JP2007197373A - Method for producing intraorally quickly disintegrating tablet - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for producing an intraorally quickly disintegrating tablet having excellent disintegrability, sufficient hardness and abrasion resistance in an ordinary handling and good administration feeling by conventionally known ordinary production equipment without requiring specifically new production equipment. <P>SOLUTION: A particle containing 5-40 wt.% of a crystallized saccharide or a granulated saccharide is used as a nucleus, a solution containing a water-soluble polymer and/or a water-insoluble polymer is added to the particle, the particle is subjected to powder coating with a medicine or medicine-containing powder. The particle is mixed with 1-30 wt.% of a disintegrator and 0.1-5 wt.% of a lubricant and tableted under 100-900kgf tableting pressure to give the intraorally quickly disintegrating tablet. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a method for producing an orally rapidly disintegrating tablet that is rapidly disintegrated or dissolved in the oral cavity having excellent usability and has a good feeling of use, using conventional production equipment as it is. Contains particles coated with a drug or a powder containing a drug using a solution or dispersion containing a water-soluble polymer and / or a water-insoluble polymer as a core, and consisting of saccharide particles. The present invention relates to a method for producing an intraoral rapidly disintegrating tablet.

  Orally disintegrating preparations are described in “Silver Science Research, Ministry of Health and Welfare Science” by Sugihara et al. P. The introduction of Scherer's ZYDIS formulation was the beginning, and research and development became active. “Immediately useful particle design and processing technology (Jiho) 221 pages, 2003”.

  In recent years, active research has been conducted on tablets that dissolve or disintegrate rapidly in the oral cavity as dosage forms that can be easily taken by patients such as the elderly and children who are difficult to take ordinary oral preparations. There are also many commercialized products “Pharm.Tech.Japan, Vol. 14, No. 11, p. 111, 1998”.

As is well known, methods for producing orally disintegrating tablets are roughly divided into three. The first is a template formulation. This is a method in which a drug suspension in which a drug is dispersed or dissolved is filled in a pocket such as a pre-formed PTP seal and sealed after lyophilization. The second is a wet tablet, a wet powder containing the drug. It is a method in which a body is molded at a very low pressure and dried to form a strong tablet. The third method is a general tablet type formulation. This is divided into a porous molded body preparation, a preparation using an easily moldable additive, and a disintegration mechanism devised preparation. The tablet strength is improved by heat treatment or the like.
The preparation using an easily moldable additive is intended to improve moldability by miniaturization of an easily moldable additive such as crystalline cellulose and an additive such as sugar.
In addition, the disintegration mechanism devised formulation is intended to improve disintegration by using a super disintegrant, reducing the amount of lubricant (external lubricant), and using foaming action by acid-base reaction. Technology (Jiho), p.221, 2003 and Pharm.Tech.Japan, Vol. 14, No. 11, p.111, 1998 ”.

  Patent Document 1 discloses an intraoral rapidly disintegrating tablet that is filled with a suspension in a resin film sheet for PTP packaging and dried under reduced pressure, and then used as a tablet. A special manufacturing apparatus is required instead of an apparatus, and the hardness of the tablet is about 1 to 2 kg, the tablet is easily broken, and handling is difficult during manufacturing, distribution and administration.

  Patent Document 2 discloses that after tableting, the tablet is converted into a tablet through a humidification chamber and a drying chamber by a belt conveyor, and this manufacturing method is also special as in Patent Document 1. Manufacturing equipment is required.

  Patent Document 3 discloses a tablet manufacturing method including forming a wet powder into a tablet shape by a molding die through an anti-sticking film. In this manufacturing method, Patent Document 1 and Special manufacturing equipment is required as well as two.

  As described above, in any of Patent Documents 1 to 3, a special manufacturing facility is required for the manufacture, instead of a conventional facility existing in the past.

  As an intraoral quick-disintegrating tablet produced by conventional production equipment existing from the past, Patent Document 4 includes an intraoral quick-disintegrating tablet obtained by compressing granules and crystalline cellulose consisting of a saccharide and a swellable excipient, It is disclosed that crystalline cellulose is important for ensuring tablet strength.

