Porous Sorbitol

Abstract

To provide a sorbitol that can provide a tablet having sufficient hardness by direct tableting under low tableting pressure.SOLUTION: A porous sorbitol has a specific surface area of 5.0 m2 / g or more by BET one-point method, and a pore volume of 0.45 ml / g or more by mercury press-in method.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to porous sorbitol suitable for direct compression. [Background technology]

[0002] Sorbitol has traditionally been used as a sweetener and excipient in the food and pharmaceutical fields.

[0003] Generally available sorbitol powder is a crystalline powder, and therefore has a problem of weak binding strength. For example, when used in tablets, it easily disintegrates after molding. Therefore, when used for such purposes, a method called granule compression is used, in which sorbitol powder is granulated and then compressed into tablets. However, the granule compression method has the problem of complicated manufacturing processes and increased manufacturing costs.

[0004] Furthermore, in the production of tablets, tableting must be carried out at a certain pressure or higher, but high pressure places a heavy burden on the tablet press body and molds, so tableting tends to be carried out at as low a pressure as possible.

[0005] However, tableting at low pressure has the problem that tableting problems such as picking and sticking, in which part or all of the resulting tablets break off and adhere to the punches, are likely to occur.

[0006] Patent Document 1 describes a method for producing a sorbitol solution by hydrogenating a glucose-containing solution, and spray-drying the sorbitol solution to produce a sorbitol having a specific surface area of ​​0.7 to 1.5 m. 2 The paper describes a method for producing a modified sorbitol having a tableting property of 0.1g / g. However, when tableting sorbitol having such a specific surface area, it is necessary to apply a certain amount of pressure to the tablet press, and if the pressure is too high, a large burden is placed on the tablet press body and the mold.

[0007] Patent Document 2 describes a sugar alcohol granule for direct compression processing, which is obtained by charging sugar alcohol powder into a centrifugal tumbling granulation coating device, spraying a sugar alcohol solution onto it, and then drying it in a fluidized bed granulation coating device. However, as mentioned above, the granule compression method of tableting after granulation has the problem of complicating the manufacturing process and increasing manufacturing costs.

[0008] Patent Document 3 describes a sorbitol granulator having a specific surface area of ​​2.5 to 3.5 m, which is obtained by concentrating sorbitol in an air fluidized bed granulator and spraying a sorbitol solution onto the sorbitol melt. 2 / g of granulated sorbitol is described, but it is difficult to say that tablets having sufficient hardness can be produced even when compressed at low pressure, and the production process is also complicated.

[0009] Therefore, there has been a demand for sorbitol that can be formed by direct tableting without requiring a granulation step or complicated manufacturing steps, and that can be used to produce tablets with sufficient hardness even when compressed at low pressure. [Prior art documents] [Patent documents]

[0010] [Patent Document 1] Japanese Patent Application Publication No. 59-118058 [Patent Document 2] Japanese Patent Application Laid-Open No. 2001-10979 [Patent Document 3] Special Publication No. 2009-544674 Summary of the Invention [Problem to be solved by the invention]

[0011] An object of the present invention is to provide sorbitol that can provide tablets having sufficient hardness through direct compression with low tableting pressure. [Means for solving the problem]

[0012] As a result of extensive investigation, the inventors have found that the specific surface area by the BET (Brunauer-Emmett-Teller) single point method is 5.0 m 2 / g or more and a pore volume measured by mercury porosimetry of 0.45 ml / g or more can solve the above problems, and the present invention has been completed based on this finding.

[0013] That is, the present invention is a method for producing a cellulose fiber having a specific surface area of ​​5.0 m2 by the BET single point method. 2 / g or more and a pore volume measured by mercury porosimetry of 0.45 ml / g or more. DETAILED DESCRIPTION OF THE INVENTION

[0014] The present invention will be described in detail below.

[0015] The specific surface area of ​​the porous sorbitol of the present invention is 5.0 m 2 / g or more, preferably 6.0 to 50.0m 2 / g, more preferably 7.0 to 30.0 m 2 / g.

