JP6752927B2 - Manufacturing method of orally disintegrating tablets - Google Patents

Description

The present invention relates to orally disintegrating tablets, and in particular, by wet-granulating sugar or sugar alcohol with an ethyl cellulose solution and surface-modifying the tablet, high hardness can be obtained even with low-pressure tableting, and there is no tableting disorder. The present invention relates to an orally disintegrating tablet that can be applied to actual production and can suppress a decrease in hardness and a delay in disintegration even when stored for a long period of time.

Tablet-type formulations for delivering drugs into the body have long been convenient and useful.

However, not only are many people uneasy about swallowing tablets, but also elderly people with hand tremor and swallowing disorders, and because they cannot swallow tablets, they are given in the form of syrup or crushed into water. Infants and children who have to mix with and drink, when it is difficult to obtain water such as when traveling, patients with restricted fluid intake such as kidney disease patients, who are in a state of bedtime and get up to take drugs Tablets are still an inconvenient dosage form, such as for patients who have difficulty with.

An orally disintegrating tablet (Orally Disintegrating Tablet) has been developed to improve such inconvenience. Orally disintegrating tablets are in the form of tablets that can be taken without water by disintegrating the tablets in the oral cavity with saliva in a few seconds to several tens of seconds. Orally disintegrating tablets include Fast Disintegrating Tablets, Rapidly Melting Tablets, Orally Disintegrating Tablets, Fast Disintegrating Tablets, Fast Disintegrating Tablets, Fast Disintegrating Tablets, etc. Called by various names.

Sugars, sugar alcohols and the like are used as the main excipients for such orally disintegrating tablets. However, since sugars or sugar alcohols do not have good tableting properties, when they are used as the main excipient, functional excipients such as crystalline cellulose are mixed or the amount of lubricant is increased. We are trying to improve the tableting property.

However, in this case, when the orally disintegrating tablet is administered, the texture is poor, a foreign body sensation is felt, and the disintegrating time becomes long.

Republic of Korea Published Patent Gazette No. 10-2005-0118775 Republic of Korea Registered Patent Gazette No. 10-1554374 Republic of Korea Published Patent Gazette No. 10-2013-0009416 Republic of Korea Registered Patent Gazette No. 10-1531030

In order to solve the above problems, the present invention obtains high hardness even with low-pressure tableting by wet-granulating sugar or sugar alcohol with an ethyl cellulose solution, surface-modifying it, and applying it to orally disintegrating tablets. It can be applied to actual production without tableting trouble, and it does not collapse during handling during drug manufacturing, transportation, storage, packaging, and preparation work, and even if it is stored for a long time under high humidity conditions. An object of the present invention is to provide an orally disintegrating tablet capable of suppressing a decrease in hardness and a delay in disintegration.

In order to achieve the above object, in the present invention,
Provided is an orally disintegrating tablet containing sugar or sugar alcohol granules which have been wet-granulated with an ethyl cellulose solution and surface-modified as a main excipient.

In the orally disintegrating tablet, the sugar is preferably one or more selected from glucose, maltose, dextrose, lactose, trehalose and white sugar.

In the orally disintegrating tablet, the sugar alcohol is preferably one or more selected from mannitol, sorbitol, xylitol, erythritol, maltitol and lactitol.

In the orally disintegrating tablet, the ethyl cellulose preferably has a viscosity of 6 to 55 cps.

In the orally disintegrating tablet, the sugar or sugar alcohol granules are preferably granulated by mixing sugar or sugar alcohol and an ethyl cellulose solution in a weight ratio of 10: 1 to 80: 1 on a solid content basis.

In the orally disintegrating tablet, the sugar or sugar alcohol modified with ethyl cellulose is preferably contained in an amount of 35 to 80% by weight based on the total weight of the orally disintegrating tablet.

In the orally disintegrating tablet, the sugar or sugar alcohol modified with ethyl cellulose is preferably contained in an amount of 60 to 80% by weight based on the total weight of the orally disintegrating tablet.

