Laxative tablets

Abstract

To provide a laxative tablet that, when suspended in water, yields particles having fine sizes and disintegrates in a short time.SOLUTION: Provided is a laxative tablet that includes magnesium oxide as a main constituent. (1) The particles to be formed by the tablet suspended in water has a volume-based 50% particle diameter (D50) of 70 μm or less, as determined by laser diffractometry. (2) The particles to be formed by the tablet suspended in water has a volume-based 90% particle diameter (D90) of 130 μm or less, as determined by laser diffractometry. (3) The tablet has a dissolution time of 10 seconds or less when suspended in water, in accordance with Dissolution Tests in the Japanese Pharmacopoeia General Tests.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a laxative tablet containing magnesium oxide as a main component, and more particularly to a laxative tablet which has a fine particle size when suspended in water and disintegrates in a short time, and a method for producing the same. [Background technology]

[0002] Tablets containing magnesium oxide as a main component have been known as antacid or laxative tablets and are currently in wide use. These tablets containing magnesium oxide are produced by compounding magnesium oxide with additives such as a binder and a disintegrant, and compressing the mixture.

[0003] The present applicant has proposed an antacid / laxative tablet that has a high magnesium oxide content, a short disintegration time, and is substantially free of tableting problems, blackening, and tableting spots (Patent Document 1). The tablet described in Patent Document 1 is characterized by containing 88 to 97% by weight of magnesium oxide having a specific particle size, 1 to 10% by weight of crystalline cellulose or starch as a binder, and 1 to 3.5% by weight of croscaromellose sodium or carboxystarch sodium as a disintegrant.

[0004] The applicant also proposed an antacid / laxative tablet that has a high magnesium oxide content, a short disintegration time, and maintains this short disintegration time for a long period of time, and is less susceptible to wear and chipping (Patent Document 2). The tablet described in Patent Document 2 is characterized by containing two types of compounds as disintegrants in a specific ratio and having a specific shape.

[0005] When administering medicine to patients with swallowing disorders, tube feeding is sometimes chosen. If the medicine used for tube feeding is in the form of a tablet, it must be crushed. However, this crushed preparation has been pointed out to have an effect on the physicochemical stability and efficacy of the preparation after crushing, and there are many other issues, such as the complication of dispensing work. Therefore, a method was proposed in which tablets are disintegrated and suspended in water without being crushed, and the dispersion is administered through a tube feeding.

[0006] The present applicant has proposed an aqueous dispersion containing magnesium oxide suitable for administration through a feeding tube, and a tablet therefor (Patent Document 3). The tablet described in Patent Document 3 is characterized by containing magnesium oxide having a specific particle size, a specific binder, and a disintegrant in a certain ratio. It is said that the tablet disintegrates quickly in water, and the obtained aqueous dispersion can be smoothly administered without causing blockage in the feeding tube. In addition, it is described that the diameter of a feeding tube is generally 1.0 to 6.0 mm, but that for adults, tubes of about 2.7 to 4.0 mm are often used.

[0007] For tube administration, an 8Fr (outer diameter 2.7 mm) tube is usually used for adults, but for children, a thinner 3Fr (outer diameter 1.0 mm) or 4Fr (outer diameter 1.3 mm) tube is used depending on the body weight (Non-Patent Documents 1 and 2). Therefore, there has been a demand for an aqueous dispersion containing magnesium oxide and tablets therefor that can be administered smoothly without causing blockage of particles in a 3Fr tube. However, it has been difficult to pass an aqueous suspension of magnesium oxide tablets manufactured by a conventional formulation smoothly through a 3Fr tube.

[0008] Furthermore, when magnesium oxide tablets are administered orally, there is a demand for the tablets to disintegrate quickly in the oral cavity in order to reduce the burden on patients of taking medication. [Prior art documents] [Patent documents]

[0009] [Patent Document 1] JP 2003-146889 A [Patent Document 2] WO2011-030659 [Patent Document 3] Patent Publication No. 2006-022060 [Non-patent literature]

[0010] [Non-Patent Document 1] Kobe University School of Medicine, Pediatrics, "New Edition: Management of Premature Newborns," Japan Pediatric Medical Publishing, September 2000, p. 133 [Non-Patent Document 2] Katsuya Suemaru and 6 others, "Drug permeability through nasogastric tubes for children," Medical Pharmacy, Japan Medical and Pharmaceutical Society, June 2003, Vol. 29, No. 3, pp. 337-340 Summary of the Invention [Problem to be solved by the invention]

[0011] The first object of the present invention is to provide a laxative tablet which generates particles with a small diameter when suspended in water and disintegrates in a short time, and the second object of the present invention is to provide a laxative tablet which generates particles when suspended in water and can smoothly pass through a 3Fr tube for tube feeding and can be used for tube feeding in children. [Means for solving the problem]

[0012] As a result of extensive research, the inventors have discovered that by using a specific type of disintegrant, blending ratio and manufacturing method, it is possible to prepare a laxative tablet that disintegrates in a short time and produces fine particles when the tablet is suspended in water, and thus completed the present invention.

