Method of tableting medium

Abstract

To make a tablet from a medium for providing significant convenience in use, management and storage, since prior powder medium cannot be stored for long term due to complication of measurement, error of measurement, scattering, and becoming damp since opening of a bottle or bag, in use of powder medium.SOLUTION: The powder which is a medium is configured so that, because of the property of the powder, by adding a filler and a lubricant to the powder, a composition of the powder is changed. Even the medium powder is supplied to a tablet making machine as it is, productivity cannot be improved and various tablet making failures occur, so that, making a tablet from medium is difficult, however, a tablet is made from the powder by adjusting grain size of powder, moisture value of powder, pre-pressure, main pressure in tablet making time, and a rotation number of the tablet making machine, therefore significant convenience can be exhibited in use, management and storage of the medium. In addition, the medium formed into the tablet is packaged by TPT package or individually packaged for achieving long term storage without affecting other tablet in halfway of use.

Description

[Technical field]

[0001] The present invention provides a powder medium that is prepared by compression molding and tableting without adding existing excipients or lubricants, with enhanced lubricity and adhesion, and suppressed capping, lamination, sticking, and binding, and provides tablets obtained from the powder by a compression molding machine and a tablet press. The present invention also provides a method of forming and tableting that allows stable production to be continued without causing any trouble when feeding the medium to the compression molding machine and the tablet press. The obtained tablets are also characterized by having a foaming feel and good disintegration properties. [Background technology]

[0002] In order to stably produce tablets using a compression molding machine and a tablet press, excipients and lubricants are added to reduce friction between the powder and the tablet press, and the tableting problems of capping, lamination, sticking, and binding are avoided. It is common to adjust the amount of additives to enable tableting under favorable conditions. Tableting without adding excipients and lubricants results in low productivity and tablet strength, leading to tablet breakage. In addition, when it comes to culture media, the composition is changed when excipients and lubricants are added, which impairs their role and makes them unusable. However, using the powder as is has various problems, such as the hassle of measuring, measuring errors, inconvenience of storage, and the inability to store the bottle or bag for a long time after opening. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] JP 2004-329155 A [Patent Document 2] Patent Application No. 2007-129976 [Patent Document 3] Patent Application No. 2008-290145 Summary of the Invention [Problem to be solved by the invention]

[0004] Culture media have problems such as the hassle of measuring, scattering, spilling, and the inability to store for long periods after opening. In addition, when compressing and tableting culture media, if excipients and lubricants are not added, the lubrication and adhesion are poor, and capping, lamination, sticking, and binding occur, resulting in low tableting productivity or making it impossible to tablet, so they have been avoided. Also, due to the nature of culture media, adding excipients and lubricants to the ingredients changes the composition and deviates from its role, so it has not been tableted. [Means for solving the problem]

[0005] When the medium is compressed and tableted, the particles and moisture content of the powder are adjusted to enhance the lubricity and binding of the powder without adding existing excipients or lubricants, and stable production is continued without any trouble when feeding the powder to the compression molding machine and tablet press.Furthermore, by adjusting the pressurization, main pressure, and tableting speed of the tablet press, capping, lamination, sticking, and binding are suppressed, and tablets obtained through stable production are provided.Furthermore, the tablets obtained by the present invention are characterized by having a fizzy feeling and disintegrating. Effect of the Invention

[0006] In the present invention, the devices for forming tablets include compression forming machines (e.g., Rakugan forming machines), rotary type tablet presses, direct-acting types (motor-driven), and eccentric types (reciprocating types). Compression forming machines are easier to form when the powder is moist, and can compress and form tablets with a high moisture content. Compared to the rotary type, the eccentric type and direct-acting types have a slower tableting speed, but they can form tablets if the pre-pressure and main pressure can be adjusted. In addition, the ease of tableting and commercial production volume are higher with rotary type tablet presses, but it is not possible to simply compare the ease of tableting between the two. Therefore, it is necessary to select a compression forming machine and a tablet press that are suitable for the powder.

[0007] Since rotary tablet presses press tablets at high speed, it is difficult to expel the air that was present in the powder during tableting, and if no excipients or lubricants are added, the mutual adhesion of the powder particles is insufficient, which easily leads to capping, where the top of the tablet peels off like a hat, and lamination, where the middle part of the tablet peels off in layers. However, if all the air in the tablet is expelled, the disintegration properties will deteriorate, so this invention provides a tablet that has a foaming feeling and disintegrates when dropped into water by adjusting two stages of pre-pressure and main pressure so that air remains in the tablet.

