JP2022184789A - Small-sized tablet containing sulfamethoxazole and trimethoprim - Google Patents

Abstract

To provide a novel tablet that is easily ingested by a child or elderly patient, and has sulfamethoxazole and trimethoprim as active ingredients.SOLUTION: Provided is a small-sized tablet containing 100 mg of sulfamethoxazole, 20 mg of trimethoprim, and 1 to 3 wt.% of a sweetening agent having high sweetness.SELECTED DRAWING: None

Description

There is an application for exception to loss of novelty

The present invention relates to mini-tablets containing sulfamethoxazole and trimethoprim.

A combination drug containing sulfamethoxazole and trimethoprim as active ingredients (hereinafter referred to as "ST combination drug") is used for the treatment and prevention of urinary tract infections and pneumocystis pneumonia.

Non-Patent Document 1 describes the composition of a commercially available ST mixture. "Bacta® Combination Tablets" contains sulfamethoxazole, trimethoprim, carmellose calcium, hydroxypropylcellulose, magnesium stearate, but no sweetener. On the other hand, "Bacta (registered trademark) combination granules" contain sulfamethoxazole, trimethoprim, carmellose calcium, hydroxypropylcellulose, corn starch, sucrose, hydrous silicon dioxide, and sucrose as a sweetener. there is

ST mixtures are also known as oral preparations for poultry and livestock. was commercially available. This oral preparation is expected to be effective for animals other than pigs, such as chickens. Possibly because it does not suit the tastes of chickens, the amount of water consumed by chickens decreases, leading to a decrease in drug efficacy and a decrease in the rate of weight gain. Patent Document 1 describes a poultry formulation containing sulfamethoxazole and trimethoprim that does not cause a decrease in water intake. Sodium glutamate, sucrose, brown sugar, fructose, powdered coffee, powdered black tea food, powdered green tea powder, powdered maltose food, powdered green tea food, powdered cocoa food, powdered soy sauce, L-ascorbic acid, etc., is added to an aqueous solution of sol and trimethoprim as seasonings. is described to be blended.

JP-A-6-263637

"Bacta (registered trademark) Combination Tablets/Bacta (registered trademark) Combination Granules" package insert (revised March 2021 (2nd edition))

For children and elderly patients, commercially available ST combination tablets (eg, Bacta® combination tablets) are difficult to swallow due to their large diameter of about 11 mm. In addition, since the active ingredients, sulfamethoxazole and trimethoprim, have a bitter taste, especially children often resist taking them. Therefore, there has been a demand for improved tablets for the purpose of improving compliance with medication.

The inventors of the present invention have made intensive studies to solve the above problems, and found that the amounts of sulfamethoxazole and trimethoprim are reduced to about 1/4 of the conventional amounts, and about 1 to about 3% of the high-intensity sweetener. By blending, without impairing the properties required as a tablet, it was found that the tablet can be downsized and the bitterness can be suppressed, and the present invention has been completed.

That is, the present invention
(1) 90.0-110.0 mg of sulfamethoxazole, 18.0-22.0 mg of trimethoprim and 1-3% by weight of a high-intensity sweetener, with a tablet volume of 94-119 mm ³ some pills,
(2) The description of (1), wherein the high-intensity sweetener is one or more selected from the group consisting of sucralose, stevia, aspartame, acesulfame potassium, glycyrrhizic acid (dipotassium glycyrrhizinate), thaumatin, advantame and saccharin. tablets of
(3) the tablet according to (2), wherein the high-intensity sweetener is sucralose;
(4) the tablet according to any one of (1) to (3), wherein the amount of sulfamethoxazole is about 100 mg and the amount of trimethoprim is about 20 mg;
(5) The tablet according to any one of (1) to (4), wherein the amount of high-intensity sweetener is 2% by weight;
(6) The tablet according to any one of (1) to (5), further containing at least one of hydroxypropylcellulose and carmellose calcium,
(7) containing 77.9 to 79.5% by weight of sulfamethoxazole and 15.5 to 15.9% by weight of trimethoprim relative to the tablet mass, and having a tablet thickness of 3.72 to 4.63 mm; a tablet having a tablet mass of 117.9-151.9 mg and a tablet density of 1.07-1.34 mg/ ^mm3 ;
(8) The tablet according to (7), which further contains 1 to 3% by weight of a high-intensity sweetener,
(9) The tablet according to (7) or (8), which has a tablet thickness of 4.26 to 4.46 mm,
(10) The tablet according to any one of (7) to (9), which has a tablet mass of 123.2 to 130.8 mg,
(11) The tablet according to any one of (7) to (10), which has a tablet density of 1.07 to 1.20 mg/mm ³ ,
(12) The tablet according to any one of (7) to (11), wherein the tablet volume is 94-119 mm ³ ;
(13) The tablet according to any one of (7) to (12), wherein the high-intensity sweetener is sucralose,
(14) The tablet according to any one of (7) to (13), wherein the amount of sulfamethoxazole is 90.0-110.0 mg and the amount of trimethoprim is 18.0-22.0 mg,
(15) The tablet according to (14), wherein the amount of sulfamethoxazole is about 100 mg and the amount of trimethoprim is about 20 mg. The tablet according to any one of (7) to (15), which has a friability of 1.0% or less,
(17) The tablet according to any one of (7) to (16), wherein the disintegration time in the disintegration test method specified in the 17th revision of the Japanese Pharmacopoeia is within 30 minutes,
(18) The tablet of (16) or (17), wherein the amount of sucralose is 1-2% by weight,
(19) A tablet according to (16) or (17), wherein the amount of sucralose is 2% by weight.