[0013] That is, the present invention provides the following embodiments: (1) A laxative tablet containing magnesium oxide as its main ingredient, (i) the particles generated when the tablet is suspended in water have a volume-based 50% particle size (D50) of 70 μm or less as measured by a laser diffraction method; (ii) The particles generated when the tablet is suspended in water have a volume-based 90% particle size (D90) of 130 μm or less as measured by a laser diffraction method; and (iii) The tablet has a disintegration time of 10 seconds or less when suspended in water according to the disintegration test method of the general test method of the Japanese Pharmacopoeia.

[0014] Furthermore, the laxative tablet of the present invention preferably has the following form. (2) A laxative tablet comprising a disintegrant 1 and a disintegrant 2, the disintegrant 1 comprising 0.5 to 3.5% by weight of croscarmellose sodium, and the disintegrant 2 comprising 0.5 to 3.5% by weight of insoluble polyvinylpyrrolidone, the weight ratio of which is 0.1 to 5:1. (3) A laxative tablet in which the disintegrant 2 is insoluble polyvinylpyrrolidone and the volume-based 50% particle size (D50) measured by a laser diffraction method is 15 μm or less. (4) A laxative tablet containing 80 to 96% by weight of magnesium oxide. (5) Laxative tablets containing 50 to 250 mg of magnesium oxide per tablet. (6) Laxative tablets for children. (7) Laxative tablets for tube feeding in children. (8) (A1) a step of mixing magnesium oxide having a volume-based 50% particle size (D50) of 0.5 to 10 μm as measured by a laser diffraction method, crystalline cellulose as a binder, croscaromellose sodium as a disintegrant 1, and insoluble polyvinylpyrrolidone as a disintegrant 2, and then dry granulating the mixture to prepare magnesium oxide granules; (A2) blending the resulting magnesium oxide granules with crystalline cellulose as a binder, a lubricant, and optionally a sweetener; and (A3) A process for compressing the obtained granules into tablets. A laxative tablet whose main ingredient is magnesium oxide. (9) (B1) A step of mixing magnesium oxide having a volume-based 50% particle size (D50) of 0.5 to 10 μm measured by a laser diffraction method, crystalline cellulose as a binder, and insoluble polyvinylpyrrolidone as a disintegrant 2, and then dry granulating the mixture to prepare magnesium oxide granules; (B2) blending the magnesium oxide granules obtained with croscarmellose sodium as a disintegrant 1, crystalline cellulose as a binder, a lubricant, and optionally a sweetener; and (B3) compressing the obtained granules into tablets. A laxative tablet whose main ingredient is magnesium oxide.

[0015] Furthermore, according to the present invention, the laxative tablet of the present invention can be prepared by the following production methods (A) and (B). Manufacturing method (A) (A1) a step of mixing magnesium oxide having a volume-based 50% particle size (D50) of 0.5 to 10 μm as measured by a laser diffraction method, crystalline cellulose as a binder, croscaromellose sodium as a disintegrant 1, and insoluble polyvinylpyrrolidone as a disintegrant 2, and then dry granulating the mixture to prepare magnesium oxide granules; (A2) blending the resulting magnesium oxide granules with crystalline cellulose as a binder, a lubricant, and optionally a sweetener; and (A3) A step of compressing the obtained granules into tablets A method for producing a laxative tablet containing magnesium oxide as a main ingredient.

[0016] Manufacturing method (B) (B1) a step of mixing magnesium oxide having a volume-based 50% particle size (D50) of 0.5 to 10 μm as measured by a laser diffraction method, crystalline cellulose as a binder, and insoluble polyvinylpyrrolidone as a disintegrant 2, and then dry granulating the mixture to prepare magnesium oxide granules; (B2) blending the magnesium oxide granules obtained with croscarmellose sodium as a disintegrant 1, crystalline cellulose as a binder, a lubricant, and optionally a sweetener; and (B3) A step of compressing the obtained granules into tablets A method for producing a laxative tablet containing magnesium oxide as a main ingredient. Effect of the Invention

[0017] According to the present invention, a laxative tablet is provided which generates fine particles when suspended in water and disintegrates in a short time. When administering the tablet through a tube to a patient, particularly a child, the tablet can be disintegrated and suspended in water, allowing for smooth administration without clogging a thinner tube than before. Furthermore, the tablet disintegrates quickly in the oral cavity, reducing the burden on the patient when taking the tablet. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0018] The present invention will be specifically described below.

