sorting to a prototype.

In addition, the soft capsules prepared according to the present invention were excellent in dissolution and content stability, and as a result of measuring changes over time for 6 months under accelerated conditions and room temperature conditions, there was almost no change in content and properties over time. The dissolution rate was superior to that of the tablet. Therefore, the effect of the present invention is to invent a formulation having excellent dissolution rate and high stability compared to the conventional formulation.

Hereinafter, the present invention will be described in more detail with reference to Examples and Comparative Examples. However, these examples do not limit the scope of the present invention.

<Example 1>

600 g of polyethylene glycol 400 was mixed with 300 g of dexibuprofen and 60 g of polyvinylpyrrolidone K-30, followed by heating to complete dissolution at a temperature of about 95 ° C. After confirming that the solution is completely transparent, the temperature is cooled to room temperature and bubbles are removed using a vacuum pump to obtain 960 g of the solubilized content of dexibuprofen.

<Example 2>

600 g of polyethylene glycol 400 was mixed with 300 g of dexibuprofen and 60 g of polyvinylpyrrolidone K-30, and then dissolved by heating at 95 ° C. and 5 g of sodium lauryl sulfate was completely dissolved. After confirming that it has dissolved and become completely transparent, the temperature is cooled to room temperature and bubbles are removed using a vacuum pump to obtain 965 g of the solubilized content of dexibuprofen.

<Example 3>

After mixing 300 g of dexibuprofen with 695 g of polyethylene glycol 400, the mixture is completely mixed by adding 5 g of sodium lauryl sulfate after heating and dissolving at 95 ° C. After confirming that it has dissolved and become completely transparent, the temperature is cooled to room temperature and bubbles are removed using a vacuum pump to obtain 1000 g of the solubilized content of dexibuprofen.

<Example 4>

300 g of dexibuprofen and 7 g of meglumine are mixed with 610 g of polyethylene glycol 400, followed by heating and dissolving at 95 ° C., followed by 80 g of diethanolamine and 3 g of sodium lauryl sulfate. After confirming that it has dissolved and become completely transparent, the temperature is cooled to room temperature and bubbles are removed using a vacuum pump to obtain 1000 g of the solubilized content of dexibuprofen.

Example 5

396 g of polyethylene glycol 400 was mixed with 300 g of dexpropene and 4 g of sodium lauryl sulfate, and then dissolved in warming at 67 ° C. and confirmed to be completely transparent. Then, the temperature was cooled to room temperature and bubbles were removed using a vacuum pump to dexibuprofen. 700 g of solubilized content of is obtained.

<Example 6>

600 g of propylene glycol is mixed with 300 g of dexibuprofen, and then dissolved by heating at 80 ° C., and then thoroughly mixed by adding 4 g of sodium lauryl sulfate. After confirming that it is dissolved and completely transparent, the temperature is cooled to room temperature and bubbles are removed using a vacuum pump to obtain 904 g of the solubilized content of dexibuprofen.

<Example 7>

After mixing 300 g of dexibuprofen with 400 g of propylene glycol, the mixture is completely mixed by adding 4 g of sodium lauryl sulfate after dissolving warm at 80 ° C. After confirming that the solution is completely transparent, the temperature is cooled to room temperature and bubbles are removed using a vacuum pump to obtain 704 g of the solubilized content of dexibuprofen.

<Example 8>

400 g of triacetin is mixed with 300 g of dexibuprofen, and then dissolved by heating at 80 ° C., and 4 g of sodium lauryl sulfate is added to mix thoroughly. After confirming that the solution has become completely transparent, the temperature is cooled to room temperature and bubbles are removed using a vacuum pump to obtain 904 g of dexibuprofen solubilized contents.

Example 9

400 g of diethylene glycol monoethyl ether is mixed with 300 g of dexibuprofen, and then dissolved by heating at 70 ° C., followed by adding 4 g of sodium lauryl sulfate to completely mix. After confirming that the solution is completely transparent, the temperature is cooled to room temperature and bubbles are removed using a vacuum pump to obtain 704 g of the solubilized content of dexibuprofen.

Comparative Example 1

600 g of polyethylene glycol 400 was mixed with 300 g of dexibuprofen, and then warmed to completely dissolve at a temperature of about 95 ° C. After confirming that it has dissolved and become completely transparent, the temperature is cooled to room temperature and bubbles are removed using a vacuum pump to obtain 900 g of the solubilized content of dexibuprofen.