The tablet of the present invention is easy for children and elderly patients to take, and contributes to improved patient compliance.

The tablet of the present invention (hereinafter referred to as "this tablet") is a round tablet and contains sulfamethoxazole and trimethoprim as active ingredients at a weight ratio of 100:20.
In one embodiment, the tablet contains 100 mg sulfamethoxazole and 20 mg trimethoprim per tablet. This is 1/4 of the amount contained in the conventional ST combination tablet (Bacta (registered trademark) combination tablet), and by taking 4 tablets of this tablet, the dose is equivalent to 1 conventional combination tablet. be able to.
In this case, "100 mg" described above as the weight of sulfamethoxazole and "20 mg" described above as the weight of trimethoprim are both labeled amounts and standard methods used for measurement or quantification. Includes any measured value within the error range due to Such ranges are typically ±10%, more typically ±5% of the stated numerical value. Therefore, the above "100 mg of sulfamethoxazole" indicates that sulfamethoxazole is contained in the range of 90.0 to 110.0 mg, preferably 95.0 to 105.0 mg, The above "20 mg of trimethoprim" indicates that the content of trimethoprim is in the range of 18.0 to 22.0 mg, preferably in the range of 19.0 to 21.0 mg.

The tablets contain 1-3% by weight of a high intensity sweetener. As used herein, a high-intensity sweetener means a natural or synthetic sweetener that exhibits sweetness in a trace amount. Examples of high intensity sweeteners include sucralose, stevia, aspartame, acesulfame potassium, glycyrrhizic acid (dipotassium glycyrrhizinate), thaumatin, advantame and saccharin. Those listed in Pharmaceutical Excipients Standards or Food Additives Compendium can be used. Sucralose is particularly preferred.

The amount of sucralose in the tablet is 1-3 wt%, preferably 1-2 wt% or 2-3 wt%, more preferably about 2 wt%.

As used herein, the term "about" means that the numerical values set forth include any value within a statistically meaningful range. Such ranges are typically ±10%, more typically ±5% of the stated numerical value. Such ranges may be within experimental error by standard methods used for measurement or quantification. Variations encompassed by the term "about" depend on the experimentation or product manufacturing conditions being practiced, and are readily discernible by those of ordinary skill in the art.