[0019] <Laxative tablets> (Magnesium oxide) The magnesium oxide contained in the laxative tablet of the present invention has a volume-based 50% particle size (D50) of 0.5 to 10 μm, preferably 1 to 7 μm, measured by a laser diffraction method. The content of magnesium oxide in the tablet is 80 to 96% by weight, preferably 82 to 94% by weight (hence, magnesium oxide is the main component). The amount of magnesium oxide contained per tablet is 50 to 250 mg, preferably 70 to 230 mg, more preferably 90 to 210 mg. As such magnesium oxide, for example, Magnesium Oxide T (manufactured by Kyowa Chemical Industry Co., Ltd.) can be used.

[0020] (Disintegrant) The laxative tablet of the present invention contains croscarmellose sodium as disintegrant 1 and insoluble polyvinylpyrrolidone as disintegrant 2. The content of croscarmellose sodium in the tablet is 0.5-3.5% by weight, preferably 1-3% by weight. The content of insoluble polyvinylpyrrolidone in the tablet is 0.5-3.5% by weight, preferably 1-3% by weight. The weight ratio of disintegrant 1 to disintegrant 2 in the tablet is 0.1-5:1, preferably 0.3-4:1. The insoluble polyvinylpyrrolidone has a volume-based 50% particle size (D50) of 15 μm or less, preferably 10 μm or less, measured by a laser diffraction method. As the insoluble polyvinylpyrrolidone having a volume-based 50% particle size (D50) of 15 μm or less, for example, Kollidon CL-M (manufactured by BASF) can be used.

[0021] (Binding Agent) The laxative tablet of the present invention contains a binder. Examples of binders include crystalline cellulose, sodium carboxymethylcellulose, and low-substituted hydroxypropylcellulose. Preferably, crystalline cellulose is used. The content of the binder in the tablet is 3 to 15% by weight, preferably 5 to 13% by weight.

[0022] (lubricant) The laxative tablet of the present invention contains a lubricant. Examples of lubricants include stearic acid and its salts (Na, Mg, Ca salts). Preferably, calcium stearate is used. The content of the lubricant in the tablet is 0.5 to 2% by weight, preferably 0.7 to 1.5% by weight.

[0023] (Sweetener) The laxative tablet of the present invention contains a sweetener. Examples of sweeteners include aspartame, acesulfame potassium, and sucralose. Preferably, one or more selected from the group consisting of aspartame and acesulfame potassium are used. The content of the sweetener in the tablet is 0.1 to 1% by weight, preferably 0.2 to 0.5% by weight.

[0024] (Tablet size and weight) The diameter of the laxative tablet of the present invention is 5 to 12 mm, preferably 5 to 10 mm, and more preferably 5 to 8 mm. The thickness is 2 to 6 mm, preferably 2 to 5 mm, and more preferably 2.5 to 4.5 mm. The weight per tablet is 50 to 300 mg, preferably 70 to 280 mg, and more preferably 90 to 250 mg. By setting the size and weight of the tablet within the above ranges, the tablet can be made easy to swallow for children.

[0025] (Tablet disintegration) The laxative tablet of the present invention has a disintegration time of 10 seconds or less, preferably 9 seconds or less, and more preferably 8 seconds or less, when suspended in water, as measured by the disintegration test method of the general test method of the Japanese Pharmacopoeia. The shorter disintegration time reduces the burden on patients when taking the tablet.

[0026] (Particle size of tablet after suspension in water) When the laxative tablet of the present invention is suspended in water and the resulting suspended particles are measured by a laser diffraction method, the volume-based 50% particle size (D50) is 70 μm or less, preferably 65 μm or less, and the volume-based 90% particle size (D90) measured by the same method is 130 μm or less, preferably 120 μm or less.

[0027] (50% particle size by volume) The volume-based 50% particle size is the particle size at 50 vol% in a cumulative distribution showing the volume ratio of particles equal to or smaller than a certain particle size.

[0028] (Administration method and dosage) The tablet of the present invention is administered orally or by tube feeding after disintegration and suspension in water for laxative purposes. The dosage depends on the purpose or condition. A typical dosage is 2 g per day for an adult, and for children, the dosage is based on their age and weight.

[0029] <Manufacturing method of laxative tablets> The laxative tablet of the present invention can be manufactured by the following manufacturing method (A) or (B). That is, by adopting these manufacturing methods, tablets having a predetermined particle size (D50 and D90) and a predetermined disintegration time can be obtained.