The orally disintegrating tablet may further contain a disintegrating agent.
In the orally disintegrating tablet, the disintegrating agent is preferably one or more selected from crospovidone, croscarmellose sodium, hydroxypropyl starch and sodium starch glycolate.

In the orally disintegrating tablet, the ethyl cellulose solution is preferably ethanol in which ethyl cellulose is dispersed.

In the orally disintegrating tablet, it is preferable to use a fluidized bed granulation method for the wet granulation.

In the orally disintegrating tablet, it is preferable to use hard anhydrous silicic acid as a fluidizing agent in the fluidized bed granulation method.

In the orally disintegrating tablet, the fluidizing agent is preferably used in an amount of 0.1 to 1.0% by weight based on the total weight of the solid content of the main excipient.

The main excipient in the form of granules in which the sugar or sugar alcohol of the present invention is surface-modified with an ethyl cellulose solution has excellent tableting properties because ethyl cellulose retains the skeleton of the tablet, and acts as a water channel when administered orally, and is rapid. Does not interfere with collapse. By applying such a main excipient to orally disintegrating tablets, high hardness can be obtained even with low-pressure tableting, actual production application is possible without tableting obstacles, and drug production, transportation, storage, and minute production are possible. During packaging and preparation work, it does not collapse during handling, and even if it is stored for a long period of time under high humidity conditions, it is possible to suppress a decrease in hardness and a delay in disintegration.

It is a graph which shows the result of having confirmed the hardness by the tableting pressure with respect to the sample of Example 5 and Comparative Example 6.

The orally disintegrating tablet of the present invention is characterized in that sugar or sugar alcohol granules that have been wet-granulated with an ethyl cellulose solution and surface-modified are used as the main excipient.

Sugar or sugar alcohol granules that have been surface-modified by wet granulation with an ethyl cellulose solution are produced as follows.

As the sugar, glucose, maltose, dextrose, lactose, trehalose, sucrose and the like can be used, and as the sugar alcohol, mannitol, sorbitol, xylitol, erythritol, maltitol, lactitol and the like can be used. It is more preferable to use mannitol.

An ethyl cellulose solution is used as a substance for wet granulating sugar or sugar alcohol. As the solvent of the ethyl cellulose solution, ethanol is preferably used, and 75% ethanol is particularly preferable. Ethyl cellulose solution is prepared by dispersing ethyl cellulose in ethanol.

It is preferable to use ethyl cellulose having a viscosity of 6 to 55 cps. Most preferably, one having a viscosity of 6 to 11 cps can be used. Wet granulation with ethyl cellulose having a viscosity of 6 to 11 cps results in an appropriate granule size and can shorten the disintegration time.

The sugar or sugar alcohol is wet-granulated with an ethyl cellulose solution to modify the surface of the sugar or sugar alcohol and granulate it.

At this time, the sugar or sugar alcohol and the ethyl cellulose solution are preferably mixed in a weight ratio of 10: 1 to 80: 1 based on the solid content. It is more preferable to mix in a weight ratio of 20: 1 to 30: 1.

It is preferable to use a wet granulation method as the granulation method, but when the wet granulation method is used, a uniform particle size can be obtained as compared with the case where the dry granulation method is used, and the ratio of fine particles can be obtained. This is because granules having good moldability are generally obtained.

As the wet granulation method, ordinary wet granulation methods such as a fluidized bed granulation method, a stirring granulation method, a cylindrical extrusion granulation method, a rolling fluidized bed granulation coating method, and a spray drying method can be used. , It is more preferable to use a fluidized bed granulation method using a fluidized bed granulator.

The fluidized bed granulation method is a method in which a mixture of a pharmaceutical ingredient and a pharmaceutical excipient is maintained in a fluid state, a solution or suspension containing a binder or the like is sprayed, and the mixtures are aggregated and granulated by the binder. is there.

In order to granulate the main excipient by the fluidized bed granulation method, it is more preferable to use a fluidizing agent and hard anhydrous silicic acid as the fluidizing agent. The fluidizing agent is preferably used in an amount of 0.1 to 1.0% by weight based on the total weight of the solid content of the main excipient.