Comparative Example 2

300 g of dexibuprofen, 185 g of microcrystalline cellulose PH102, 10 g of starch, and 3 g of silicon dioxide are mixed, followed by final mixing of 2 g of magnesium stearate to obtain a dexibuprofen tablet.

<Production of Film>

Soft capsule film in the present invention is a general soft capsule containing a known gelatin, a plasticizer as a prescription for producing a soft capsule, gelatin 186 mg per 1 capsule (263 mg), glycerin 75.3 mg, ethylvanillin 1.1 mg, paraoxybenzoic acid methyl 0.52 mg, para It is prepared by a conventional preparation method containing 0.08 mg of propyl oxycyanate.

The soft capsule production of the dexibuprofen solubilizing agent of the present invention is molded into Oblong # 6 by a conventional filling method using a rotary automatic filling machine, which is generally used, and then subjected to drying and sorting to produce a prototype.

Experimental Example 1 Dissolution Rate Test and Comparative Evaluation

The comparative evaluation of the dissolution rate was carried out with a soft capsule and a dexibuprofen tablet solubilized dexibuprofen drug in water-soluble base, the test results are shown in Table 1.

The dissolution test of dexibuprofen soft capsule was tested according to the dissolution test method of the desibuprofen tablet set by the company.

 ▶ Temperature: 37 ℃

 Dissolution method: Paddle method

 Stirring Speed: 50rpm

 Analysis method: Eluate was taken at 5, 10, 15, 30, 45, and 60 minutes after the start of the dissolution test. The solution was filtered using a 0.45 µm membrane filter as a sample solution. Absorbance was measured at the wavelength.

Dissolution time (minutes) Dissolution rate (%) Comparative Example 1 Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Example 7 Example 8 Example 9 Comparative Example 2 5 1.6 2.1 2.7 3.1 2.2 4.3 2.3 1.4 1.8 2.9 1.1 10 13.2 18.3 21.2 23.7 21.4 19.2 17.1 16.3 18.3 25.3 12.3 15 58.3 69.4 74.3 78.1 76.3 73.4 74.2 74.3 72.6 79.4 68.5 30 79.6 88.6 88.7 97.0 93.6 98.8 92.8 91.6 93.3 95.5 85.1 45 86.3 94.3 93.2 101.3 99.9 100.2 98.2 98.3 98.7 100.8 88.7 60 96.2 99.1 98.8 100.7 100.1 100.4 100.7 100.4 99.0 100.5 96.5

TABLE 1 Dissolution rate test results of dexibuprofen formulation (pH 7.2 phosphate buffer)

As can be seen in Table 1, the dexibuprofen formulation solubilized by the method of the present invention is a soft capsule formulation that improves the dissolution rate of the conventional formulation, thereby increasing the dissolution rate of dexibuprofen, thereby greatly improving the absorption rate of the human body. There is a characteristic that can be greatly increased.

Experimental Example 2 Comparative Evaluation of Stability with Time

The comparative stability evaluation of the soft capsules in the present invention was carried out for 6 months at room temperature and 40 ℃ accelerated conditions with Examples 1 to 9 and Comparative Example 1 of the present invention and the test results are shown in Table 3 and same.

Table 2 Results of stability test of dexibuprofen formulation (content test, acceleration condition)

Elapsed time (months) content(%) Comparative Example 1 Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Example 7 Example 8 Example 9 Comparative Example 2 0 100.3 100.4 100.5 100.1 100.2 100.1 100.8 100.6 100.0 100.4 100.3 One 99.7 98.7 99.3 99.9 100.1 99.9 98.3 96.4 97.1 100.0 100.1 2 98.3 97.4 96.3 100.3 100.0 99.9 97.3 97.1 95.5 100.2 99.9 4 96.2 96.6 95.2 100.3 100.2 100.3 96.4 95.3 92.3 99.3 100.1 6 95.4 94.3 94.8 100.2 100.1 100.1 95.1 95.0 91.1 99.4 100.1

As shown in Table 2, the soft capsule prepared in the same manner as in the present invention did not cause a decrease in content.