[0030] Manufacturing method (A) (A1) a step of mixing magnesium oxide having a volume-based 50% particle size (D50) of 0.5 to 10 μm as measured by a laser diffraction method, crystalline cellulose as a binder, croscaromellose sodium as a disintegrant 1, and insoluble polyvinylpyrrolidone as a disintegrant 2, and then dry granulating the mixture to prepare magnesium oxide granules; (A2) blending the resulting magnesium oxide granules with crystalline cellulose as a binder and a lubricant; and (A3) A step of compressing the obtained granules into tablets A method for producing a laxative tablet containing magnesium oxide as a main ingredient.

[0031] Manufacturing method (B) (B1) a step of mixing magnesium oxide having a volume-based 50% particle size (D50) of 0.5 to 10 μm as measured by a laser diffraction method, crystalline cellulose as a binder, and insoluble polyvinylpyrrolidone as a disintegrant 2, and then dry granulating the mixture to prepare magnesium oxide granules; (B2) blending the magnesium oxide granules obtained with croscarmellose sodium as a disintegrant 1, microcrystalline cellulose as a binder, and a lubricant; and (B3) A step of compressing the obtained granules into tablets A method for producing a laxative tablet containing magnesium oxide as a main ingredient.

[0032] The above manufacturing method is characterized in that a granule is first prepared, the obtained granule is compressed into tablets, and disintegrant 1 and disintegrant 2 are used as essential ingredients. In manufacturing method (A), disintegrant 1 and disintegrant 2 are blended when the granule is prepared. In manufacturing method (B), disintegrant 2 is blended when the granule is prepared, and disintegrant 1 is blended after the granule is made. Crystalline cellulose is blended twice, once when the granule is prepared and once after the granule is made. The same crystalline cellulose may be blended at each timing, or different crystalline cellulose may be blended.

[0033] The laxative tablet of the present invention can be produced by either of the above-mentioned production methods (A) and (B). However, it is more preferable to use the production method (A) since the disintegration time of the obtained tablet is shorter.

[0034] Furthermore, by using the production method (A), the tablet of the present invention having the following configuration can be prepared. A tablet formulation of tablet granules containing the following (1A) and (2A): (1A) Dry granulation granules comprising magnesium oxide having a volume-based 50% particle size (D50) of 0.5 to 10 μm measured by a laser diffraction method, crystalline cellulose as a binder, croscaromellose sodium as a disintegrant 1, and insoluble polyvinylpyrrolidone as a disintegrant 2; (2A) Microcrystalline cellulose as a binder and a lubricant present in a mixed state with the dry granules.

[0035] Furthermore, by using the production method (B), the tablet of the present invention having the following configuration can be prepared. A tablet formulation of tablet granules containing the following (1B) and (2B): (1B) Dry granulation granules comprising magnesium oxide having a volume-based 50% particle size (D50) of 0.5 to 10 μm measured by a laser diffraction method, crystalline cellulose as a binder, and insoluble polyvinylpyrrolidone as a disintegrant 2; (2B) Croscarmellose sodium as a disintegrant 1, microcrystalline cellulose as a binder, and a lubricant, present in a mixed state with the dry granules.

[0036] Here, the tablet granules refer to granules before tableting for use in tableting.

[0037] The tablets obtained by manufacturing method (A) have the granules prepared in (1A) as a core (called internal additive) around which the binder in (2A) is present (called external additive). Similarly, the tablets obtained by manufacturing method (B) have the granules prepared in (1B) as a core (called internal additive) around which the disintegrant and binder in (2B) are present (called external additive). EXAMPLES

[0038] The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples. In the examples and comparative examples, the various physical properties were measured by the following methods.

[0039] (a) Collapse time The disintegration time of laxative tablets was measured according to the General Test Method / Disintegration Test Method of the 17th Revised Japanese Pharmacopoeia. Water was used as the test liquid.

[0040] (b) Volume-based 50% particle size (D50) (magnesium oxide) 0.7 g of magnesium oxide and 70 mL of 0.2% sodium hexametaphosphate aqueous solution were added to a beaker, and dispersed (3 minutes) using an ultrasonic homogenizer (Nippon Seiki Co., Ltd., US-300). The volume-based 50% particle size (D50) of magnesium oxide was measured using a laser diffraction scattering type particle size distribution measuring device (Nikkiso Co., Ltd., Microtrack).

[0041] (c) Volume-based 50% particle size (D50) and volume-based 90% particle size (D90) after suspension in water (laxative tablets) Ten tablets and 40 mL of ion-exchanged water were added to a beaker, and after leaving it to stand for 10 seconds, the resulting precipitate was stirred with a glass rod to form a suspension. The volume-based 50% particle size (D50) and volume-based 90% particle size (D90) of the laxative tablet after suspension in water were measured using a laser diffraction scattering type particle size distribution analyzer (Seishin Enterprise, LMS-2000e).