In the surface-modified granular form of the main excipient, ethyl cellulose maintains the skeleton of the tablet, has excellent tableting properties, acts as a water channel when administered orally, and does not interfere with rapid disintegration.
Orally disintegrating tablets are produced using the main excipient.

Orally disintegrating tablets are produced by ordinary methods except that the main excipient is used.

The sugar or sugar alcohol modified with ethyl cellulose, which is the main excipient, is preferably contained in an amount of 35 to 80% by weight, more preferably 45 to 80% by weight, based on the total weight of the orally disintegrating tablet. , 60-80% by weight, most preferably.

The orally disintegrating tablet of the present invention contains a sugar or sugar alcohol modified with ethyl cellulose as a main excipient and contains a disintegrating agent.

As the disintegrant, crospovidone, croscarmellose sodium, hydroxypropyl starch, sodium starch glycolate and the like can be used. The disintegrating agent is preferably contained in an amount of 6 to 25% by weight, more preferably 7 to 20% by weight, and most preferably 8 to 15% by weight based on the total weight of the orally disintegrating tablet.

The orally disintegrating tablet of the present invention includes a binder, a lubricant, a sweetener, a sub-excipient, a surfactant, an acidulant, a foaming agent, a stabilizer, a flavoring agent (fragrance), a coloring agent, and a preservative. A pH regulator or the like can be further included as long as the disintegration of the tablet is not damaged.

As the binder, hydroxypropyl cellulose, alginic acid, gelatin, partially pregelatinized (pregelatinized) starch, povidone, gum arabic, pullulan, dextrin and the like can be used. It is more preferable to use partially pregelatinized starch as a binder, but partially pregelatinized starch exerts a sufficient effect as a binder, exhibits good granulation property, and maintains tablet hardness while maintaining tablet hardness. This is because it does not interfere with the disintegration of.

As the lubricant, stearic acid, magnesium stearate, calcium stearate, sucrose fatty acid ester, polyethylene glycol, sodium stearyl fumarate, colloidal silicon dioxide, talc, glyceryl behenate, magnesium aluminometasilicate, etc. can be used. it can. Of these, magnesium stearate is more preferable, but a sufficient gliding effect can be obtained by adding a small amount.

As the sweetener, sodium saccharin, dipotassium glycyrrhizinate, aspartame, stevia, thaumatin, sucralose, stevioside, neohesperidin, alitame, acesulfame potassium and the like can be used.

By-excipients may include unmodified sugars and sugar alcohols, microcrystalline cellulose, corn starch, starch hydrolysates (dextrin, maltodextrin, etc.), carboxymethyl cellulose calcium, hardened oil, talc, etc. it can.

As the surfactant, polyoxyethylene hydrogenated castor oil, polyoxyethylene polyoxypropylene glycol, sorbitan fatty acid ester, polysorbate, fatty acid glycerin ester, sodium lauryl sulfate and the like can be used.

As the acidulant, citric acid, tartaric acid, malic acid, ascorbic acid and the like can be used.

As the foaming agent, sodium hydrogen carbonate, sodium carbonate and the like can be used.

As the stabilizer, sodium edetate, tocopherol, cyclodextrin and the like can be used.

As the flavoring agent (fragrance), lemon oil, orange oil, menthol and the like can be used.

As the colorant, edible red No. 2, edible blue No. 2, edible yellow No. 5, edible lake pigment, diiron trioxide and the like can be used.

As the preservative, sodium benzoate, methyl paraoxybenzoate, propyl paraoxybenzoate and the like can be used.

As the pH adjuster, citric acid, calcium hydrogen phosphate, sodium hydrogen carbonate and the like can be used.

As the mixing method, a usual method such as mixing, kneading, and granulation is used. For example, vertical granulator VG10 [manufactured by Paulec], universal kneader (manufactured by Hata Iron Works), fluidized bed granulator LAB-1, FD-3S [manufactured by Paulec], rolling fluidized coating granulator MP It can be mixed using a device such as -10 or MP-400 [manufactured by Paulec].