The tablet may contain a disintegrant, and a disintegrant listed in the Japanese Pharmacopoeia, Japanese Non-Pharmacopoeia Pharmaceutical Standards, Pharmaceutical Excipients Standards, or Food Additives Codex can be used.
The amount of the disintegrant in the tablet is 0.1 to 4.4 parts by weight, preferably 1.5 to 2.0 parts by weight, more preferably 1.5 to 2.0 parts by weight, per 120 parts by weight of the active ingredients (sulfamethoxazole and trimethoprim). about 1.75 parts by weight.
Examples of disintegrants include cellulose-based disintegrants, starch-based disintegrants, vinyl-based disintegrants, and magnesium aluminometasilicate.
Cellulosic disintegrants include carmellose, carmellose calcium, carmellose sodium, hydroxypropylcellulose, low-substituted hydroxypropylcellulose, croscarmellose sodium (Ac-Di-Sol), crystalline cellulose, powdered cellulose and the like.
Starch-based disintegrants include partially pregelatinized starch, potato starch, corn starch, hydroxypropyl starch, sodium carboxymethylstarch, sodium low-substituted carboxymethylstarch, sodium starch glycolate, pregelatinized starch, starch and the like.
Examples of vinyl disintegrants include crospovidone and polyvinyl alcohol.
Carmellose calcium is preferred. Two or more of these disintegrants may be mixed in an appropriate ratio and used.

The tablet may contain a binder, and binders listed in the Japanese Pharmacopoeia, Japanese Non-Pharmacopoeia Pharmaceutical Standards, Pharmaceutical Excipients Standards, Food Additives Codex, etc. can be used.
The amount of the binder in the tablet is 1.3 to 3.8 parts by weight, preferably 2.0 to 3.0 parts by weight, more than 120 parts by weight of the active ingredients (sulfamethoxazole and trimethoprim). Preferably about 2.5 parts by weight.
Examples of binders include cellulose-based binders, starch-based binders, vinyl-based binders, polyols, gum arabic, gum arabic powder, gum arabic powder, alginic acid, sodium alginate, sucrose, gelatin, dextrin, pullulan, and tragacanth. , tragacanth powder, xanthan gum, pectin, sodium polyacrylate, agar, oak powder, guar gum, light anhydrous silicic acid, hydrogenated oil, and the like.
Cellulosic binders include carboxymethylcellulose (carmellose, CMC), carboxymethylcellulose sodium (carmellose sodium), hydroxyethylcellulose (HEC), hydroxypropylcellulose (HPC), hydroxypropylmethylcellulose (hypromellose) (HPMC), methylcellulose (MC ), crystalline cellulose, microcrystalline cellulose, ethyl cellulose, crystalline cellulose/carmellose sodium, carmellose calcium, powdered cellulose, low-substituted hydroxypropyl cellulose, and the like.
Starch binders include starch, pregelatinized starch, partially pregelatinized starch, potato starch, wheat starch, rice starch, perforated starch, corn starch, hydroxypropyl starch, sodium starch glycolate (sodium carboxymethyl starch), and the like. mentioned.
Vinyl-based binders include polyvinyl alcohol (PVA), polyvinylpyrrolidone (povidone) (PVP), carboxyvinyl polymer, copolyvidone, and the like.
Polyols include macrogol (polyethylene glycol) 200, macrogol 300, macrogol 400, macrogol 600, macrogol 1000, macrogol 1500, macrogol 1540, macrogol 4000, macrogol 6000, macrogol 20000, glycerin, polyoxyethylene [105] polyoxypropylene [5] glycol, propylene glycol and the like.
Hydroxypropyl cellulose (HPC) is preferred. Two or more of these binders may be mixed in an appropriate ratio and used.

The tablet may contain a lubricant, and a lubricant listed in the Japanese Pharmacopoeia, Japanese Non-Pharmacopoeia Pharmaceutical Standards, Pharmaceutical Excipients Standards, Food Additives Codex, etc. can be used. .
The amount of the lubricant in the tablet is 0.1 to 0.9 parts by weight, preferably 0.2 to 0.3 parts by weight, per 120 parts by weight of the active ingredients (sulfamethoxazole and trimethoprim). More preferably about 0.25 parts by weight.
Lubricants include, for example, stearic acid and metal stearates, inorganic lubricants, hydrophobic lubricants, hydrophilic lubricants, sodium stearyl fumarate and the like.
Stearic acid and stearic acid metal salts include magnesium stearate, calcium stearate, stearic acid, stearyl alcohol, polyoxyl 40 stearate and the like.
Inorganic lubricants include talc, light anhydrous silicic acid, hydrated silicon dioxide, magnesium carbonate, precipitated calcium carbonate, dried aluminum hydroxide gel, magnesium aluminometasilicate, magnesium silicate, synthetic aluminum silicate, magnesium oxide, Magnesium sulfate etc. are mentioned.
Hydrophobic lubricants include cacao butter, carnauba wax, glycerin fatty acid ester, hydrogenated oil, white beeswax, hydrogenated soybean oil, beeswax, cetanol, sodium laurate and the like.
Hydrophilic lubricants include sucrose fatty acid esters, polyethylene glycol (macrogol) and the like.
Magnesium stearate is preferred. These lubricants may be used by mixing two or more kinds in an appropriate ratio.