[0042] (d) Tube passability test The plunger of a catheter syringe (Nipro, Enteral Nutrition Infusion Set Syringe DS 20mL Catheter Yellow) was removed, 6 tablets were placed in the outer cylinder, the plunger was returned, 20mL of hot water at 55°C was sucked up, the tip of the cylinder was capped and left to stand for 5 minutes. After 5 minutes, the syringe was turned 90 degrees 15 times by hand to obtain a suspension. The catheter syringe was connected to a 3Fr, 40cm long enteral nutrition tube (Atom Medical, Atom Nutrition Catheter T), and the suspension and 20mL of ion-exchanged water for washing were injected to confirm tube passability. The test was performed three times, and each was evaluated as ○ if the tube was not blocked and × if it was blocked.

[0043] Example 1 Laxative tablets were manufactured by the following manufacturing method according to the recipe in Table 1. In Tables 1 to 6, "internal additives" means the agents used in the preparation of the granules, and "external additives" means the agents further added to the granules once obtained. In Tables 1 to 6, the mg indication indicates the relative amount of each component when magnesium oxide is taken as 100.0 mg.

[0044] Magnesium oxide with a volume-based 50% particle size (D50) of 6.5 μm: 1500 g, crystalline cellulose: 168 g, croscarmellose sodium: 58.5 g, and insoluble polyvinylpyrrolidone with a volume-based 50% particle size (D50) of 5.4 μm by laser diffraction method 1: 12 g were mixed and granulated with a roll pressure of 5 MPa using a roll molding type dry granulator. The granulated material was pulverized with an oscillator type pulverizer to prepare granules. Calcium stearate: 16 g, crystalline cellulose: 34.6 g, aspartame: 1.3 g, and acesulfame potassium: 2.7 g were added to the obtained granules (1540.7 g), and mixed in a container type mixer to prepare tablet granules. The obtained tablet granules were tableted at a tableting pressure of 4.5 kN using a rotary tablet press equipped with two 8R punches, each 6 mm in diameter, to obtain magnesium oxide tablets weighing 120 mg, 6 mm in diameter, and 3.4 mm in thickness. Table 7 shows the results of the 50% volume particle size (D50), 90% volume particle size (D90), disintegration time, and tube passability test for the obtained magnesium oxide tablets after suspension in water.

[0045] Example 2 Laxative tablets were produced according to the formulation in Table 1. The same procedure as in Example 1 was repeated except that the amount of croscarmellose sodium added was changed to 52.5 g and the amount of insoluble polyvinylpyrrolidone 1 added was changed to 18 g, to obtain magnesium oxide tablets weighing 120 mg per tablet, with a diameter of 6 mm and a thickness of 3.4 mm. Table 7 shows the results of the 50% volume particle size (D50), 90% volume particle size (D90), disintegration time, and tube passability test of the obtained magnesium oxide tablets after suspension in water.

[0046] Example 3 Laxative tablets were produced according to the formulation in Table 1. The same procedure as in Example 1 was repeated except that the amount of croscarmellose sodium added was changed to 43.5 g and the amount of insoluble polyvinylpyrrolidone 1 added was changed to 27 g, to obtain magnesium oxide tablets weighing 120 mg per tablet, with a diameter of 6 mm and a thickness of 3.4 mm. Table 7 shows the results of the 50% volume particle size (D50), 90% volume particle size (D90), disintegration time, and tube passability test of the obtained magnesium oxide tablets after suspension in water.

[0047] Example 4 Laxative tablets were produced according to the formulation in Table 2. The same procedure as in Example 1 was repeated except that the amount of croscarmellose sodium added was changed to 35.25 g and the amount of insoluble polyvinylpyrrolidone 1 added was changed to 35.25 g, to obtain magnesium oxide tablets weighing 120 mg per tablet, with a diameter of 6 mm and a thickness of 3.4 mm. Table 8 shows the results of the 50% volume particle size (D50), 90% volume particle size (D90), disintegration time, and tube passability test of the obtained magnesium oxide tablets after suspension in water.

[0048] Example 5 Laxative tablets were produced according to the formulation in Table 2. The same procedure as in Example 1 was repeated except that the amount of croscarmellose sodium added was changed to 27 g and the amount of insoluble polyvinylpyrrolidone 1 added was changed to 43.5 g, to obtain magnesium oxide tablets weighing 120 mg per tablet, with a diameter of 6 mm and a thickness of 3.4 mm. Table 8 shows the results of the 50% volume particle size (D50), 90% volume particle size (D90), disintegration time, and tube passability test of the obtained magnesium oxide tablets after suspension in water.