  However, in Patent Document 4, even if the hardness of the tablet is maintained to some extent, it is important to ensure the friability of the tablet in order to prevent the manufacturing process, the distribution stage, and breakage during taking. There is no mention or suggestion of any points.

Patent Document 5 discloses a method for producing an orally disintegrating tablet containing an inorganic excipient that is insoluble in water, but the orally disintegrating tablet obtained by this method is unnecessary for water. Since it contains an inorganic excipient, there is a problem in terms of taking feeling such as roughness in the oral cavity.
Japanese Patent No. 2807346 Japanese Patent Laid-Open No. 2000-09574 JP 2002-087958 A JP 2000-016930 A Japanese Patent Laid-Open No. 2004-051609

  The problem to be solved by the present invention is that an intraoral quick-disintegrating tablet having excellent utility can be produced only by special production equipment, not by conventional production equipment.

  Therefore, the object of the present invention is to provide excellent disintegration, sufficient hardness and wear resistance in ordinary handling by a conventional production facility that has been conventionally known, without requiring special new production facilities, and An object of the present invention is to provide a method capable of producing an intraoral rapidly disintegrating tablet having a good feeling of administration.

  As a result of intensive studies to achieve the above-mentioned object, the present inventors have made saccharide particles (lactose, xylitol crystals, etc.) as cores, water-soluble polymers (polyvinylpyrrolidone, etc.) and / or water. Using a solution or dispersion containing an insoluble polymer (such as ethyl cellulose), particles coated with a drug or powder containing a drug, a disintegrant (such as crospovidone), and an excipient (crystalline cellulose, sugar alcohol, Sugar, anhydrous silicic acid, etc.) and mixing with the internal lubrication method or external lubrication method (lubricant magnesium stearate, etc.) to find that the desired intraoral rapidly disintegrating tablet can be produced. Completed the invention.

  That is, the method for producing an intraoral rapidly disintegrating tablet according to claim 1 of the present invention uses a crystallized saccharide or a granulated saccharide particle as a core, and is insoluble in a water-soluble polymer and / or water. A solution containing a polymer is added, powder coated with a drug or powder containing a drug, a disintegrant and a lubricant are added to the powder coated particles, and tableting is performed.

  The method for producing an intraoral rapidly disintegrating tablet according to claim 2, wherein the content of the crystallized saccharide or granulated saccharide is 5 to 40% by weight based on the total weight of the tablet, The content is 1 to 30% by weight, and the content of the lubricant is 0.1 to 5% by weight.

  The method for producing an intraoral rapidly disintegrating tablet according to claim 3 is characterized in that the tableting pressure in the case of tableting is 100 to 900 Kgf.

  According to the present invention, without requiring a special new production facility, using a conventional conventional pharmaceutical production facility as it is, with excellent disintegration and sufficient hardness and wear resistance in normal handling, In addition, it is possible to produce an intraoral quick disintegrating tablet with a good feeling of taking.

  The method for producing an intraoral rapidly disintegrating tablet according to the present invention comprises a saccharide crystallized in a tablet or a particle containing 5 to 40% by weight of granulated saccharide as a core, and a water-soluble polymer and / or water. Particles coated with a drug or a powder containing a drug using a solution containing an insoluble polymer, 1 to 30% by weight of crospovidone, carboxymethylcellulose, partially pregelatinized starch, low-substituted hydroxypropylcellulose Corn starch disintegrant and 0.1-5% by weight of magnesium stearate, calcium stearate, stearic acid, stearyl alcohol, sucrose fatty acid ester and talc lubricant and mixed with tableting pressure of 100-900 Kgf Tablets are made into tablets by the internal lubrication method or the external lubrication method.

  In addition, this invention is applicable also to fields, such as a quasi-drug and a foodstuff, including the pharmaceutical field | area.

  The particles (core) made of saccharides used in the present invention are sugars such as lactose, fructose and glucose, sugar alcohols such as maltitol, xylitol and mannitol, respective crystals, or powders of sugar and sugar alcohol. And the like.

  Examples of the water-soluble polymer used in the present invention include polyvinylpyrrolidone, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinyl alcohol, polyethylene glycol, gum arabic, sodium alginate, gelatin, pullulan and the like. These water-soluble polymers may be used alone or in combination of two or more.