As the granulation method, a wet granulation method and a dry granulation method, which are known methods, can be used. In the case of the wet granulation method, ordinary wet granulation methods such as a fluidized bed granulation method, a stirring granulation method, a cylindrical extrusion granulation method, a rolling fluidized bed granulation coating method, and a spray drying method can be used. .. In the case of the dry granulation method, granulation can be performed using a dry granulator such as a roller compactor or a normal dry granulator such as a slag locker.

The drying method is a drying method usually used for producing tablets, such as vacuum drying and fluidized bed drying.

The tableting is preferably performed using a single-shot tablet machine (manufactured by Kikusui Seisakusho), a rotary tablet press machine (manufactured by Kikusui Seisakusho), or the like, and is preferably 3.0 to 30.0 kN / cm ² , preferably 6.0. It is preferable to lock at a pressure of ~ 12.0 kN / cm ² .

Hereinafter, the present invention will be described in more detail with reference to Examples. The following examples illustrate the present invention, and the scope of the present invention is not limited thereto.

<Manufacturing example 1>
66.3 g of D-mannitol and 0.35 g of hard silicon dioxide were put into a fluidized bed granulator (Friend-Vector VFC-LAB Micro), and 3.33 g of ethyl cellulose (7 cps) was dispersed in 111.0 g of 75% ethanol. Granules were produced by granulating with a solution and then drying.

<Manufacturing example 2>
66.3 g of D-mannitol and 0.35 g of hard silicon dioxide were put into a fluidized bed granulator (Friend-Vector VFC-LAB Micro), and 3.33 g of ethyl cellulose (10 cps) was dispersed in 111.0 g of 75% ethanol. Granules were produced by granulating with a solution and then drying.

<Manufacturing example 3>
66.3 g of D-mannitol and 0.35 g of hard silicon dioxide were put into a fluidized bed granulator (Friend-Vector VFC-LAB Micro), and 3.33 g of ethyl cellulose (50 cps) was dispersed in 111.0 g of 75% ethanol. Granules were produced by granulating with a solution and then drying.

<Manufacturing example 4>
67.4 g of D-mannitol and 0.35 g of hard silicon dioxide were put into a fluidized bed granulator (Friend-Vector VFC-LAB Micro), and 2.26 g of ethyl cellulose (7 cps) was dispersed in 75.4 g of 75% ethanol. Granules were produced by granulating with a solution and then drying.

<Example 1>
56.0 g of D-mannitol modified with ethyl cellulose (7 cps), 7.0 g of corn starch, and 1.8 g of magnesium aluminometasilicate of Production Example 1 were put into a fluidized bed granulator, mixed, and mixed with PC-10. Granules were produced by granulating 2.1 g with a dispersion liquid dispersed in 70.0 g of purified water and then drying.

To 66.8 g of the obtained granules, 1.9 g of crospovidone CL-SF, 0.7 g of aspartame, and 0.6 g of magnesium stearate were added and mixed in a polyethylene plastic bag to prepare a tableting mixture.

The tableting mixture was tableted at a tableting pressure of 6 to 7 kN to obtain a tablet having a diameter of 7.2 mm and a weight of 150 mg.

<Example 2>
47.9 g of D-mannitol modified with ethyl cellulose (7 cps) of Production Example 1, 7.0 g of corn starch, and 1.8 g of magnesium aluminometasilicate were put into a fluidized bed granulator and mixed, and PC-10 was added. Granules were produced by granulating 2.1 g with a dispersion liquid dispersed in 70.0 g of purified water and then drying.

To 58.8 g of the obtained granules, 7.0 g of D-mannitol modified in Production Example 4, 3.3 g of crospovidone CL-SF, 0.7 g of aspartame, and 0.6 g of magnesium stearate were added to a polyethylene plastic bag. To produce a tableting mixture.

The tableting mixture was tableted at a tableting pressure of 6 to 7 kN to obtain a tablet having a diameter of 7.2 mm and a weight of 150 mg.