[0049] Example 6 Laxative tablets were produced according to the formulation in Table 2. The same procedure as in Example 1 was repeated except that the amount of croscarmellose sodium added was changed to 18 g and the amount of insoluble polyvinylpyrrolidone 1 added was changed to 52.5 g, to obtain magnesium oxide tablets weighing 120 mg per tablet, with a diameter of 6 mm and a thickness of 3.4 mm. Table 8 shows the results of the 50% volume particle size (D50), 90% volume particle size (D90), disintegration time and tube passability test of the obtained magnesium oxide tablets after suspension in water.

[0050] Example 7 Laxative tablets were produced according to the formulation in Table 3. The same procedure as in Example 1 was repeated except that the amount of croscarmellose sodium added was changed to 12 g and the amount of insoluble polyvinylpyrrolidone 1 added was changed to 58.5 g, to obtain magnesium oxide tablets weighing 120 mg per tablet, with a diameter of 6 mm and a thickness of 3.4 mm. Table 9 shows the results of the 50% volume particle size (D50), 90% volume particle size (D90), disintegration time, and tube passability test of the obtained magnesium oxide tablets after suspension in water.

[0051] Example 8 According to the formulation in Table 3, laxative tablets were manufactured. 1500g of magnesium oxide with a volume-based 50% particle size (D50) of 6.5 μm, 168g of crystalline cellulose, and 1:27g of insoluble polyvinylpyrrolidone with a volume-based 50% particle size (D50) of 5.4 μm by laser diffraction were mixed and granulated with a roll pressure of 5 MPa using a roll molding type dry granulator. The granulated material was pulverized with an oscillator type pulverizer to produce granules. To the obtained granules (1539.4 g), 39.5g of croscarmellose sodium, 16.3g of calcium stearate, 35.4g of crystalline cellulose, 1.4g of aspartame, and 2.7g of acesulfame potassium were added, and mixed in a container type mixer to produce tablet granules. The obtained tablet granules were tableted under the same conditions as in Example 1 to obtain magnesium oxide tablets each weighing 120 mg, with a diameter of 6 mm and a thickness of 3.4 mm. The results of the 50% volume-based particle size (D50), 90% volume-based particle size (D90), disintegration time and tube passability test of the obtained magnesium oxide tablets after suspension in water are shown in Table 9.

[0052] Example 9 Magnesium oxide with a volume-based 50% particle size (D50) of 6.5 μm: 3000 g, crystalline cellulose: 336 g, croscarmellose sodium: 87 g, and insoluble polyvinylpyrrolidone with a volume-based 50% particle size (D50) of 5.4 μm by laser diffraction method: 1:54 g were mixed and granulated with a roll pressure of 5 MPa using a roll molding type dry granulator. The granulated material was pulverized with an oscillator type pulverizer to prepare granules. Calcium stearate: 31.9 g, crystalline cellulose: 69.1 g, aspartame: 2.7 g, and acesulfame potassium: 5.3 g were added to the obtained granules (3081.4 g), and the mixture was mixed in a container type mixer to prepare tablet granules. The obtained tablet granules were tableted at a tableting pressure of 7 kN using a rotary tablet press equipped with two 11R punches, each with a diameter of 7.5 mm, to obtain magnesium oxide tablets weighing 240 mg, with a diameter of 7.5 mm and a thickness of 4.2 mm. The results of the 50% volume particle size (D50), 90% volume particle size (D90), disintegration time and tube passability test of the obtained magnesium oxide tablets after suspension in water are shown in Table 9.

[0053] Comparative Example 1 Laxative tablets were produced according to the formulation in Table 4. The same production procedure as in Example 1 was repeated except that the amount of croscarmellose sodium added was changed to 70.5 g and insoluble polyvinylpyrrolidone 1 was not added, to obtain magnesium oxide tablets weighing 120 mg per tablet, with a diameter of 6 mm and a thickness of 3.4 mm. The results of the 50% volume-based particle size (D50), 90% volume-based particle size (D90), disintegration time, and tube passability test of the obtained magnesium oxide tablets after suspension in water are shown in Table 10.

[0054] Comparative Example 2 Laxative tablets were produced according to the formulation in Table 4. The same procedure as in Example 1 was repeated except that the amount of croscarmellose sodium added was changed to 64.5 g and the amount of insoluble polyvinylpyrrolidone 1 added was changed to 6 g, to obtain magnesium oxide tablets weighing 120 mg per tablet, with a diameter of 6 mm and a thickness of 3.4 mm. The results of the 50% volume particle size (D50), 90% volume particle size (D90), disintegration time, and tube passability test of the obtained magnesium oxide tablets after suspension in water are shown in Table 10.