  Moreover, you may mix | blend a fragrance | flavor, a stabilizer, etc. as needed.

  The content of particles (core) composed of saccharides used in the present invention is 5 to 40% by weight with respect to the total amount of the tablet, but when the content of crystalline lactose is 0% by weight, the disintegration degree of the tablet (same hardness) is low. Compared with the disintegration degree of tablets containing crystalline lactose, there is a tendency to be delayed, and the flowability of the powder for tableting is also inferior. When the crystalline lactose content is 30% by weight or more, the tablet hardness is 3 kp. It is difficult to ensure, and further 40% by weight tends to increase the degree of wear, so the content of saccharide particles (core) is preferably 5 to 20% by weight.

  Further, the content of the disintegrant in the present invention is 1 to 30% by weight, but when the blending amount of crospovidone as a disintegrant is 0% by weight, the disintegration degree of the tablet (same hardness) is blended with crospovidone. Compared with the disintegration degree of the tablet, there is a tendency to be delayed, and when the content of crospovidone is 10% by weight or more, the fluidity of the tableting powder tends to be deteriorated, and when it is 30% by weight, wear is observed. Since the tendency to increase is also observed, the content of the disintegrant is preferably 1 to 10% by weight.

  Further, the content of the lubricant used in the present invention is 0.1 to 5% by weight. When the blending amount of magnesium stearate as the lubricant is 0% by weight, the tableting to the tablet press is performed. Adhesion of the powder for use was observed, and at 2.0% by weight, a tendency to delay disintegration was observed. Therefore, the content of the lubricant is preferably 0.1 to 2% by weight.

  The tableting pressure in the present invention is 100 to 900 Kgf, but the tablets were tableted at a tableting pressure of 100, 200, 300, 400 and 500 Kgf, and the physical properties were measured. In order to further improve the degree of wear, the tablet is preferably 200 kgf or more, and to satisfy the disintegration, tablet hardness, and wear degree, the tablet should be tableted with a tableting pressure of 200 to 800 kgf. Is preferred.

  The method of adding a lubricant in the present invention may be an internal lubrication method in which a conventional tableting powder is mixed and mixed, but it is preferable that the lubricant is slipped on a punch or a die mounted on a tableting machine. This is an external lubrication method in which a powder is applied.

  Various ingredients can be blended in the tablet of the present invention depending on the application. In the pharmaceutical field, for example, antihistamines such as chlorpheniramine maleate, diphenhydramine hydrochloride, and promethazine as pharmaceutical ingredients. Antitussive expectorants such as dextromethorphan hydrobromide, guaifenesin, and theophylline. Antihypertensive agents such as captolyl, methyldopa, and labetalol hydrochloride. Arrhythmic agents such as pindolol, propranolol hydrochloride, procainamide hydrochloride. Diuretics such as isosorbide and furosemide. Antispasmodic drugs such as scopolamine hydrobromide and papaverine hydrochloride. Healthy stomach digesters such as funnel extract, diastase, and cinnamon oil. Intestinal agents such as berberine chloride, lactic acid bacteria, bifidobacteria. Antacids such as magnesium oxide, magnesium carbonate, sucralfate. Anti-ulcer agents such as cimetidine, ranitidine, famotidine. Antipyretic analgesics and anti-inflammatory drugs such as acetaminophen, ibuprofen, etenzamide. Hypnotic sedatives such as diazepam, nitrazepam, and phenobarbital sodium. Antidepressants such as amphetamine and imipramine.

  Nutritional tonic health medicines are naturally derived substances such as herbal medicines and herbal medicines. Minerals such as protein, amino acid, iron, calcium, magnesium. Vitamins such as vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, and vitamin E are included.

  EXAMPLES The present invention will be described in detail below with reference to examples, but these do not limit the present invention.