<Example 3>
56 g of D-mannitol modified with ethyl cellulose (10 cps) of Production Example 2 above, 7.0 g of corn starch, and 1.8 g of magnesium aluminometasilicate were put into a fluidized bed granulator and mixed, and PC-10 2. Granules were produced by granulating 1 g with a dispersion liquid dispersed in 70.0 g of purified water and then drying.

To 66.8 g of the obtained granules, 1.9 g of crospovidone CL-SF, 0.7 g of aspartame, and 0.6 g of magnesium stearate were added and mixed in a polyethylene plastic bag to prepare a tableting mixture.

The tableting mixture was tableted at a tableting pressure of 6 to 7 kN to obtain a tablet having a diameter of 7.2 mm and a weight of 150 mg.

<Example 4>
56 g of D-mannitol modified with ethyl cellulose (50 cps) of Production Example 3 above, 7.0 g of corn starch, and 1.8 g of magnesium aluminometasilicate were put into a fluidized bed granulator and mixed, and PC-10 2. Granules were produced by granulating 1 g with a dispersion liquid dispersed in 70.0 g of purified water and then drying.

To 66.8 g of the obtained granules, 1.9 g of crospovidone CL-SF, 0.7 g of aspartame, and 0.6 g of magnesium stearate were added and mixed in a polyethylene plastic bag to prepare a tableting mixture.

The tableting mixture was tableted at a tableting pressure of 6 to 7 kN to obtain a tablet having a diameter of 7.2 mm and a weight of 150 mg.

<Example 5>
33.4 g of D-mannitol modified with ethyl cellulose (7 cps), 4.0 g of corn starch, and 1.0 g of magnesium aluminometasilicate of Production Example 1 were put into a fluidized bed granulator and mixed, and PC-10 was added. Granules were produced by granulating 1.2 g with a dispersion liquid dispersed in 40.0 g of purified water and then drying.

36.9 g of diphenhydramine drug pellets were added to 39.5 g of the obtained granules and mixed in a polyethylene plastic bag, and then 2.1 g of crospovidone CL-SF, 0.9 g of aspartame and 0.6 g of magnesium stearate were added to the polyethylene vinyl. Mixing in bags produced a tableting mixture.

The tableting mixture was tableted at tableting pressures of 11 to 12 kN, 15 to 16 kN, and 22 kN, respectively, to obtain tablets having a diameter of 9.0 mm and a weight of 229.2 mg.

<Comparative example 1>
54.6 g of unmodified general D-mannitol, 7.0 g of corn starch, and 1.8 g of magnesium aluminometasilicate were put into a fluidized bed granulator and mixed, and 2.1 g of PC-10 was added to purified water 70. Granules were produced by granulating with a dispersion liquid dispersed in 0.0 g and then drying.

To 65.4 g of the obtained granules, 3.3 g of crospovidone CL-SF, 0.7 g of aspartame, and 0.6 g of magnesium stearate were added and mixed in a polyethylene plastic bag to prepare a tableting mixture.

The tableting mixture was tableted at a tableting pressure of 11 to 12 kN to obtain a tablet having a diameter of 7.2 mm and a weight of 150 mg.

<Comparative example 2>
54.6 g of unmodified general D-mannitol, 7.0 g of corn starch, and 1.8 g of magnesium aluminometasilicate were put into a fluidized bed granulator and mixed, and 2.1 g of PC-10 was added to purified water 70. Granules were produced by granulating with a dispersion liquid dispersed in 0.0 g and then drying.

To 65.4 g of the obtained granules, 1.9 g of crospovidone CL-SF, 1.4 g of ethyl cellulose (7 cps) powder, 0.7 g of aspartame, and 0.6 g of magnesium stearate were added and mixed in a polyethylene plastic bag to prepare a tableting mixture. Manufactured.

The tableting mixture was tableted at a tableting pressure of 11 to 12 kN to obtain a tablet having a diameter of 7.2 mm and a weight of 150 mg.

<Comparative example 3>
54.6 g of unmodified general D-mannitol, 1.4 g of ethyl cellulose (7 cps) powder, 7.0 g of corn starch, and 1.8 g of magnesium aluminometasilicate were put into a fluidized bed granulator and mixed, and PC was added. -10 2.1 g was granulated with a dispersion liquid dispersed in 70.0 g of purified water and then dried to produce granules.