[0008] When a powder medium is tableted using a compression molding machine or a rotary tablet press without adding any excipients or lubricants, the rotation speed of the rotary tablet press is controlled to prevent capping, lamination, and binding, the raw material powder is adjusted to a particle size of 3 to 800 microns suitable for tableting, preferably to a uniform particle size, a part of the powder is made into a fine powder, or the entire powder is made into a fine powder, and the powder is fed to the compression molding machine and the tablet press to be tableted.The present invention provides a tablet that has a foaming feeling and disintegrates when dropped into water.

[0009] The medium powder is pulverized using a roller mill, jet mill, planetary ball mill, rotary mill, vibration mill, pin mill, hammer mill, attritor, or bead mill to obtain a powder with a particle size of 3 to 800 μm, preferably 10 to 300 μm, and the powder is then fed to a compression molding machine and a tablet press to obtain tablets.

[0010] When tableting a powder medium, the moisture content is appropriately selected from a constant temperature dryer, constant temperature dryer, low temperature dryer, drum dryer, fluidized bed dryer, vibrating fluidized dryer, flash dryer, hot air dryer, vacuum dryer, drum dryer dryer, stirring dryer, nitrogen dryer, and desiccator dryer, and the powder with the adjusted moisture content is supplied to a compression molding machine and a tableting machine to obtain tablets.

[0011] The drying device for drying the BGLB medium, which is an example of a medium containing an indicator, is appropriately selected from a constant temperature dryer, a constant temperature dryer, a low temperature dryer, a drum dryer, a fluidized bed dryer, a vibration fluidized dryer, a flash dryer, a hot air dryer, a vacuum dryer, a drum dryer dryer, an agitator dryer, a nitrogen dryer, and a desiccator dryer. As an example, if the BGLB medium is dried at a drying temperature of 60°C or higher, the brilliant green is damaged and a pigment change that causes a slight yellowish tinge occurs, so a temperature of 60°C or lower is more preferable.

[0012] As an example of bouillon medium powder, if BGLB powder medium is fed directly to a tablet press, the powder flow is poor, the weight of the completed tablets is unstable, and tableting problems such as capping, lamination, sticking, and binding occur. This is because the moisture content of the bouillon powder is high, which causes lumps to form in the powder and makes the particle size inconsistent. Here, we searched for a moisture content suitable for tableting and obtained tablets by continuous tableting with a stable moisture content of 1.7 to 4.2%, more preferably 2.1 to 2.7%. In addition, we provide tablets obtained by drying or pouring the lumps formed in the powder to return it to its original particle size, and feeding the powder adjusted to a particle size of 1.1 to 300 μm, more preferably 8 to 150 μm, to a compression molding machine and a tablet press.

[0013] When the powder particle size of a standard agar medium, which is an example of a medium containing agar, is measured, it is divided into a bouillon portion and an agar portion with an unstable particle size. The particle size of the bouillon portion is about 0.3 to 60 μm, and the agar portion is about 6 to 400 μm. The particle size of this agar portion is adjusted to 0.3 to 300 μm, more preferably 10 to 200 μm. Furthermore, the moisture value is adjusted to 2.0 to 5.5%, more preferably 2.5 to 3.3%. The moisture value of the bouillon portion of this powder is adjusted to 2.7 to 5.0%, more preferably 2.1 to 3.2%. At this time, if the agar portion is overdried, it loses its binding property when compressed and tableted, so it is not suitable for tableting.

[0014] When the particle size of the powder of desoxycholate medium, which is an example of a medium containing agar, is measured, it is separated into a bouillon portion and an agar portion with an unstable particle size. The particle size of the bouillon portion is about 0.4 to 200 μm, and the agar portion is about 6 to 400 μm. The particle size of this agar portion is adjusted to 0.3 to 300 μm, more preferably 10 to 200 μm, and the moisture content is 2.5% to 5.5%, more preferably 2.5% to 3.5%. The moisture content of the bouillon portion is 2.7 to 5.0%, more preferably 2.1 to 3.2%. At this time, if the agar portion is overdried, it loses its binding property when compressed and tableted, so it is not suitable for tableting.

[0015] The drying temperature for the powdered bouillon portion of the medium is 35 to 60°C, more preferably 40 to 45°C, and is appropriately selected from a constant temperature dryer, constant temperature dryer, low temperature dryer, drum dryer, fluidized bed dryer, vibrating fluidized dryer, air flow dryer, hot air dryer, vacuum dryer, drum dryer dryer, stirring dryer, nitrogen drying, and desiccator drying.

[0016] The tablet shape of the medium is appropriately selected from round, triangular, rectangular, pentagonal, hexagonal, octagonal, elliptical, rugby ball-shaped, cylindrical, or layered tablets according to the intended purpose and shape of use.