Example 1
Crystal lactose (50M) 10g is put into a mixer, and PVPK-30 (solid component 0.045g) ethanol solution is added here. Ascorbic acid is added in 5 to 6 portions (add about 2 g at a time and repeat this operation). After powder coating, it is dried and sized to form coated particles. Granulated lactose (Asahi Kasei Co., Ltd., trade name: Super Tab) 16.5 g, crystalline cellulose (Asahi Kasei Co., Ltd. trade name: Avicel PH102), crospovidone (BASF Takeda Vitamin Co., Ltd.) : Kollidon CL) 3 g and maltitol (Towa Kasei Kogyo Co., Ltd. trade name: powdered maltitol G3) 22 g are added and mixed. To this mixture, 0.3 g of magnesium stearate was added and mixed, and a tableting machine was used to obtain an intraoral rapidly disintegrating tablet having a tablet weight of 200 mg at a tableting pressure of 200 kgf.

Example 2
Using the raw material components shown in Example 1 of Table 1 and changing the tableting pressure of the tableting machine to 300 Kgf, the same operation as in Example 1 was performed to obtain an intraoral rapidly disintegrating tablet having a tablet weight of 200 mg.

Example 3
Using the raw material components shown in Example 1 of Table 1 and changing the tableting pressure of the tableting machine to 400 Kgf, the same operation as in Example 1 was performed to obtain an intraoral rapidly disintegrating tablet having a tablet weight of 200 mg.

Example 4
Using the raw material components shown in Example 1 of Table 1 and changing the tableting pressure of the tableting machine to 500 Kgf, the same operation as in Example 1 was performed to obtain an intraoral rapidly disintegrating tablet having a tablet weight of 200 mg.

Example 5
Using the raw material components shown in Example 1 of Table 1 and changing the tableting pressure of the tableting machine to 600 Kgf, the same operation as in Example 1 was performed to obtain an intraoral rapidly disintegrating tablet having a tablet weight of 200 mg.

Comparative Example 1
Ascorbic acid 10 g, lactose (200M) 26.5 g, crystalline cellulose 38.5 g, crospovidone 3 g and maltitol 22 g are charged into a mixer and mixed to obtain a uniform mixed powder. A PVPK-30 (solid content: 0.045 g) ethanol solution is added to the mixed powder, kneaded, granulated, dried, and sized. To this granulated product, 0.3 g of magnesium stearate as a lubricant was added and mixed, and a tableting machine was used to obtain an intraoral rapidly disintegrating tablet having a tablet weight of 200 mg at a tableting pressure of 200 kgf.

Comparative Example 2
Using the raw material components shown in Comparative Example 1 of Table 1, the same operation as in Comparative Example 1 was performed except that the tableting pressure of the tableting machine was changed to 300 Kgf, to obtain an intraoral rapidly disintegrating tablet having a tablet weight of 200 mg.

Comparative Example 3
Using the raw material components shown in Comparative Example 1 in Table 1, the same operation as in Comparative Example 1 was performed except that the tableting pressure of the tableting machine was changed to 400 Kgf, to obtain an intraoral rapidly disintegrating tablet having a tablet weight of 200 mg.

Comparative Example 4
Using the raw material components shown in Comparative Example 1 of Table 1 and changing the tableting pressure of the tableting machine to 500 Kgf, the same operation as in Comparative Example 1 was performed to obtain an intraoral rapidly disintegrating tablet having a tablet weight of 200 mg.

Comparative Example 5
Using the raw material components shown in Comparative Example 1 of Table 1, the same operation as in Comparative Example 1 was performed except that the tableting pressure of the tableting machine was changed to 600 Kgf to obtain an intraoral rapidly disintegrating tablet having a tablet weight of 200 mg.

Study example 1
Ascorbic acid 10 g is uniformly mixed with 10 g of lactose (200 M) and triturated. Lactose (200M) 6.5g, crystalline cellulose 38.5g, crospovidone 3g and maltitol 22g are added here and mixed uniformly. In this mixed powder, 10 g of crystal lactose is blended and mixed so as not to break the crystals. A PVPK-30 (solid content: 0.045 g) ethanol solution is added thereto and kneaded. This is granulated, dried and then sized. To this granulated powder, 0.3 g of magnesium stearate was added and mixed, and a tableting machine was used to obtain an intraoral rapidly disintegrating tablet having a tablet weight of 200 mg at a tableting pressure of 200 kgf.

Study example 2
Using the raw material components shown in Study Example 1 in Table 1, except that the tableting pressure of the tableting machine was changed to 300 Kgf, the same operation as in Study Example 1 was performed to obtain an intraoral rapidly disintegrating tablet having a tablet weight of 200 mg.