If necessary, the formulation may contain additional additives other than the above, and the additives listed in the Japanese Pharmacopoeia, the Japanese Pharmaceutical Standards Outside the Pharmacopoeia, the Pharmaceutical Excipients Standards, and the Food Additives Codex. agent can be used.
Such additional additives may be used singly or in admixture in arbitrary amounts as long as they do not cause tablet disintegration time, dissolution properties, hardness, and discomfort in the oral cavity.

As a manufacturing method of this tablet, for example,
1) A method of mixing sulfamethoxazole and trimethoprim, a high-intensity sweetener, a disintegrant, a binder, a lubricant, and optionally further additives, and compressing the mixed powder into tablets (direct compression). tablet method), or 2) a granulated product obtained by mixing sulfamethoxazole and trimethoprim, a disintegrant, and a binder and granulating and sizing, adding a high-intensity sweetener, a lubricant, and A method of producing mixed granules by mixing further additives as desired and compressing them (indirect compression method) is exemplified.
In the case of indirect tableting, the granules are usually used in pharmaceuticals, such as extrusion granulation, stirring granulation, fluid bed granulation, tumbling granulation, and dry granulation. It can be prepared by a granulation method.

When tableting is performed, compression molding is performed at an appropriate normal pressure using a static tableting machine, a rotary tableting machine, or the like. If the tableting pressure is low, the hardness of the tablet will be insufficient and sufficient hardness for handling cannot be ensured, and if the pressure is high, disintegration will be delayed, which is not preferable. In the molding of the present tablet, a mark, a letter, or the like may be added to improve identification.

The hardness (value measured by a hardness meter) of the present tablet may be sufficient for handling (for example, about 10 to 200 N).

The diameter of the tablet is for example 5-7 mm, preferably 5.5-6.5 mm, more preferably about 6 mm.

The thickness of the tablet is, for example, 3.72-4.63 mm, preferably 4.26-4.46 mm, more preferably 4.30-4.40 mm.

The mass of the tablet is, for example, 117.9-151.9 mg, preferably 123.2-130.8 mg, more preferably 125.0-129.0 mg.

The volume of the tablet is, for example, 90-125 mm ³ , preferably 94-119 mm ³ , more preferably 110-113 mm ³ .

The density of the tablet is, for example, 1.07-1.34 mg/mm ³ , preferably 1.07-1.20 mg/mm ³ , more preferably 1.11-1.17 mg/mm ³ .

In the present specification, expressions such as "characteristics required for tablets" and "expected effects" refer to, for example, the tablet friability test method specified in the 17th revision of the Japanese Pharmacopoeia, where the friability is 1.0%. It means the properties and effects of a tablet such that the disintegration time is within 30 minutes in the disintegration test method specified below and/or in the 17th revision of the Japanese Pharmacopoeia.

EXAMPLES The present invention will be described in more detail below with reference to Examples, but the present invention is not limited to these.

Example 1 Production of Tablets Containing 3% by Weight of Sucralose Tablets containing the following ingredients at the compounding ratio (weight basis) shown in the table below were produced by the following procedure.

Manufacture of mixed granules Sulfamethoxazole and trimethoprim as active ingredients, carmellose calcium as disintegrant, and hydroxypropyl cellulose as binder were sieved through a 60-mesh sieve and kneaded with a stirring granulator. An aqueous solution containing 3% ethanol was used for kneading, and the water content during kneading was adjusted to about 30%. After that, granulation was performed using a cylindrical granulator, followed by drying and sizing.
Each condition is as follows.
(Kneading conditions)
・Kneading machine: Stirring granulator
・Stirring blade rotation speed: 100 min ^-1
・Rotation speed of crushing blade: 3000min ^-1
(Granulation conditions)
・ Granulator: Cylindrical granulator ・ Rotation speed: 36 min ^-1

The sieved granules were mixed with sucralose as a sweetener and magnesium stearate as a lubricant to obtain mixed granules.

