JP2005029557A - Quickly disintegrating tablet in oral cavity and method for producing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a quickly disintegrating tablet in an oral cavity, capable of being produced without using complex producing processes or a special device and excellent as a medicine having a quick disintegrating property in the oral cavity on using, and a method for producing the same. <P>SOLUTION: The quickly disintegrating tablet in the oral cavity is obtained by blending a medicinally active ingredient with a medicinal carrier containing the following components (a) to (c) to form a mixture and then compression-forming the mixture. The components (a) to (c) are: (a) trehalose and/or sorbitol, (b) a synthetic aluminum silicate and (c) a disintegrating agent. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to an orally rapidly disintegrating tablet, and more specifically, an intraorally rapidly disintegrating tablet that is used in the fields of pharmaceuticals, foods, and the like and has good disintegrability in the oral cavity without water, and a method for producing the same About.

  As dosage forms of oral solid preparations in the fields of pharmaceuticals and foods, tablets, capsules, granules, powders and the like are generally known. However, few of these dosage forms are easy to handle and easy to take. For example, tablets and capsules become difficult to swallow as the size of the tablets and capsules increases. In addition, granules and powders have problems such as being peeled off when taken or entering between teeth. Further, all of these dosage forms require water at the time of taking, and there is a problem that it is difficult to take while sleeping in an emergency or a serious patient.

  As dosage forms that can be taken without water, chewable tablets are known that are used by chewing tablets, but what is currently offered is low in disintegration and suitable for elderly people and children with low chewing ability. Is hard to say.

  From this point of view, there is a demand for the development of a rapidly disintegrating tablet in the oral cavity that can be easily taken by patients without water and can be taken easily at any time and anywhere. Some techniques are also known.

  As a technique for producing such an orally rapidly disintegrating tablet, a conventional pharmaceutical ingredient is dissolved or suspended in an aqueous solvent and then filled into a pre-molded pocket of a blister pack, and this solution is freeze-dried or vacuumed. There are a method for producing by removing moisture by drying (see Patent Documents 1 to 3, etc.) and a method for producing the granules after compressing the moistened granules at low pressure (see Patent Documents 4 and 5). Are known. However, these production methods use special production equipment and require a long time for production, and thus have a disadvantage of inferior industrial productivity.

  Conventionally, a fast disintegrating tablet containing an inorganic compound and a saccharide (see Patent Document 6) and a fast disintegrating tablet containing a saccharide and a disintegrating agent (see Patent Document 7) have been known. It requires a special process or manufacturing equipment such as spray drying process, blending of co-pulverized product by grinding type pulverizer, and is usually the most widely used granulation method, wet granulation, dry granulation, The development of a formulation that can be produced by fluidized bed granulation was expected.

  From this point of view, it can be produced by a normal dry tableting method, and exhibits excellent disintegration and solubility in the oral cavity and has an appropriate strength that is not damaged in the preparation process and further in the distribution process. Development of the formulation which has is desired.

JP 53-44619 A Japanese Examined Patent Publication No. 62-50445 Japanese Patent Publication No. 5-812769 JP-A-6-218028 JP-A-8-19589 JP 2000-86537 A JP 2001-163770 A

  Therefore, the present invention provides an intraorally rapidly disintegrating tablet that can be manufactured without using a complicated manufacturing process or a special device, and is excellent as a pharmaceutical having rapid disintegration in the oral cavity at the time of use, and a manufacturing method thereof. It is to be an issue.

  As a result of intensive studies to solve the above problems, the inventors have obtained a mixture of an active pharmaceutical ingredient and a pharmaceutical carrier containing trehalose and / or sorbitol, synthetic aluminum silicate and a disintegrant at an appropriate ratio. By compression molding, without using a complicated manufacturing process or special equipment, in terms of hardness and disintegration time, the oral disintegration has the same or better performance than the preparation manufactured by a known method. It was found that tablets can be produced, and the present invention was completed.