Study example 3
Using the raw material components shown in Study Example 1 in Table 1, except that the tableting pressure of the tableting machine was set to 400 Kgf, the same operation as in Study Example 1 was performed to obtain an intraoral rapidly disintegrating tablet having a tablet weight of 200 mg.

Study example 4
Using the raw material components shown in Study Example 1 in Table 1, the same operation as in Study Example 1 was performed except that the tableting pressure of the tableting machine was changed to 500 Kgf to obtain an intraoral rapidly disintegrating tablet having a tablet weight of 200 mg.

Study example 5
Using the raw material components shown in Study Example 1 in Table 1, except that the tableting pressure of the tableting machine was 600 kgf, the same operation as in Study Example 1 was performed to obtain an intraoral rapidly disintegrating tablet having a tablet weight of 200 mg.

Study example 6
Using the raw material components shown in Example 1 of Table 1, magnesium stearate was applied to the punches and mortars of the tableting machine in advance with gauze to which magnesium stearate as a lubricant was adhered, and the tableting pressure was 200 kgf Except for the above, the same operation as in Example 1 was performed to obtain an intraoral rapidly disintegrating tablet having a tablet weight of 200 mg.

Study example 7
Study Example 1 except that magnesium stearate was applied to the punches and mortars of a tableting machine with gauze to which magnesium stearate was adhered using the raw material components shown in Study Example 1 in Table 1, and the tableting pressure was set to 300 kgf. The same operation as in the above was carried out to obtain an orally rapidly disintegrating tablet having a tablet weight of 200 mg.

Study Example 8
Study Example 1 except that magnesium stearate was applied to the punches and mortars of the tableting machine with gauze to which magnesium stearate was adhered, using the raw material components shown in Study Example 1 of Table 1, and the tableting pressure was 400 kgf The same operation as in the above was carried out to obtain an orally rapidly disintegrating tablet having a tablet weight of 200 mg.

Study Example 9
Study Example 1 except that magnesium stearate was applied to the punches and mortars of a tableting machine with gauze with magnesium stearate attached using the raw material components shown in Study Example 1 in Table 1, and the tableting pressure was 500 kgf The same operation as in the above was carried out to obtain an orally rapidly disintegrating tablet having a tablet weight of 200 mg.

Study example 10
Study Example 1 except that magnesium stearate was applied to the punches and mortars of the tableting machine with gauze to which magnesium stearate was adhered, using the raw material components shown in Study Example 1 in Table 1, and the tableting pressure was 600 kgf. The same operation as in the above was carried out to obtain an orally rapidly disintegrating tablet having a tablet weight of 200 mg.

  In the said Examples 1-5, Comparative Examples 1-5, and Examination Examples 1-5, the addition method of magnesium stearate which is a lubricant is an internal lubrication method, and in Examination Examples 6-10, it is an external lubrication. Is the law.

Test example 1
Tablets obtained in Examples 1 to 5 by the powder coating method using the above crystalline lactose, Comparative Examples 1 to 5 by a conventional method using lactose without powder coating (200 M), and a conventional method using crystalline lactose The tablets obtained in Examination Examples 1 to 5 and the tablets of Examination Examples 6 to 10 obtained by the external lubrication method were tested for disintegration, hardness and friability.

  The disintegration degree of the tablets was measured using water as a test solution according to the disintegration test method described in the Japanese Pharmacopoeia, and the average value of 6 tablets was calculated. Oral disintegration time was calculated by calculating the average of three test results for each tablet for three healthy subjects.

  For the tablet hardness, an average value of 10 tablets was calculated using a tablet hardness tester (TBH200, manufactured by Elebecca). The tablet friability was measured by using a tablet friability tester (Toyama Sangyo Co., Ltd., TFT-120) described in Japanese Pharmacopoeia, rotating for 4 minutes at 25 rpm for 1 minute. The results are shown in Table 2.

  From the results in Table 2, the intraoral quick disintegrating tablets of Examples 3 and 4 had an abrasion degree of 0.5% or less, a hardness of 3 kp or more, and a disintegration degree of within 10 seconds.