（硬度）
錠剤硬度計を用いて測定した。
（摩損度）
第１７改正日本薬局方の摩損度試験法に従い測定した。
（崩壊時間）
第１７改正日本薬局方の崩壊試験法（補助盤なし、試験液：精製水）に従い、崩壊試験器を用いて測定した。

結果を下表に示す。

錠剤Ｎｏ．２～９（錠剤の密度：１．０７～１．３４ｍｇ／ｍｍ^３）について、期待する効果（摩損度１％以内、崩壊時間３０分（１８００秒）以内）が得られた。
錠剤Ｎｏ．１（錠剤の密度：１．４１ｍｇ／ｍｍ^３）は崩壊時間が３０分（１８００秒）を超え、錠剤Ｎｏ．１０（錠剤の密度：１．０１ｍｇ／ｍｍ^３）は摩損度が１％を超えており、期待する効果は得られなかった。
Manufacture of tablets The mixed granules (about 128.3 mg) obtained above are compressed using a static tableting machine (pestle: 6.0 mm in diameter) or a rotary tableting machine (pestle: 6.0 mm in diameter). Tablets having different thicknesses were produced by compressing at the compression pressure shown in the table.
The physical properties of each obtained tablet were measured as follows.

(Tablet thickness)
It was measured using a thickness gauge.
(volume/density)
It was calculated by the method shown in the table below.

(hardness)
It was measured using a tablet hardness tester.
(Friability)
It was measured according to the friability test method of the 17th revision of the Japanese Pharmacopoeia.
(collapse time)
It was measured using a disintegration tester according to the disintegration test method of the 17th revision of the Japanese Pharmacopoeia (without auxiliary plate, test solution: purified water).

The results are shown in the table below.

Tablet no. Expected effects (friability within 1%, disintegration time within 30 minutes (1800 seconds)) were obtained for 2 to 9 (tablet density: 1.07 to 1.34 mg/mm ³ ).
Tablet no. Tablet No. 1 (tablet density: 1.41 mg/mm ³ ) had a disintegration time of over 30 minutes (1800 seconds). 10 (tablet density: 1.01 mg/mm ³ ) had a friability exceeding 1%, and the expected effect was not obtained.

表に示されるように、錠剤Ｎｏ．１２～１９について、期待する効果（摩損度１％以内、崩壊時間３０分（１８００秒）以内）が得られた。錠剤Ｎｏ．１１（錠剤の密度：１．０５ｍｇ／ｍｍ^３）は、摩損度が１％を超え、期待する効果は得られなかった。
錠剤Ｎｏ．２０の質量（１５１．９ｍｇ）は、期待する効果が得られる錠剤質量の上限（予測値）を示したものである。厚みを錠剤Ｎｏ．１２と同一（４．４０ｍｍ）とし、密度を効果が得られた上限値（実施例１、錠剤Ｎｏ．２の１．３４ｍｇ／ｍｍ^３）としたときの、錠剤の質量を計算で求めた。
Example 2
The mixed granules (3% by weight of sucralose) obtained in Example 1 were changed in mass, and tablets with a thickness of about 4.4 mm were produced using a rotary tableting machine (pestle: diameter 6.0 mm). did.
Physical properties of each obtained tablet were measured in the same manner as in Example 1.
The results are shown in the table below.

As shown in the table, tablet no. For Nos. 12 to 19, expected effects (friability within 1%, disintegration time within 30 minutes (1800 seconds)) were obtained. Tablet no. 11 (tablet density: 1.05 mg/mm ³ ) had a friability exceeding 1%, and the expected effect was not obtained.
Tablet no. The mass of 20 (151.9 mg) indicates the upper limit (predicted value) of the tablet mass at which the expected effect can be obtained. Tablet no. 12 (4.40 mm), and the density was the upper limit value (1.34 mg/mm ³ of Example 1, tablet No. 2) at which the effect was obtained, the mass of the tablet was obtained by calculation.

Example 3 Production of Pharmaceutical Composition Containing 2% by Weight of Sucralose Tablets containing the following ingredients at the compounding ratio (weight basis) shown in the table below were produced by the following procedure.