[0016] The specific surface area referred to in the present invention means a value measured by the BET single-point method using, for example, a MONOSORB (manufactured by Yuasa Ionics Co., Ltd.) or an equivalent specific surface area measuring device. For example, the specific surface area can be measured under the following measurement conditions. [Measurement conditions] Method: BET style one point method Carrier gas: N2: 30% + He: 70% Measurement gas flow rate: 15cc / min Degassing conditions: 60°C, 20 minutes

[0017] The pore volume of the porous sorbitol of the present invention is 0.45 ml / g or more, preferably 0.50 to 3.00 ml / g, and more preferably 0.55 to 2.50 ml / g.

[0018] The pore volume referred to in the present invention means a value measured by mercury intrusion porosimetry using, for example, a Pascal 240 (manufactured by Thermo Fisher Scientific) or an equivalent pore volume measuring device.

[0019] The average particle size of the porous sorbitol of the present invention is preferably from 1 to 600 μm, more preferably from 20 to 550 μm, and even more preferably from 30 to 500 μm.

[0020] The uniformity of the porous sorbitol of the present invention is preferably 5.00 or less, more preferably 4.80 or less, and even more preferably 0.40 to 4.60.

[0021] The average particle size and uniformity of the porous sorbitol are values ​​measured using a laser diffraction particle size distribution analyzer (Mastersizer (registered trademark) 3000, manufactured by Malvern Instruments). Unless otherwise specified, the average particle size in the present invention refers to the cumulative 50% particle size (D50) in the particle size distribution measured by laser diffraction.

[0022] The angle of repose of the porous sorbitol of the present invention is preferably 25 to 50°, more preferably 26 to 48°, and even more preferably 27 to 47°. If the angle of repose is less than 25°, scattering tends to increase, while if it exceeds 50°, the flowability of the porous sorbitol tends to decrease, making it difficult to handle.

[0023] The degree of compression of the porous sorbitol of the present invention is preferably 10 to 45%, more preferably 13 to 43%, and even more preferably 15 to 40%. If the degree of compression is less than 10%, the porous sorbitol tends to be more dispersible, while if it exceeds 45%, the porous sorbitol tends to have poor fluidity and poor handleability. The degree of compression is a numerical value calculated by the following formula. Compressibility (%) = [Packed bulk density (g / cm 3 ) - Loose bulk density (g / cm 3 )] / packed bulk density (g / cm 3 ) x 100

[0024] The loose bulk density and packed bulk density of the porous sorbitol of the present invention are preferably 0.10 to 0.45 g / ml and 0.15 to 0.55 g / ml, and more preferably 0.12 to 0.40 g / ml and 0.20 to 0.50 g / ml.

[0025] The angle of repose, loose bulk density and packed bulk density are values ​​measured using a powder tester (PT-X, manufactured by Hosokawa Micron Corporation).

[0026] Porous sorbitol exhibiting such physical properties can be produced, for example, by kneading molten sorbitol with ethanol, followed by drying under reduced pressure. In one preferred embodiment, the method for producing porous sorbitol of the present invention comprises the following steps: a) feeding molten sorbitol and ethanol into a kneading device; b) kneading molten sorbitol and ethanol in a kneading device while maintaining the temperature at 50 to 78°C; and c) A step of removing ethanol by drying the kneaded mixture obtained in b) at 25 to 90°C and under reduced pressure of 100 to 30,000 Pa. The method includes:

[0027] The above production method will now be described in more detail. First, in step a), 10 to 70 parts by weight of molten sorbitol and 30 to 90 parts by weight of ethanol are fed into a kneading device. The amounts fed into the kneading device are preferably 15 to 68 parts by weight of molten sorbitol and 32 to 85 parts by weight of ethanol, and more preferably 20 to 65 parts by weight of molten sorbitol and 35 to 80 parts by weight of ethanol. If the amount of ethanol fed exceeds 90 parts by weight, the physical properties of the kneaded product of sorbitol and ethanol tend to deteriorate, and production efficiency tends to decrease. If the amount of ethanol fed is less than 30 parts by weight, the specific surface area of ​​the porous sorbitol produced tends to decrease.

[0028] The amount of water contained in the ethanol used in step a) is, for example, 10% by weight or less. The amount of water contained in the ethanol is preferably 8% by weight or less, more preferably 5% by weight or less, even more preferably 2% by weight or less, and particularly preferably 0% by weight (ethanol only). The lower the amount of water contained in the ethanol, the higher the specific surface area of ​​the porous sorbitol produced tends to be. If the amount of water contained in the ethanol is 20% by weight or more, the amount of sorbitol that dissolves in water increases, which reduces the specific surface area of ​​the porous sorbitol produced, making it difficult to make the sorbitol porous in steps b) and c), which will be described later.