That is, the present invention relates to an orally rapidly disintegrating tablet obtained by mixing a pharmaceutical active ingredient and a pharmaceutical carrier containing the following components (a) to (c) into a mixed product and then compressing the mixture. Is to provide.
(A) trehalose and / or sorbitol (b) synthetic aluminum silicate (c) disintegrant

In addition, the present invention is an intraoral rapid disintegration characterized by mixing an active pharmaceutical ingredient and a pharmaceutical carrier containing the following components (a) to (c) to form a mixture, and then compression-molding the mixture. The manufacturing method of a sexable tablet is provided.
(A) trehalose and / or sorbitol (b) synthetic aluminum silicate (c) disintegrant

  The intraoral rapidly disintegrating tablet of the present invention is a preparation that exhibits excellent disintegration and solubility in the oral cavity and has an appropriate hardness that is not damaged in the preparation process and distribution process. In addition, even if the drug which is an active pharmaceutical ingredient has bitterness, it is reduced by the strong or refreshing sweetness of the saccharide contained in the pharmaceutical carrier, so that it is excellent in ingestibility.

  Moreover, since the said tablet can be manufactured without using a complicated manufacturing process and a special apparatus, this invention is useful for industrial large-scale production.

  Therefore, according to the present invention, an intraoral quick disintegrating tablet having excellent moldability and disintegrating property and a method for producing the same can be provided.

  The intraoral rapidly disintegrating tablet (hereinafter referred to as “the present tablet”) of the present invention is composed of a pharmaceutical active ingredient and a pharmaceutical carrier.

The pharmaceutical active ingredient of this tablet can be used without particular limitation as long as it is a drug that can be administered orally without causing discomfort such as bitterness and astringency to the extent that it is not difficult to swallow in the oral cavity. Such drugs include antiemetics, emetics, antispasmodics, antitussives, bronchodilators, arrhythmic agents, cardiotonic agents, antacids, gastric digestives, peptic ulcers, intestinal adjusters, antistagnation agents, Antibacterial, antihypertensive, antihypertensive, antihypertensive, antihypertensive, antipyretic analgesic, antihypertensive agent, antihypertensive agent Examples include one or more drugs selected from psychotropic drugs, antiepileptic drugs, antihistamines, diabetes drugs, gout treatment drugs, osteoporosis drugs, antibiotics, tumor drugs, chemotherapeutic drugs, anti-parkinsonian drugs, etc. It is done. These drugs can be blended in a range that does not hinder the effects of the present invention, and the range in which these drugs can be blended varies depending on the properties of the drug, but can be blended in an amount of 50% by mass or less in the tablet.

  Specific examples of the drug include the following. Examples of the antiemetic include ondansetron hydrochloride and tropisetron hydrochloride. Examples of the emetic include metoclopramide. Examples of the antispasmodic agent include papaverine hydrochloride and baclofen. Examples of antitussive removal agents include dextromethorphan hydrobromide, potassium guaiacol sulfonate, and codeine phosphate. Examples of bronchodilators include theophylline, salbutamol sulfate, and tulobuterol hydrochloride. Examples of the arrhythmic agent include procainamide hydrochloride and propranolol hydrochloride. Examples of the cardiotonic agent include digoxin, aminophylline, ubidecarenone and the like. Examples of the antacid include sodium hydrogen carbonate, magnesium carbonate, magnesium aluminate metasilicate, and synthetic hydrotalcite. Examples of the healthy stomach digestive agent include diastase, pancreatin, cinnamon oil and the like. Examples of the peptic ulcer agent include famotidine, ranitidine, cimetidine, omeprazole and the like. Examples of the intestinal regulating agent include berberine chloride, spore-forming lactic acid bacteria, and bifidobacteria. Examples of the anti-blocking agent include loperamide hydrochloride. Examples of the bile agent include ursodeoxycholic acid. Examples of nourishing tonics include vitamins such as vitamin A, vitamin B, vitamin C and vitamin E, amino acids, oligosaccharides, herbal medicines and the like. Examples of the vasoconstrictor include phenylephrine hydrochloride and ephedrine hydrochloride. Examples of the vasodilator include isosorbide nitrate. Examples of the antihypertensive agent include angiotensin converting enzyme inhibitors such as captopril, α and β blockers such as labetalol hydrochloride, and calcium antagonists such as nifedipine and diltiazem hydrochloride. Diuretics include isosorbide and furosemide. Examples of the hyperlipidemia agent include pravastatin sodium and simvastatin. Examples of antipyretic analgesic / anti-inflammatory agents include aspirin, acetaminophen, ibuprofen, diclofenac sodium, indomethacin, ketoprofen and the like. Examples of the antipruritic agent include meclizine hydrochloride and dimenhydrinate. Examples of the hypnotic sedative include estazolam, nitrazepam and the like. Examples of the antidepressant include imipramine. Examples of the antianxiety drug include diazepam. Examples of psychotropic drugs include chlorpromazine, reserpine and the like. Examples of antiepileptic agents include carbamazepine and phenytoin. Examples of the antihistamine include diphenhydramine hydrochloride, chlorpheniramine maleate, mequitazine, and the like. Examples of the agent for diabetes include tolbutamide, troglidazone, acarbose and the like. Examples of the gout treatment agent include colchicine and allopurinol. Examples of the osteoporosis agent include ipriflavone. Antibiotics include, for example, cefaclor, ampicillin, josamycin, nalidixic acid and the like. Examples of the tumor drug include cyclophosphamide and fluorouracil. Examples of the chemotherapeutic agent include sulfamethoxazole. Examples of the antiparkinson agent include amantadine hydrochloride and levodopa.