To 66.8 g of the obtained granules, 1.9 g of crospovidone CL-SF, 0.7 g of aspartame, and 0.6 g of magnesium stearate were added and mixed in a polyethylene plastic bag to prepare a tableting mixture.

The tableting mixture was tableted at a tableting pressure of 11 to 12 kN to obtain a tablet having a diameter of 7.2 mm and a weight of 150 mg.

<Comparative example 4>
54.6 g of unmodified general D-mannitol, 1.4 g of ethyl cellulose (10 cps) powder, 7.0 g of corn starch, and 1.8 g of magnesium aluminometasilicate were put into a fluidized bed granulator and mixed, and PC was added. -10 2.1 g was granulated with a dispersion liquid dispersed in 70.0 g of purified water and then dried to produce granules.

To 66.8 g of the obtained granules, 1.9 g of crospovidone CL-SF, 0.7 g of aspartame, and 0.6 g of magnesium stearate were added and mixed in a polyethylene plastic bag to prepare a tableting mixture.

The tableting mixture was tableted at a tableting pressure of 11 to 12 kN to obtain a tablet having a diameter of 7.2 mm and a weight of 150 mg.

<Comparative example 5>
54.6 g of unmodified general D-mannitol, 1.4 g of ethyl cellulose (50 cps) powder, 7.0 g of corn starch, and 1.8 g of magnesium aluminometasilicate were put into a fluidized bed granulator and mixed, and PC was added. -10 2.1 g was granulated with a dispersion liquid dispersed in 70.0 g of purified water and then dried to produce granules.

To 66.8 g of the obtained granules, 1.9 g of crospovidone CL-SF, 0.7 g of aspartame, and 0.6 g of magnesium stearate were added and mixed in a polyethylene plastic bag to prepare a tableting mixture.

The tableting mixture was tableted at a tableting pressure of 11 to 12 kN to obtain a tablet having a diameter of 7.2 mm and a weight of 150 mg.

<Comparative Example 6>
32.3 g of unmodified general D-mannitol, 1.1 g of ethyl cellulose (7 cps) powder, 4.0 g of corn starch, and 1.0 g of magnesium aluminometasilicate were put into a fluidized bed granulator, mixed, and mixed. -10 1.2 g was granulated with a dispersion liquid dispersed in 40.0 g of purified water and then dried to produce granules.

After mixing 36.9 g of diphenhydramine drug pellets with 39.5 g of the obtained granules in a polyethylene plastic bag, 2.1 g of crospovidone CL-SF, 0.9 g of aspartame and 0.6 g of magnesium stearate are added in a polyethylene plastic bag. It was mixed to produce a tableting mixture.

The tableting mixture was tableted at tableting pressures of 21 to 22 kN, 27 kN, and 40 to 42 kN, respectively, to obtain tablets having a diameter of 9.0 mm and a weight of 229.2 mg.

[Experimental example]
Evaluation Method The hardness (kp), decay time (sec), and degree of abrasion were evaluated for the samples of Examples and Comparative Examples by the following methods.

1. Hardness The hardness of tablets was measured using a hardness measuring machine (PTB 311E manufactured by Pharma Test) and expressed as an average value measured 5 times.

2. Disintegration time The disintegration time of tablets was measured using a disintegration measuring device (Tricorptester of OKADA SEIKO CO., LTD.) And expressed as an average value measured 5 times.

3. Abrasion degree The abrasion degree of tablets was confirmed by the test method described in the 11th revision of the Korean Pharmaceutical Code. That is, first, the tablet weight before and after the test was measured, and the reduction rate of the tablet weight was calculated by the following mathematical formula 1.

4. Humidity-free packaging stability test A saturated salt solution for 75% humidity conditions is produced using deionized water or purified water, and the solution is saturated when about 5% of chloride becomes insoluble in the solution. It was considered to be in a state of being. When the humidity was stabilized by putting this saturated salt solution in a desiccator, the hardness and disintegration time with the passage of time were measured while storing the sample in a Petri dish, and the average value measured 5 times was shown.