[0055] Comparative Example 3 Laxative tablets were produced according to the formulation in Table 4. The same procedure as in Example 1 was repeated except that the amount of croscarmellose sodium added was changed to 6 g and the amount of insoluble polyvinylpyrrolidone 1 added was changed to 64.5 g, to obtain magnesium oxide tablets weighing 120 mg per tablet, with a diameter of 6 mm and a thickness of 3.4 mm. The results of the 50% volume particle size (D50), 90% volume particle size (D90), disintegration time, and tube passability test of the obtained magnesium oxide tablets after suspension in water are shown in Table 10.

[0056] Comparative Example 4 Laxative tablets were produced according to the formulation in Table 4. The same procedure as in Example 1 was repeated except that croscarmellose sodium was not added and the amount of insoluble polyvinylpyrrolidone 1 added was changed to 70.5 g, to obtain magnesium oxide tablets weighing 120 mg per tablet, with a diameter of 6 mm and a thickness of 3.4 mm. The results of the 50% volume-based particle size (D50), 90% volume-based particle size (D90), disintegration time and tube passability test of the obtained magnesium oxide tablets after suspension in water are shown in Table 10.

[0057] Comparative Example 5 Laxative tablets were produced according to the formulation in Table 5. The same procedure was followed as in Example 1, except that insoluble polyvinylpyrrolidone 2 having a volume-based 50% particle size (D50) of 118 μm as determined by laser diffraction was used instead of insoluble polyvinylpyrrolidone 1, to obtain magnesium oxide tablets weighing 120 mg per tablet, with a diameter of 6 mm and a thickness of 3.4 mm. Table 11 shows the volume-based 50% particle size (D50), volume-based 90% particle size (D90), disintegration time, and tube passability test results for the obtained magnesium oxide tablets after suspension in water.

[0058] Comparative Example 6 Laxative tablets were produced according to the formulation in Table 5. The same production procedure as in Example 1 was repeated except that insoluble polyvinylpyrrolidone 3 having a volume-based 50% particle size (D50) of 29 μm as determined by laser diffraction was used instead of insoluble polyvinylpyrrolidone 1, to obtain magnesium oxide tablets weighing 120 mg per tablet, with a diameter of 6 mm and a thickness of 3.4 mm. The volume-based 50% particle size (D50), volume-based 90% particle size (D90), disintegration time, and tube passability test results for the magnesium oxide tablets obtained after suspension in water are shown in Table 11.

[0059] Comparative Example 7 Laxative tablets were produced according to the formulation in Table 5. The same procedure was followed as in Example 1, except that insoluble polyvinylpyrrolidone 4 having a volume-based 50% particle size (D50) of 17 μm as determined by laser diffraction was used instead of insoluble polyvinylpyrrolidone 1, to obtain magnesium oxide tablets weighing 120 mg per tablet, with a diameter of 6 mm and a thickness of 3.4 mm. The volume-based 50% particle size (D50), volume-based 90% particle size (D90), disintegration time, and tube passability test results for the obtained magnesium oxide tablets after suspension in water are shown in Table 11.

[0060] Comparative Example 8 According to the formulation in Table 6, laxative tablets were manufactured. After mixing 1500g of magnesium oxide with a volume-based 50% particle size (D50) of 6.5 μm and 168g of crystalline cellulose, the mixture was granulated in a roll molding type dry granulator at a roll pressure of 5 MPa. The granulated product was pulverized in an oscillator type pulverizer to produce granules. To the obtained granules (1438.5g), 37.5g of croscarmellose sodium, 23.3g of insoluble polyvinylpyrrolidone 1 with a volume-based 50% particle size (D50) of 5.4 μm by laser diffraction method, 15.5g of calcium stearate, 33.6g of crystalline cellulose, 1.3g of aspartame, and 2.6g of acesulfame potassium were added, and the mixture was mixed in a container type mixer to produce tablet granules. The obtained tablet granules were tableted under the same conditions as in Example 1 to obtain magnesium oxide tablets each weighing 120 mg, with a diameter of 6 mm and a thickness of 3.4 mm. The results of the 50% volume-based particle size (D50), 90% volume-based particle size (D90), disintegration time and tube passability test of the obtained magnesium oxide tablets after suspension in water are shown in Table 12.

[0061] Comparative Example 9 According to the formulation in Table 6, laxative tablets were manufactured. 1500g of magnesium oxide with a volume-based 50% particle size (D50) of 6.5 μm, 168g of crystalline cellulose, and 43.5g of croscarmellose sodium were mixed and granulated with a roll pressure of 5 MPa in a roll molding type dry granulator. The granulated material was pulverized with an oscillator type pulverizer to produce granules. To the obtained granules (1573g), 24.8g of insoluble polyvinylpyrrolidone 1 with a volume-based 50% particle size (D50) of 5.4 μm by laser diffraction method, 16.5g of calcium stearate, 35.8g of crystalline cellulose, 1.4g of aspartame, and 2.8g of acesulfame potassium were added, and mixed in a container type mixer to produce tablet granules. The obtained tablet granules were tableted under the same conditions as in Example 1 to obtain magnesium oxide tablets each weighing 120 mg, with a diameter of 6 mm and a thickness of 3.4 mm. The results of the 50% volume-based particle size (D50), 90% volume-based particle size (D90), disintegration time and tube passability test of the obtained magnesium oxide tablets after suspension in water are shown in Table 12.