  On the other hand, among the pharmaceutical carriers of this tablet, the component (a) trehalose and / or sorbitol is not particularly limited, and those manufactured by known methods can be used. These trehalose and sorbitol may be blended and used alone, or may be blended and used in combination. A preferable blending ratio when used in combination is 0.5 to 1.5 sorbitol with respect to trehalose 1 in the weight ratio thereof. The trehalose and / or sorbitol can be blended in the tablet in an amount of 10 to 90% by mass, preferably 20 to 80% by mass.

  In addition, among the pharmaceutical carriers of this tablet, the synthetic aluminum silicate as the component (b) can be used without any particular limitation, and any of commercially available heavy, light, and extra light grades should be used. Can do. This can be incorporated in the tablet in an amount of 1 to 30% by mass, preferably 5 to 25% by mass.

  Furthermore, the disintegrant which is a component (c) among the pharmaceutical carriers of this tablet can be used as long as it can be generally used in the pharmaceutical field. These disintegrants include crospovidone, croscarmellose sodium, carmellose calcium and low substituted hydroxypropylcellulose. Among these disintegrants, crospovidone, croscarmellose sodium and low-substituted hydroxypropylcellulose are preferred, crospovidone and croscarmellose sodium are more preferred, and crospovidone is particularly preferred. These disintegrants can be blended in the tablet in an amount of 1 to 30% by mass, preferably 5 to 20% by mass.

  In order to produce the tablet using each of the above-mentioned components, the above-mentioned pharmaceutically active ingredient and a pharmaceutical carrier are mixed to make a mixed product, and then compressed or molded, or the above-mentioned pharmaceutically active ingredient and the pharmaceutical carrier are mixed. Then, the mixed product may be further granulated to produce a granulated product, and the granulated product may be compression molded.

  In the above production, a mixed product is obtained by mixing the active pharmaceutical ingredient and the pharmaceutical carrier by a mixing method such as convection mixing, diffusion mixing or shear mixing. In these mixing methods, a mixing device such as a container rotation type mixer or a container fixed type mixer is used.

For compression molding of the mixed product thus obtained, for example, a method or an apparatus generally used for tablet molding such as a rotary tableting machine, a hydraulic press machine, or a single tableting machine can be used. Prior to this compression molding, the particle size of the mixed product is adjusted by subjecting it to operations necessary for production of general preparations such as sizing using a screen mill, low mill, hammer mill, and sieving using a vibrating sieve. When implemented, it can be molded at a relatively low compression pressure. Specific compression pressure include ^{500kg / cm 2 ~1000kg / cm 2} .

  On the other hand, in the production, the granulated product is obtained by granulating the mixed product. Examples of the granulation treatment include wet granulation treatment, dry flow granulation treatment, and fluidized bed granulation treatment. Among these granulation treatments, wet flow treatment is preferred.

  The wet granulation treatment is a treatment in which a pharmaceutically active ingredient and a pharmaceutical carrier are mixed, kneaded with a solvent, and then granulated. In this treatment, methods and apparatuses used for production of general preparations such as crushing granulation method, extrusion granulation method, stirring granulation method, and rolling granulation method can be used. In addition, as a solvent used in this treatment, an alcohol such as ethanol, methanol and isopropanol used for production of general preparations, and a solvent such as water can be used.

  The dry granulation treatment is a treatment in which a pharmaceutically active ingredient and a pharmaceutical carrier are mixed, sieved, and then granulated. In this treatment, a method or apparatus used for production of general preparations such as compression granulation can be used.