Manufacture of mixed granules Sulfamethoxazole and trimethoprim as active ingredients, carmellose calcium as disintegrant, and hydroxypropyl cellulose as binder were sieved through a 60-mesh sieve and kneaded with a stirring granulator. An aqueous solution containing 3% ethanol was used for kneading, and the water content during kneading was adjusted to about 30%. After that, granulation was performed using a cylindrical granulator, followed by drying and sizing.
Each condition is as follows.
(Kneading condition)
・Kneading machine: Stirring granulator
・Stirring blade rotation speed: 100 min ^-1
・Rotation speed of crushing blade: 3000min ^-1
(Granulation conditions)
・ Granulator: Cylindrical granulator ・ Rotation speed: 36 min ^-1

The sieved granules were mixed with sucralose as a sweetener and magnesium stearate as a lubricant to produce mixed granules.

Tablet production The mixed granules (about 127.0 mg) obtained above are tableted using a rotary tableting machine (pestle: diameter 6.0 mm) at the tableting pressure shown in the table below, and the thickness is different. Tablets were manufactured.
The physical properties of each obtained tablet were measured in the same manner as in the above examples.
The results are shown in the table below.

Example 4
The mixed granules (2% by weight of sucralose) obtained in Example 3 were changed in mass, and tablets having a thickness of about 4.4 mm were produced using a rotary tableting machine (pestle: diameter 6.0 mm). did.
For each obtained tablet, the physical properties of the tablet were measured in the same manner as in the above examples.
The results are shown in the table below.

Example 5
Tablets were produced from the mixed granules (sucralose 2% by weight) obtained in Example 3 using a rotary tableting machine (punch: diameter 6.0 mm) while varying the mass and tablet thickness.
The physical properties of each obtained tablet were measured in the same manner as in the above examples.
The results are shown in the table below.

Example 6: Manufacture of tablets containing 1% by weight of sucralose Tablets containing the following ingredients at the compounding ratio (weight basis) shown in the table below were manufactured using a method similar to the procedure described in the above example, A tablet having the physical properties shown in Table 10 was obtained.

高甘味度甘味剤を添加することにより嗜好率が有意に向上した。
Example 7: Evaluation of palatability using rats The effect of adding a high-intensity sweetener was evaluated by a two-bottle choice palatability experiment.
58.0 mg of sulfamethoxazole and 11.6 mg of trimethoprim were dissolved in 900 mL of tap water, and the volume was adjusted to 1 L with tap water to prepare an aqueous drug substance solution.
Two water bottles for measurement were prepared, and the prepared drug substance aqueous solution was directly put into one of the bottles. As a test solution, sucralose (1% or 2%) dissolved in the drug substance aqueous solution was placed in the other bottle.
SD rats (7 weeks old: obtained from Charles River) were presented with two bottles at the same time and allowed to take them ad libitum. By weighing the water bottle for measurement after ad libitum intake, each intake was recorded, and the preference rate was calculated by the following formula.

Preference rate (%) = intake of test aqueous solution (g) / total intake of two bottles presented (g) × 100

The results are shown in the table below.

Addition of the high-intensity sweetener significantly improved the preference rate.

Example 8: Investigation on tablet compliance Tablets of the present invention (diameter: about 6.0 mm, thickness: about 4.0 mm) were prepared using the method described in Example 3 above (manufacturing conditions were the same as those for tablet No. 24). 4 mm, mass: about 0.13 g).
The tablet of the present invention was administered to patients (total of 18 people) who were taking a commercially available ST combination drug (ordinary tablet (diameter: about 11.0 mm, thickness: about 5.1 mm, mass: about 0.50 g) or granules). was taken, and a questionnaire survey was conducted on its usability.
(Method)
Switching the medication to the patient from the ST combination drug currently being taken to the tablet of the present invention, the acceptability at the time of administration (three-step visual rating scale: positive /neutral/negative), preparation time, dosing time, dosing method, and impression of dosing.
(result)
Acceptability (positive/neutral/negative), before switching to the tablet of the present invention, for ordinary tablets: positive: 1 case / neutral: 2 cases / negative: 6 cases, for granules: positive: 2 cases / neutral: 1 case / negative: 6 cases. After switching to the tablet of the present invention, positive: 7 cases/neutral: 1 case/negative: 1 case, positive: 6 cases/neutral: 3 cases/negative: 0 cases, respectively.
Before switching to the tablets of the present invention, the preparation time/dose time (median) was 60/70 seconds for regular tablets and 90/145 seconds for granules. After switching to the tablets of the invention, they were 30/10 seconds and 20/40 seconds, respectively.
The number of cases requiring the use of syrup, ice cream, etc. for dosing assistance was 5 for ordinary tablets, 4 for granules, and 3 for tablets of the present invention, and was the lowest for the tablets of the present invention.
As described above, the tablet of the present invention greatly improved acceptability at the time of administration, especially in young patients, and significantly shortened both the preparation time for administration and the administration time.