  On the other hand, in the tablets of Comparative Examples 3 and 4, the hardness is 3 to 5 kp, the disintegration degree is 12 to 18 seconds, and the disintegration time is extended to about twice that of Examples 3 and 4. Further, at a tablet hardness of 7 kp, in Example 5, the disintegration time was 13 seconds, in Comparative Example 5, approximately 3 times as 33 seconds, and with the increase in tableting pressure, a significant delay was further observed in the disintegration time. . Moreover, the oral disintegration time takes about three times as long as that of the example in the comparative example.

  Therefore, the powder coating method using crystalline lactose is an excellent method for producing an intraoral rapidly disintegrating tablet. On the other hand, when powdered lactose is formulated as an excipient without using crystalline lactose, it is difficult to produce an excellent intraoral rapidly disintegrating tablet with respect to tablet strength and tablet disintegration.

  In Examples 1 to 4, the hardness is 1 to 5 kp and the degree of disintegration is within 10 seconds. On the other hand, in the comparative example 3 and the examination example 3, the hardness is 3 kp and the disintegration degree is 10 seconds or more.

  Further, in both the comparative example and the study example, as the hardness increases, the delay of the disintegration time is larger than that in the example, and at the hardness of 7 kp in the comparative example 5, the degree of disintegration is approximately three times that in the example 5. In No. 5, there was a significant delay in the decay time, more than 4 times.

  In addition, as for the disintegration time in the oral cavity, similar to the results of the disintegration degree of JP, a significant delay was observed in the disintegration time, 2 to 3 times the disintegration time of the example in the study example and 3 times in the comparative example. .

  Based on the above results, the tablets obtained in the examples in which crystalline lactose was powder-coated with ascorbic acid were tablets of comparative examples produced by conventional methods using powdered lactose in both disintegration time and disintegration time in the oral cavity. And it was shortened from the tablet of the examination example manufactured by the conventional method using crystal lactose.

  Therefore, the powder coating method using crystalline lactose is an excellent method for producing an intraoral rapidly disintegrating tablet.

Test example 2
The disintegration time of the tablet by the addition method of the lubricant was investigated. In Examples 1 to 5, as described above, a lubricant (magnesium stearate) was added and mixed in advance to obtain tablets (internal lubrication method). Examination Examples 6 to 10 were gauze in which a lubricant was previously attached as described above, and the lubricant was applied to the pestle and mortar to form tablets (external lubrication method). The results are shown in Table 3.

From the result of Table 3, compared with the internal lubrication method of Examples 1-4, in the external lubrication method of examination examples 6-9, the degree of collapse is shortened to about 1/2 at a hardness of 1-5 kp. In order to shorten the disintegration time with a hardness of 3 kp or more and a friability of 0.5% or less, the external lubrication method is excellent as a method of adding a lubricant (magnesium stearate).

The content of particles (cores) composed of saccharides used in the present invention is 5 to 40% by weight with respect to the total amount of the tablet. Compared with the disintegration degree of tablets containing crystalline lactose, there is a tendency to be delayed, and the flowability of the powder for tableting is also inferior. When the crystalline lactose content is 30% by weight or more, the tablet hardness is 3 kp. securing is difficult, because the further the milling loss of 40% by weight tended to increase, the particles (nuclei) content consisting of sugars, preferably 5 to 20 wt%.

Further, the content of the disintegrant in the present invention is 1 to 30% by weight, but when the blending amount of crospovidone as a disintegrant is 0% by weight, the disintegration degree of the tablet (same hardness) is blended with crospovidone. Compared with the disintegration degree of the tablet, there is a tendency to be delayed, and when the content of crospovidone is 10% by weight or more, the fluidity of the tableting powder tends to be deteriorated, and when the content is 30% by weight, there is a tendency to wear. since the tendency to loss of even greater seen, the content of disintegrating agent is preferably 1-10 wt%.

The tableting pressure in the present invention is 100 to 900 Kgf, but the tablets were tableted at a tableting pressure of 100, 200, 300, 400 and 500 Kgf, and the physical properties were measured. and at 3kp above, in order to further improve the friction loss of, preferably to a tablet above 200 Kgf, to satisfy the disintegration, tablet hardness and grinding loss degree and tablet tableting pressure of 200~800Kgf It is preferable to do.