[0062] Comparative Example 10 According to the formulation of Table 6, laxative tablets were manufactured. 1500g of magnesium oxide having a volume-based 50% particle size (D50) of 6.5 μm, 103.5g of crystalline cellulose, 49.5g of croscarmellose sodium, and 33g of corn starch were mixed and granulated in a roll molding type dry granulator at a roll pressure of 5 MPa. The granulated material was pulverized in an oscillator type pulverizer to produce granules. 17g of calcium stearate was added to 1543.2g of the obtained granules, and mixed to obtain tablet granules. The obtained tablet granules were tableted under the same conditions as in Example 1 to obtain magnesium oxide tablets weighing 113.6 mg per tablet, with a diameter of 6 mm and a thickness of 3.4 mm. Table 12 shows the volume-based 50% particle size (D50), volume-based 90% particle size (D90), disintegration time, and tube passability test results for the obtained magnesium oxide tablets after suspension in water. The formulation of Comparative Example 10 is based on the proportions of each agent in Example 1 and Formulation Example 1 of Patent Document 3.

[0063] [Table 1]

[0064] [Table 2]

[0065] [Table 3]

[0066] [Table 4]

[0067] [Table 5]

[0068] [Table 6]

[0069] [Table 7]

[0070] [Table 8]

[0071] [Table 9]

[0072] [Table 10]

[0073] [Table 11]

[0074] [Table 12]

[0075] From Tables 1 to 12 above, it can be seen that the laxative tablet of the present invention has a suspended particle size D50 of 70 μm or less, a suspended particle size D90 of 130 μm or less, a disintegration time of 10 seconds or less, and no blockage occurs in the 3Fr tube passability test. [Industrial Applicability]

[0076] The laxative tablet of the present invention has a fine particle size when suspended in water and disintegrates in a short time. When administering the tablet through a tube to a patient, particularly a child, the tablet can be disintegrated and suspended in water, allowing for smooth administration without clogging a thinner tube than before. In addition, the tablet disintegrates quickly in the oral cavity, reducing the burden on the patient when taking the tablet.

Claims

1. A laxative tablet containing magnesium oxide, The internal additive is the core, and the external additives are around it. the internal additive is a granule containing the magnesium oxide, first microcrystalline cellulose, croscarmellose sodium, and insoluble polyvinylpyrrolidone; The external additives include a second microcrystalline cellulose and a lubricant, In the tablet, the content of the magnesium oxide is 80 to 96% by weight, the content of the insoluble polyvinylpyrrolidone is 0.5 to 3.5% by weight, and (1) The particles generated when the tablet is suspended in water have a volume-based 50% particle diameter (D ５０ ) 70 μm or less, (2) The particles generated when the tablet is suspended in water have a volume-based 90% particle diameter (D ９０ ) 130 μm or less, (3) A tablet for use in children, which is administered through a feeding tube smaller than 8 Fr when suspended in water.

2. A laxative tablet containing magnesium oxide, The internal additive is the core, and the external additives are around it. the internal additive is a granule containing the magnesium oxide, the first microcrystalline cellulose, and an insoluble polyvinylpyrrolidone; The external additives include croscarmellose sodium, second microcrystalline cellulose, and a lubricant; In the tablet, the content of the magnesium oxide is 80 to 96% by weight, the content of the insoluble polyvinylpyrrolidone is 0.5 to 3.5% by weight, and (1) The particles generated when the tablet is suspended in water have a volume-based 50% particle diameter (D ５０ ) 70 μm or less, (2) The particles generated when the tablet is suspended in water have a volume-based 90% particle diameter (D ９０ ) 130 μm or less, (3) A tablet for use in children, which is administered through a feeding tube smaller than 8 Fr when suspended in water.

3. The tablet for use in children according to claim 1 or 2, wherein the lubricant comprises at least one of stearic acid and its Na salt, Mg salt, and Ca salt.

4. A tablet as described in claim 1 or claim 2, further comprising at least one sweetener selected from aspartame, acesulfame potassium, and sucralose.

5. A tablet according to claim 1 or claim 2, wherein the insoluble polyvinylpyrrolidone has a volume-based 50% particle diameter (D50) measured by a laser diffraction method of 15 μm or less.

Images