TABLE 3 Results of stability test of dexibuprofen formulation

division 6 months accelerated condition Comparative Example 1 Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Example 7 Example 8 Example 9 Comparative Example 2 Change of appearance - - - - - - - - - - - Precipitation + - - - - - - - - - -

[Precipitation (Appearance): Very much ++++ Many +++ Normal ++ A little + None-]

As shown in Table 3, the soft capsule prepared in the same manner as in the present invention did not generate browning or precipitation.

According to the present invention, a solubilization method and a composition and a solubilizing composition which can greatly improve the dissolution rate by completely solubilizing dexibuprofen in a polyethylene glycol, polyvinylpyrrolidone, sodium lauryl sulfate, diethanolamine, and basic amino acid mixture. With the completion of the invention regarding the formulation containing soft capsules, new formulations of products containing high content of low-capacity soft capsule formulations and improving the dissolution rate and absorption in the body of poorly soluble drugs that existing similar formulations have not solved will be developed. Can be.

Claims (12)

Dexibuprofen is dissolved in a hydrophilic solubilizing solvent, and then 1 to 2 or more selected from surfactants, diethanolamine or basic amino acids are added to solubilize the dexibuprofen. Dexibuprofen and a water-soluble high molecular compound by mixing and dissolving in a hydrophilic solubilizing solvent, and then, 1 to 2 or more selected from surfactants, diethanolamine or basic amino acid is added to solubilize the dexibuprofen prepared Way. The method according to claim 1 or 2, As the hydrophilic solubilizing solvent, one or two or more selected from polyethylene glycol, propylene glycol, diethylene glycol monoethyl ether, glycerin, and triacetin. The method according to claim 1 or 2, The surfactant is a production method using at least one selected from hydrogenated castor oil and derivatives thereof, polysorbate and derivatives thereof, sodium lauryl sulfate. The method of claim 2, The water-soluble high molecular compound is a manufacturing method using one or two or more selected from polyvinylpyrrolidone, hydroxypropyl cellulose, hydroxypropyl methyl cellulose. 20 to 50 parts by weight of dexibuprofen is dissolved by mixing 30 to 80 parts by weight of polyethylene glycol, and then 0.5 to 2 parts by weight of sodium lauryl sulfate, 2 to 10 parts by weight of diethanolamine, or 0.5 to 10 parts by weight of arginine A solubilizing composition in which one or two or more selected from the above is mixed under heating to solubilize dexibuprofen. 20 to 50 parts by weight of dexibuprofen and 2 to 15 parts by weight of polyvinylpyrrolidone are dissolved by mixing 30 to 80 parts by weight of polyethylene glycol, and then 0.5 to 2 parts by weight of sodium lauryl sulfate and 2 to 10 of diethanolamine. A solubilizing composition in which dexibuprofen is solubilized by mixing one to two or more selected from parts by weight or 0.5 to 10 parts by weight of arginine under heating. The method according to claim 6 or 7, Polyethylene glycol solubilization composition characterized in that using polyethylene glycol 300 or 400. The method of claim 7, wherein The solubilization composition of polyvinylpyrrolidone is characterized by using one or two or more selected from 12, 15, 17, 25, 30, 60, 90 and 120 K-value. 30 to 80 parts by weight of polyethylene glycol, 20 to 50 parts by weight of dexibuprofen, dissolved by mixing with a soft capsule core total weight, 0.5 to 2 parts by weight of sodium lauryl sulfate, 2 to 10 parts by weight of diethanolamine or A soft capsule, characterized in that the soft capsule is filled with dexibuprofen prepared by mixing solubilizing one or two or more selected from 0.5 to 10 parts by weight of arginine. 20 to 50 parts by weight of dexibuprofen and 2 to 15 parts by weight of polyvinylpyrrolidone were dissolved in 30 to 80 parts by weight of polyethylene glycol, based on the total weight of the soft capsule core, and dissolved in sodium lauryl sulfate 0.5 to 2 parts by weight. A soft capsule, characterized in that the soft capsule is filled with dexibuprofen prepared by mixing and solubilizing one or two or more selected from 2 to 10 parts by weight of diethanolamine or 0.5 to 10 parts by weight of arginine. The method of claim 10 or 11, A soft capsule containing dexibuprofen in a high content and transparent.