[0017] The tablets are individually wrapped and packed in PTP packages so that they do not affect other tablets that are in use, and when using large quantities, they can be transferred to pillow-packaged or cartridge-type special containers for long-term storage. EXAMPLES

[0018] The medium had problems such as the trouble of measuring the amount of the medium when using it, measurement errors, scattering, and the fact that the medium becomes damp after opening the bottle or bag, making it impossible to store it for a long time. Also, even if the medium powder is directly fed into a compression molding machine or tablet press, productivity is low and various tableting problems such as capping, lamination, sticking, and binding occur. In order to tablet the medium with high productivity, the following experiment was carried out. The medium was tableted. The graphs in Figures 1 and 2 below are particle size measurement graphs of the BGLB medium without any preparation. The powder in Figure 1 had a particle size distribution of about 1.7 to 152 μm, an average particle size of about 22.7 μm, and a moisture value of about 3.3%. In the process of feeding this powder to a rotary tablet press, the fluidity of the powder was somewhat poor, making it difficult to obtain a constant mass in the tablets, and binding occurred on the side of the tablets. In addition, when the powder was dried in a constant temperature dryer at 55 to 60 ° C for 10 hours to reduce the moisture value to 2.7%, and then fed to the rotary tablet press again, the fluidity was improved and tablets were successfully obtained. However, the liquid obtained by putting the compressed BGLG tablets into water and sterilizing at 121 ° C for 15 minutes was a slightly yellowish liquid compared to the aqueous solution obtained by putting a normal BGLB powder medium into water and sterilizing at 121 ° C for 15 minutes. (Figure 9) The phenomenon that the BGLB solution becomes slightly yellowish occurs when sugar is decomposed and generates acid, or when the water used is acidic. However, it is unlikely that sugar is decomposed and becomes acidic during drying, so we speculated that the temperature during drying damaged the Brilliant Green. Therefore, the powder in Figure 1 was dried in a thermostatic dryer at 40-45°C for 12 hours and the moisture content was adjusted to 2.9%, which eliminated the binding on the tablet side and led to continuous tableting. In addition, unprepared BGLB powder medium was added to water, and BGLB tablets with moisture content adjusted at 40-45°C and 55-60°C were sterilized at 121°C for 15 minutes. The aqueous solution obtained was measured with a spectrophotometer. (Figure 10) The pH of this aqueous solution was within the control range of 7.2 ± 0.3. The particle size distribution of the powder in Figure 2 was about 11 to 3000 μm, the average particle size was about 430 μm, and the moisture content was about 3.4%. In the process of feeding this powder to a rotary tablet press, the powder had poor fluidity, and not only was it not possible to obtain a consistent tablet mass, but capping and lamination occurred. When the powder was dried in a thermostatic dryer at 40-45°C for 12 hours to bring the moisture content to approximately 2.7%, and then fed to the rotary tablet press again, the fluidity improved somewhat, but the compressed tablets were somewhat brittle. Figure 1

[0019] TIFF0007618935000001.tif68156 Figure 2

[0020] TIFF0007618935000002.tif66150

[0021] The graphs in Figures 3 and 5 are particle size measurement graphs of desoxycholate medium without any preparation. The particle size distribution in Figure 3 was about 0.76 to 300 μm, the average was about 46.6 μm, and the moisture value was about 4.3%. In the process of feeding this powder to a rotary tablet press, the fluidity was poor, and tablets were not formed due to the occurrence of capping and lamination. Figure 4 shows the powder in Figure 3 finely ground, with a particle size distribution of about 2.5 μm to 174 μm, an average particle size of about 24.7 μm, and the powder was dried in a thermostatic dryer at 40 to 45 ° C for 12 hours to adjust the moisture value to about 3.2%. In the process of feeding this powder to a rotary tablet press, the fluidity was better than that of the powder in Figure 3, and a certain mass was obtained in the tablets, but capping and lamination were observed. In addition, the powder was dried in a thermostatic dryer at 50-55°C for 12 hours to a moisture content of about 2.9%, and the powder was then fed again to a rotary tablet press. The flowability was improved, but the agar was overdried and became sandy, and it could no longer function as a binder during tableting. The particle size distribution in Figure 5 was about 6-400 μm, with an average particle size of about 81 μm and a moisture content of about 4.2%. In the process of feeding this powder to a rotary tablet press, the flowability was improved and tablets were obtained, but capping and lamination occurred during the process. In addition, the aqueous solutions of the tablets in Figures 3, 4, and 5 and the solution obtained from the normal desoxycholate powder were measured with a spectrophotometer. (Figure 9) The pH of these solutions conformed to the standard of 7.2 ± 0.3. Figure 3