[0029] Next, in step b), the molten sorbitol and ethanol are kneaded in a kneading device while maintaining the temperature at 50 to 78°C. By maintaining the temperature in the kneading device at 50 to 78°C, the molten sorbitol and ethanol can be kneaded without rapid solidification of the molten sorbitol in the kneading device and while suppressing the evaporation of the ethanol. The temperature in the kneading device is preferably 55 to 78°C, and more preferably 60 to 75°C. If the temperature in the kneading device is less than 50°C, the mixture tends to be difficult to form porous particles, and if the temperature exceeds 78°C, the ethanol tends to evaporate easily.

[0030] In step c), the kneaded mixture obtained in step b) is dried under reduced pressure at 25 to 90°C and 100 to 30,000 Pa to remove ethanol, thereby obtaining porous sorbitol. The reduced-pressure drying is carried out using a reduced-pressure dryer such as an evaporator. When drying is carried out under normal pressure in step c), the specific surface area of ​​the porous sorbitol tends to decrease. Furthermore, when drying is carried out at a temperature above 90°C, the specific surface area and pore volume of the sorbitol produced by melting the sorbitol tend to decrease. The porous sorbitol obtained in step c) may be pulverized or sized using a blender or the like.

[0031] As the kneading device used in the production of the porous sorbitol described above, kneading machines such as a vertical kneader, a horizontal batch kneader, and a KRC kneader are used.

[0032] A horizontal batch kneader is preferred from the standpoints of production efficiency and quality because, when molten sorbitol and ethanol are kneaded together in the above-mentioned porous sorbitol production process b), the molten mixture can be crystallized in a short time, and the porous sorbitol obtained through process c) exhibits a high specific surface area and pore volume.

[0033] The KRC kneader is preferable from the viewpoints of productivity and economy because it can crystallize the molten kneaded product in a very short time when molten sorbitol and ethanol are kneaded in the above-mentioned porous sorbitol production process b).

[0034] The porous sorbitol of the present invention can be used in a variety of fields, such as food and beverages, cosmetics, quasi-drugs, and pharmaceuticals, and because it has a large specific surface area and pore volume, it can provide tablets with sufficient hardness by direct tableting at low tableting pressure without pretreatment such as granulation.

[0035] The porous sorbitol of the present invention can also be used as an excipient or texturing agent for producing tablets such as pharmaceutical tablets, supplement tablets, and tablet candies, and even when mixed with other tablet ingredients such as lubricants, functional ingredients such as pharmaceutically active ingredients, and nutritional ingredients such as food ingredients and compressed by direct compression, the resulting tablets have strong binding strength and high tablet hardness. Furthermore, when producing tablets using the porous sorbitol of the present invention, no special equipment or facilities are required, and a conventionally commonly used single-shot or continuous tablet press can be used. By using the porous sorbitol of the present invention, tableting is possible at a low tableting pressure, for example, 0.20 to 0.40 kN.

[0036] Tablets produced using the porous sorbitol of the present invention vary depending on the size, weight and compression pressure of the tablet, but for example, the tablet hardness at a compression pressure of 0.25 kN is 80 N or more, preferably 82 to 180 N, more preferably 85 to 170 N, and the tablet hardness at a compression pressure of 0.33 kN is 100 N or more, preferably 105 to 220 N, more preferably 110 to 210 N.

[0037] The tablet hardness referred to in the present invention means a value measured using, for example, a Kiya type digital hardness tester (KHT-20N, manufactured by Fujiwara Seisakusho Co., Ltd.) or an equivalent hardness measuring device.

[0038] The amount of the porous sorbitol of the present invention used in the production of tablets is not particularly limited and may be adjusted appropriately depending on the purpose. The content of the porous sorbitol in the tablet components is, for example, 20 to 99 wt %, preferably 50 to 99 wt %.

[0039] A lubricant may be added when producing tablets using the porous sorbitol of the present invention. Usable lubricants are not particularly limited, and include common ones designated as food additives, such as sucrose fatty acid esters, calcium stearate, magnesium stearate, and glycerin fatty acid esters. Among these, sucrose fatty acid esters, calcium stearate, and magnesium stearate are preferred because of their excellent lubricity. The amount of lubricant is not particularly limited and may be adjusted appropriately depending on the purpose of the tablet. However, in terms of tablet hardness, the amount is preferably 10% by weight or less, and more preferably 0.1 to 5% by weight.