Example 9: Bioequivalence test Tablets of the present invention (manufacturing conditions are the same as tablet No. 24, diameter: about 6.0 mm, thickness: about 4.4 mm, mass: about 0.13 g) and commercially available Regarding ST combination tablets (ordinary tablets (diameter: about 11.0 mm, thickness: about 5.1 mm, weight: about 0.50 g), the March 19, 2010, PSEHB Notification No. 0319 No. 1) "Guidelines for Bioequivalence Studies of Generic Drugs" and "Guidelines for Bioequivalence Studies of Oral Solid Formulations with Different Contents" As a result, the dissolution behavior of the tablet of the present invention and the ordinary tablet were shown to be equivalent.
Under all the dissolution test conditions, the judgment criteria specified in Chapter 5 "Judgment of equivalence of dissolution behavior" of the guidelines were satisfied.

It becomes possible to provide small tablets containing sulfamethoxazole and trimethoprim, which are used as medicines for the treatment and prevention of pneumonia and infectious diseases.

Claims (21)

A tablet containing 90.0-110.0 mg of sulfamethoxazole, 18.0-22.0 mg of trimethoprim and 1-3% by weight of a high-intensity sweetener and having a tablet volume of 94-119 mm ³ . 2. The tablet of claim 1, wherein the high intensity sweetener is one or more selected from the group consisting of sucralose, stevia, aspartame, acesulfame potassium, glycyrrhizic acid (dipotassium glycyrrhizinate), thaumatin, advantame and saccharin. 3. The tablet of Claim 2, wherein the intense sweetener is sucralose. The tablet according to any of claims 1-3, wherein the amount of sulfamethoxazole is about 100 mg and the amount of trimethoprim is about 20 mg. A tablet according to any preceding claim, wherein the amount of intense sweetener is about 2% by weight. 4. The tablet according to any one of claims 1 to 3, further comprising at least one of hydroxypropylcellulose and carmellose calcium. Contains 77.9 to 79.5% by weight of sulfamethoxazole and 15.5 to 15.9% by weight of trimethoprim with respect to the tablet mass, the tablet thickness is 3.72 to 4.63 mm, and the tablet mass is 117.9-151.9 mg and a tablet density of 1.07-1.34 mg/mm ³ . 8. The tablet according to claim 7, further comprising 1 to 3% by weight of a high-intensity sweetener. The tablet according to claim 7 or 8, wherein the tablet thickness is 4.26-4.46 mm. The tablet according to claim 7 or 8, wherein the tablet weight is 123.2-130.8 mg. A tablet according to claim 7 or 8, having a tablet density of 1.07-1.20 mg/mm ³ . Tablets according to claim 7 or 8, having a tablet volume of 94-119 mm ³ . 9. The tablet of Claim 8, wherein the intense sweetener is sucralose. The tablet according to claim 7 or 8, wherein the amount of sulfamethoxazole is 90.0-110.0 mg and the amount of trimethoprim is 18.0-22.0 mg. 15. The tablet of Claim 14, wherein the amount of sulfamethoxazole is about 100 mg and the amount of trimethoprim is about 20 mg. 9. The tablet according to claim 7 or 8, which has a friability of 1.0% or less in the tablet friability test method specified in the Japanese Pharmacopoeia 17th Edition. 9. The tablet according to claim 7 or 8, which has a disintegration time of 30 minutes or less in the disintegration test method specified in the 17th revision of the Japanese Pharmacopoeia. 17. The tablet according to claim 16, wherein the amount of sucralose is 1-2% by weight. 17. The tablet of Claim 16, wherein the amount of sucralose is about 2% by weight. 18. The tablet according to claim 17, wherein the amount of sucralose is 1-2% by weight. 18. The tablet of Claim 17, wherein the amount of sucralose is about 2% by weight.