[0022] TIFF0007618935000003.tif61148Figure 4

[0023] TIFF0007618935000004.tif64148 Figure 5

[0024] TIFF0007618935000005.tif65143

[0025] FIG. 6 is a graph showing the particle size measurement of a standard agar medium without any preparation. The particle size distribution in FIG. 6 was about 7.1 to 340 μm, with an average of about 131 μm, and a moisture value of about 3.75%. In the process of feeding this powder to a rotary tablet press, the fluidity was poor and almost no tablets were formed. The particle size distribution in FIG. 7 was about 0.5 to 260 μm, with an average of about 47.5 μm, and a moisture value of about 3.3%. In the process of feeding this powder to a rotary tablet press, the fluidity was slightly better than that of the powder in FIG. 6, but few tablets were obtained because capping and lamination occurred during tableting. FIG. 8 shows the powder in FIG. 7 finely ground, adjusted to a particle size distribution of about 0.25 μm to 10 μm and an average particle size of about 3.2 μm, and the powder was dried in a thermostatic dryer at 40 to 45° C. for 12 hours and adjusted to a moisture value of about 3.2%. In the process of feeding this powder to a rotary tablet press, the fluidity was better than that of the powders in Figures 6 and 7, and a certain mass was obtained for the tablets, but capping and lamination were observed in the tablets that were compressed. In addition, the same powder was dried in a constant temperature dryer at 50-55°C for 12 hours to adjust the moisture content to about 2.9%, and in the process of feeding this powder to a rotary tablet press, the fluidity was further improved, but the agar part was overdried and became sandy, and it no longer served as a binder during tableting. In addition, the number of tablets obtained was small due to the occurrence of capping and lamination. The particle size distribution in Figure 9 was about 2-10 μm, the average particle size was about 3.2 μm, and the moisture content was about 4.2%. In the process of feeding this powder to a rotary tablet press, the fluidity was good and tablets were obtained, but capping and lamination were observed in the tablets that were compressed. In addition, the tablets and powder of the standard agar medium obtained in Figures 6 to 9 were added to water and dissolved by heating, sterilized at 121°C for 20 minutes, and cooled in a constant temperature bath at 45 to 50°C. The resulting solutions were measured with a spectrophotometer (Figure 10). The pH of these solutions also fell within the control range of 7.1±0.2. Figure 6

[0026] TIFF0007618935000006.tif70153 Figure 7

[0027] TIFF0007618935000007.tif65154 Figure 9

[0028] TIFF0007618935000008.tif68155

[0029] In Figure 10, 1 to 3 indicate untreated powdered media, 4 indicates a comparison product, and tablets were dried in a thermostatic dryer at 40°C and 60°C and pressed into tablets, which were then used as agar media, BGLB was heated at 121°C for 20 minutes, and desoxycholate media was dissolved by heating, and then adjusted to 45 to 50°C in a thermostatic chamber, after which they were measured with a spectrophotometer. Figure 10 TIFF0007618935000009.tif106157

[0030] The moisture content of the bouillon portion of each medium was adjusted to 1.5 to 6.5%, preferably 2 to 3%, and the agar portion was finely pulverized to 10 to 200 μm, preferably 10 to 100 μm, with a moisture content of 1.5 to 6.5%, preferably 2.5 to 3.7%, and the powder was then fed into a rotary tablet press, which successfully improved fluidity and produced tablets.

[0031] The implementation and preparation methods are shown above, but are not limited thereto. [Industrial Applicability] The present invention solves the problems of the trouble of measuring, measuring errors, scattering, and the inability to store the medium for a long time due to moisture after opening the bottle or bag, which may occur when using the medium, by tableting the powder of the medium, making it possible to count the quantity and making it visible, thereby solving the trouble of measuring and errors. In addition, even if the medium powder is directly fed to the tablet press, the productivity is low and various tableting problems such as capping, lamination, sticking, and binding occur, but the method is to adjust the particle size and moisture value of the medium powder without adding existing excipients and lubricants, and further adjust the tableting pressure by adjusting the pre-pressure, main pressure, and rotation speed of the tablet press, and tablet it with a compression molding machine and a tablet press to produce tablets. In addition, the disintegration property is improved by deliberately leaving air in the tablet. The present invention has the potential to demonstrate outstanding convenience in the use, management, and storage of the medium in the future.

Claims

[Claim 1] A method for producing tablets of a powdered medium, comprising drying a BGLB powdered medium having a particle size distribution of 1.7 to 152 μm and an average particle size of 22.7 μm in a thermostatic dryer at 40 to 45° C., adjusting the moisture content to 2.9%, and tableting the medium with a rotary tablet press.

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