5. Sensory Test Three to five subjects placed tablets on the oral tongue and allowed them to disintegrate spontaneously. Subsequent tablets are included in the oral cavity and the feeling of administration when they are completely disintegrated is judged to be in three stages (○: good, △: normal, ×: poor), and for the judgment of ×, the detailed feeling of administration is shown in parentheses. Described inside.

<Experimental example 1>
Confirmation of hardness, degree of abrasion, disintegration time and presence or absence of locking disorder The hardness, degree of abrasion, disintegration time and presence or absence of locking disorder of the samples of Examples 1 to 4 and Comparative Examples 1 to 5 were confirmed, and the results are shown below. It is shown in Table 1 of.

From the results in Table 1 above, it can be seen that the samples of the examples are generally excellent in hardness, degree of abrasion, disintegration time and presence / absence of locking failure.

<Experimental example 2>
Humidity-free packaging stability test method The humidity-free packaging stability of the tablets produced in Examples 1 and 2 and Comparative Examples 1 and 2 was tested as follows.

A saturated salt solution for 75% humidity conditions was produced using deionized water or purified water, and when about 5% of chloride became insoluble in the solution, the solution was considered to be saturated. ..

When the humidity is stabilized by putting this saturated salt solution in a desiccator, the hardness and decay time with the passage of time are measured while storing the sample in a Petri dish, and the average value measured 5 times is shown in Table 2 below. Each is shown in Table 3.

From the results in Tables 2 and 3 above, it can be seen that the sample of Example is superior in stability to the sample of Comparative Example over time.

<Experimental example 3>
Confirmation of hardness, degree of abrasion and decay time The hardness, degree of abrasion and decay time were confirmed for the samples of Example 5 and Comparative Example 6, and the results are shown in Table 4 below.

As can be confirmed from the results in Table 4 above, the samples of Example 5 and Comparative Example 6 showed a decay time 10 seconds earlier than that of the sample of Example 5 at the same hardness.

<Experimental Example 4>
Confirmation of tableting property The hardness of the samples of Example 5 and Comparative Example 6 was confirmed by the tableting pressure. The results are shown in Table 5 and FIG. 1 below.

As can be confirmed from the results of Table 5 and FIG. 1 above, the tablet of Example 5 exhibited higher hardness with a lower tableting pressure than the tablet of Comparative Example 6. This indicates that since the main excipient whose surface is modified is used, the tableting property is superior to that when the main excipient which is not modified is used.

<Experimental Example 5>
Sensory test

In Example 5, the disintegration was rapid and the feeling of administration was good, and in Comparative Example 6, the pellet coating was torn thinly due to the large amount of tableting pressure, and the bitterness of the drug was felt, and the feeling of residue and roughness was felt. Received an evaluation that it can be felt.

Claims (2)

The main excipient was surface-modified by wet granulation using an ethyl cellulose solution.
The ethyl cellulose solution is obtained by dispersing ethyl cellulose having a viscosity of 6 to 55 cps in a solvent.
The main excipient is composed of mannitol and hard silicic anhydride .
The main excipient and the ethyl cellulose solution are used in a weight ratio of 20: 1 to 30: 1 based on the solid content.
At the stage of producing surface-modified main excipients;
Disintegrants, binders, lubricants, sweeteners, sub-excipients, surfactants, acidulants, foaming agents, stabilizers, and deposits on the surface-modified main excipients produced in the above steps. At the stage of manufacturing granules, which is obtained by mixing one or more selected from fragrances (fragrances), colorants, preservatives, and pH adjusters, and granulating them.
A step of tableting a tableting mixture containing the granules and a drug produced in the above step to prepare a tablet containing 35 to 80% by weight of the surface-modified main excipient in the tablet;
A method for producing an orally disintegrating tablet. The method for producing an orally disintegrating tablet according to claim 1 , wherein the disintegrating agent is at least one selected from crospovidone, croscarmellose sodium, hydroxypropyl starch and sodium starch glycolate. ..