[0040] Tablets produced using the porous sorbitol of the present invention may be food products such as candy tablets and supplement tablets, and examples thereof include candy tablets and supplement tablets with flavors such as mint and fruit, and those having functions of preventing bad breath and tooth decay. Candy tablets may be licked or chewed to enjoy the taste.

[0041] Tablets produced using the porous sorbitol of the present invention may be blended with other food ingredients. The food ingredients are not particularly limited, and for example, ingredients that have traditionally been used as ingredients for tablet confectionery can be used without any restrictions. Examples of food ingredients include dried bean paste, powdered tea, powdered fruit juice, and dried fruit.

[0042] The tablet produced using the porous sorbitol of the present invention may be a pharmaceutical tablet. There is no particular limitation on the pharmaceutically active ingredient used in the pharmaceutical tablet, and for example, any ingredient that has been conventionally used in pharmaceutical tablets may be used. The pharmaceutical tablet provided by the present invention may contain a single pharmaceutically active ingredient or a combination of two or more ingredients.

[0043] The amount of a pharmaceutically active ingredient contained in a pharmaceutical tablet produced using the porous sorbitol of the present invention may be determined appropriately based on the type of ingredient, the disease to be treated, the age and weight of the patient to be treated, the treatment period, the desired therapeutic effect, etc.

[0044] Tablets produced using the porous sorbitol of the present invention may further contain one or more additives. The additives to be added during tableting are not particularly limited, and any additives conventionally used in tablets can be added. Examples of additives include disintegrants such as crystalline cellulose, crystalline cellulose derivatives, and modified starches, binders such as pregelatinized starch and pullulan, excipients other than sugar alcohols such as lactose, sucrose, and glucose, flavorings, colorants, and acidulants. The amount of additive added is determined appropriately depending on the desired properties of the tablet.

[0045] The amount of ingredients other than porous sorbitol and lubricants in tablets produced using the porous sorbitol of the present invention is, for example, 79.9% by weight or less, and preferably 0.1 to 50% by weight.

[0046] Furthermore, the porous sorbitol of the present invention can be used to stabilize useful substances or as a powder base for perfumes and oily substances, taking advantage of its physical property of having a large number of pores.

[0047] The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples in any way. [Example]

[0048] Examples 1 to 11 and Comparative Examples 1 to 9 The materials shown below were melt-kneaded in the proportions and under the conditions shown in Table 1, and the crystallized mixture was dried under reduced pressure using a rotary evaporator under the conditions shown in Table 1 to obtain porous sorbitol. The obtained porous sorbitol was pulverized at 15,700 rpm for 30 seconds using a blender shown below. The produced porous sorbitol, Sorbitol 1 and Sorbitol 2 shown below, were measured for specific surface area, pore volume, particle size distribution, uniformity, angle of repose, loose bulk density, packed bulk density, and tablet hardness. Note that in the above production, if the kneaded product did not crystallize during melt-kneading, the evaluation was terminated without carrying out the following measurements (Comparative Examples 4 to 9). <Material> Sorbitol 1: Powdered sorbitol "Ueno" 20M (Ueno Food Techno Co., Ltd., sorbitol purity 92%) Sorbitol 2: Partec® SI 150 (Merck, sorbitol purity 98.4%) Maltitol: Powdered maltitol "Ueno" 60M (manufactured by Ueno Food Techno Co., Ltd.) Xylitol: Grade 1 xylitol (reagent, manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) Ethanol 1: Grade 1 ethanol (reagent, Fujifilm Wako Pure Chemical Industries, Ltd., ethanol 99.5% by weight) Ethanol 2: Fermented ethanol (95% ethanol, manufactured by Daiichi Alcohol Co., Ltd., 92.3% by weight) Ion-exchanged water <Kneading equipment> Horizontal: Horizontal kneader (KC-6 type, manufactured by Satake Corporation) Vertical type: Vertical kneader (5NDM-Qr type, manufactured by Shinagawa Kogyosho Co., Ltd.) KRC: KRC kneader (S2 type, manufactured by Kurimoto Iron Works, Ltd.) Blender Blender (16-speed blender, Oster)