Study example 7
Using ingredients shown in Example 1 of Table 1, 300 Kgf previously subjected coated pestle and magnesium stearate mortar of a tableting machine with gauze deposited magnesium stearate is a lubricant, a tableting pressure except for using the procedure of example 1 to obtain intraoral rapid-disintegrating tablet of the tablet weight 200 mg.

Study Example 8
Using ingredients shown in Example 1 of Table 1, 400 Kgf previously subjected coated pestle and magnesium stearate mortar of a tableting machine with gauze deposited magnesium stearate is a lubricant, a tableting pressure except for using the procedure of example 1 to obtain intraoral rapid-disintegrating tablet of the tablet weight 200 mg.

Study Example 9
Using ingredients shown in Example 1 of Table 1, 500 Kgf previously subjected coated pestle and magnesium stearate mortar of a tableting machine with gauze deposited magnesium stearate is a lubricant, a tableting pressure except for using the procedure of example 1 to obtain intraoral rapid-disintegrating tablet of the tablet weight 200 mg.

Study example 10
Using ingredients shown in Example 1 of Table 1, 600 kgf previously subjected coated pestle and magnesium stearate mortar of a tableting machine with gauze deposited magnesium stearate is a lubricant, a tableting pressure except for using the procedure of example 1 to obtain intraoral rapid-disintegrating tablet of the tablet weight 200 mg.

That is, in the method for producing an intraoral rapidly disintegrating tablet according to claim 1 of the present invention , a polyvinylpyrrolidone K-30 ethanol solution is added to the particle core of 50 mesh crystal lactose,
Next, this polyvinylpyrrolidone K-30 ethanol solution is coated with ascorbic acid to coat the particle core with powder,
Next, the powder coating particles are dried and sized to form coating particles.
Next, granulated lactose, crystalline cellulose, crospovidone and maltitol are added to the coating particles and mixed to form a mixture.
Next, magnesium stearate is added to and mixed with this mixture, and then tableted to obtain an intraoral rapidly disintegrating tablet .

In the method for producing an intraoral rapidly disintegrating tablet according to claim 2 of the present invention , polyvinylpyrrolidone K-30 ethanol solution is added to the particle core of 50 mesh crystal lactose,
Next, this polyvinylpyrrolidone K-30 ethanol solution is coated with ascorbic acid to coat the particle core with powder,
Next, the powder coating particles are dried and sized to form coating particles.
Next, granulated lactose, crystalline cellulose, crospovidone and maltitol are added to the coating particles and mixed to form a mixture.
Next, this mixture is tableted by a tableting machine in which magnesium stearate is previously attached to the punch and mortar to obtain an intraoral rapidly disintegrating tablet.

The method for producing an orally rapidly disintegrating tablet according to the present invention comprises a drug containing a drug using a solution containing a water-soluble polymer in a core containing particles containing 5 to 40% by weight of 50 mesh crystal lactose. Powder coated particles with powder, 1-30 wt% crospovidone, carboxymethylcellulose, partially pregelatinized starch, low substituted hydroxypropylcellulose and corn starch disintegrant, 0.1-5 wt% stearic acid Magnesium, calcium stearate, stearic acid, stearyl alcohol, sucrose fatty acid ester, and talc lubricant are mixed, and tableted by the internal lubrication method or the external lubrication method at a tableting pressure of 100 to 900 Kgf to obtain tablets.

The content of consisting saccharides used in the present onset bright particles (nuclei) is 5 to 40% by weight relative to the amount of total tablet, in the content of 50 mesh crystalline lactose 0 wt% thereof tablets (same hardness) Compared with the disintegration degree of tablets containing crystalline lactose, the disintegration degree tends to be delayed, and the flowability of the powder for tableting is also inferior. When the content of crystalline lactose is 30% by weight or more, the tablet Since it is difficult to ensure a hardness of 3 kp and a tendency to increase the friability at 40% by weight is observed, the content of particles (core) made of saccharides is preferably 5 to 20% by weight.