[0049] Specific surface area measurement The sorbitol powders obtained in the above Examples and Comparative Examples were placed in a measurement cell in an amount of about half the internal volume (0.1 to 1.0 g), and measurements were performed using a BET-type specific surface area meter (MONOSORB, manufactured by Yuasa Ionics Co., Ltd.) under the following conditions. The results are shown in Table 2. [Measurement conditions] Method: BET style one point method Carrier gas: N2: 30% + He: 70% Measurement gas flow rate: 15cc / min Degassing conditions: 60°C, 20 minutes

[0050] Pore ​​volume measurement The pore volume was measured using a mercury porosimeter (Pascal 240, manufactured by Thermo Fisher Scientific). The results are shown in Table 2.

[0051] Particle size distribution and uniformity measurement The average particle size and uniformity were measured using a laser diffraction particle size distribution analyzer (Mastersizer (registered trademark) 3000, manufactured by Malvern Instruments). The results are shown in Table 2.

[0052] Measurement of angle of repose, loose bulk density and packed bulk density Measurements were made using a powder tester (PT-X, manufactured by Hosokawa Micron Corporation). The angle of repose was measured using a sieve with 710 μm openings and a vibration time of 180 seconds. The loose bulk density was measured using a sieve with 710 μm openings. The sample was fed from directly above into a stationary 100 mL cylindrical container with an amplitude of 1.5 mm and an operating time of 30 seconds, the excess sample was leveled off, and the content was precisely weighed. The packed bulk density was the specific gravity after 180 tappings with a stroke width of 18 mm. The results are shown in Table 2.

[0053] Tablet hardness measurement The sorbitol powder obtained in the above Examples and Comparative Examples was mixed with calcium stearate (Kishida Chemical Co., Ltd.) at a lubricant ratio of 1% and placed in a tabletop rotary tablet press (PICCOLA B-10, manufactured by Estec Co., Ltd.) equipped with circular concave punches with a diameter of 8 mm and a radius of curvature of 12 mm. Tablets with a diameter of 8 mm, height of 3 mm, and weight of 0.15 g were produced at tableting pressures of 0.25 kN and 0.33 kN and a tableting speed of 10 rpm. Hardness measurements were performed using a Kiya-type digital hardness tester (KHT-20N, manufactured by Fujiwara Seisakusho Co., Ltd.) to measure the hardness of 10 tablets, and the average value was used to calculate the hardness. The results are shown in Table 2.

[0054] It was confirmed that the porous sorbitol of Examples 1 to 11 of the present invention had a higher specific surface area and pore volume than the powdered sorbitol of Comparative Examples 1 to 3, and had a higher tablet hardness when compressed at a low pressure.

[0055] [Table 1-1]

[0056] [Table 1-2]

[0057] [Table 2-1]

[0058] [Table 2-2]

Claims

1. Specific surface area measured by the BET single point method is 5.0 to 30.0 m ２ / g and a pore volume measured by mercury porosimetry of 0.45 to 2.50 ml / g.

2. 2. The porous sorbitol according to claim 1, having an average particle size of 1 to 600 μm.

3. 3. The porous sorbitol according to claim 1, wherein the degree of compressibility, calculated by the following formula, is 10 to 45%. Compressibility (%) = [Packed bulk density (g / cm ３ ) - loose bulk density (g / cm ３ ) / packed bulk density (g / cm ３ ) x 100

4. 4. The porous sorbitol according to claim 1, which has a loose bulk density of 0.10 to 0.45 g / ml and a packed bulk density of 0.15 to 0.55 g / ml.

5. a) feeding molten sorbitol and ethanol into a kneading device; b) kneading molten sorbitol and ethanol in a kneading device while maintaining the temperature at 50 to 78°C; and c) A step of removing ethanol by drying the kneaded mixture obtained in b) at 25 to 90°C and 100 to 30,000 Pa under reduced pressure. The specific surface area by the BET single point method is 5.0 to 30.0 m ２ / g and a pore volume measured by mercury porosimetry of 0.45 to 2.50 ml / g.

6. A tablet containing the porous sorbitol according to any one of claims 1 to 4.

7. The tablet according to claim 6, having a tablet hardness of 80 N or more.

8. A method for producing a tablet, comprising compressing tablet ingredients containing the porous sorbitol according to any one of claims 1 to 4.

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