Example 1
50 mesh (50M) crystalline lactose 10g was added to the mixer, where the addition of polyvinylpyrrolidone (PVP) K-30 (solids 0.045 g) in ethanol, over approximately about 2g once ascorbic acid therein This operation is repeated 5 times to perform powder coating. Next, the powder coating particles are dried and sized to form coating particles. Then, to the coated particles, granulated lactose (Asahi Kasei Co., Ltd. trade name: Super Tab) 16.5g, crystalline cellulose (Asahi Kasei Co., Ltd. trade name: Avicel PH102) 38.5g, crospovidone (BASF Takeda Vitamin (Co. ) 3 g of trade name: Kollidon CL) and 22 g of maltitol (Towa Kasei Kogyo Co., Ltd. trade name: powdered maltitol G3) are added and mixed to obtain a mixture. To this mixture was then added to and mixed with magnesium stearate 0.3 g, using a tableting machine to obtain intraoral rapid-disintegrating tablet of the tablet weight 200mg at tableting pressure 200 Kgf.

Comparative Example 1
10 g of ascorbic acid, 26.5 g of 200 mesh lactose, 38.5 g of crystalline cellulose, 3 g of crospovidone and 22 g of maltitol are charged into a mixer and mixed to obtain a uniform mixed powder. A PVPK-30 (solid content: 0.045 g) ethanol solution is added to the mixed powder, kneaded, granulated, dried, and sized. To this granulated product, 0.3 g of magnesium stearate as a lubricant was added and mixed, and a tableting machine was used to obtain an intraoral rapidly disintegrating tablet having a tablet weight of 200 mg at a tableting pressure of 200 kgf.

Study example 1
Ascorbic acid 10 g is mixed uniformly with 10 g of 200 mesh lactose and triturated. To this, 6.5 g of 200 mesh lactose, 38.5 g of crystalline cellulose, 3 g of crospovidone and 22 g of maltitol are added and mixed uniformly. In this mixed powder, 10 g of crystal lactose is blended and mixed so as not to break the crystals. A PVPK-30 (solid content: 0.045 g) ethanol solution is added thereto and kneaded. This is granulated, dried and then sized. To this granulated powder, 0.3 g of magnesium stearate was added and mixed, and a tableting machine was used to obtain an intraoral rapidly disintegrating tablet having a tablet weight of 200 mg at a tableting pressure of 200 kgf.

Test example 1
Tablets obtained in Examples 1 to 5 by the powder coating method using 50 mesh crystal lactose and Comparative Examples 1 to 5 by a conventional method using 200 mesh lactose without powder coating and the usual using crystal lactose Tests for disintegration, hardness, and friability were performed on the tablets obtained in Examination Examples 1 to 5 and the tablets of Examination Examples 6 to 10 obtained by the external lubrication method.

Therefore, the powder coating method using 50 mesh crystal lactose is an excellent method for producing an intraoral rapidly disintegrating tablet. On the other hand, when powdered lactose is formulated as an excipient without using crystalline lactose, it is difficult to produce an excellent intraoral rapidly disintegrating tablet with respect to tablet strength and tablet disintegration.

From the above results, the tablets obtained by the example in which ascorbic acid was powder-coated on 50 mesh crystal lactose were comparative examples in which the disintegration time and the disintegration time in the oral cavity were both produced in a conventional manner with powdered lactose. It was shortened compared with the tablet of the examination example manufactured by the conventional method using the tablet and crystallized lactose.

Therefore, the powder coating method using 50 mesh crystal lactose is an excellent method for producing an intraoral rapidly disintegrating tablet.

Claims (3)

Add a solution containing water-soluble polymer and / or water-insoluble polymer to the core of crystallized saccharide or granulated saccharide particles, and powder with drug or drug-containing powder A method for producing an orally rapidly disintegrating tablet, which comprises coating, adding a disintegrant and a lubricant to the powder-coated particles, and tableting. The content of the crystallized saccharide or granulated saccharide is 5 to 40% by weight based on the total weight of the tablet, the content of the disintegrant is 1 to 30% by weight, and the lubricant The method for producing an intraoral rapidly disintegrating tablet according to claim 1, wherein the content of is from 0.1 to 5% by weight. The tableting pressure in the case of the said tableting is 100-900Kgf, The manufacturing method of the intraoral quick disintegration tablet of any one of Claim 1 or 2 characterized by the above-mentioned.