  The fluidized bed granulation process is a process in which a pharmaceutically active ingredient and a pharmaceutical carrier are mixed and then granulated while spraying a mixed solution of the solvent and a solvent and a binder or the like. In this treatment, a method or apparatus used for production of a general preparation such as a fluidized bed granulation method can be used.

For compression molding of the granulated product thus obtained, for example, a method or apparatus generally used for tablet formation such as a rotary tableting machine, a hydraulic press machine or a single tableting machine can be used. In this compression molding as well, as in the case of compression molding of the mixed product, it is possible to mold at a relatively low compression pressure if the granulated product is prepared after adjusting the particle size prior to compression molding. Specific compression pressure include ^{500kg / cm 2 ~1000kg / cm 2} .

  Furthermore, as long as there is no hindrance to the effect of the invention, the tablet may be blended with additives that can be generally used in the pharmaceutical field. These additives are mainly blended in a pharmaceutical carrier, but may be added to the granulated product after wet granulation. Examples of the additive include a binder, a flavoring agent, a fluidizing agent, a lubricant, a coloring agent, and a fragrance. Among these, examples of the binder include gum arabic powder, gelatin, pullulan, hydroxypropylcellulose, polyvinylpyrrolidone, hydroxypropylmethylcellulose, polyvinyl alcohol, methylcellulose, and the like, and examples of the corrigent include citric acid, tartaric acid, malic acid, ascorbine. Acid, sodium citrate, sodium chloride, l-menthol and the like can be mentioned. Examples of the fluidizing agent include hydrous silicon dioxide and light anhydrous silicic acid. Examples of the lubricant include magnesium stearate, calcium stearate, talc, and sucrose fatty acid ester. Examples of the colorant include edible. Examples include food colors such as Red No. 3, Edible Yellow No. 5, Edible Blue No. 1, and the like. Furthermore, examples of the flavor include orange, strawberry, yogurt, vanilla and menthol, and examples of the sweetener include aspartame, saccharin, dipotassium glycyrrhizinate and stevia. These additives can be used alone or in combination.

  The thus obtained tablet has an appropriate hardness that is not damaged in the preparation process and further in the distribution process, preferably a hardness of 3 kg or more, and exhibits excellent disintegration properties in the oral cavity. Further, this tablet has a disintegration time of 60 seconds or less in a disintegration test by the Japanese Pharmacopoeia.

  EXAMPLES Hereinafter, although an Example and a comparative example are given and this invention is demonstrated in more detail, these do not limit this invention at all.

The physical properties of the tablets obtained in Examples and Comparative Examples were evaluated by the following test methods.
(1) Hardness test:
The test was carried out using a tablet hardness meter (KHT-20: manufactured by Fujiwara Seisakusho). The number of tests was 10 tablets, and the average value of the hardness was evaluated.
(2) Disintegration test:
With reference to the disintegration test by the Japanese Pharmacopoeia, the test was conducted using a disintegration tester (NT-1HM: manufactured by Toyama Sangyo). The number of tests was 6 tablets, and the average value of the time required until disintegration was evaluated.

Example 1
Manufacture of tablets (1):
After mixing 62.5 g of meclizine hydrochloride, 722.5 g of trehalose, 150 g of synthetic aluminum silicate, 5 g of aspartame, 5 g of acesulfame potassium and 50 g of crospovidone, 350 g of ethanol was gradually added and kneaded. I got a thing. This kneaded product was granulated with an extrusion granulator and then dried with a shelf dryer to obtain a granulated product. After granulating this granulated product, 5 g of magnesium stearate was added and mixed to obtain a mixture. This mixture was tableted at a compression pressure of 700 kg / cm ² using a rotary tableting device to obtain 400 mg tablets containing 25 mg of meclizine hydrochloride per tablet.

Example 2
Tablet production (2):
After mixing 62.5 g of meclizine hydrochloride, 722.5 g of sorbitol, 150 g of synthetic aluminum silicate, 5 g of aspartame, 5 g of acesulfame potassium and 50 g of crospovidone, 350 g of ethanol was gradually added and kneaded. I got a thing. This kneaded product was granulated with an extrusion granulator and then dried with a shelf dryer to obtain a granulated product. After granulating this granulated product, 5 g of magnesium stearate was added and mixed to obtain a mixture. This mixture was tableted at a compression pressure of 700 kg / cm ² using a rotary tableting device to obtain 400 mg tablets containing 25 mg of meclizine hydrochloride per tablet.

Comparative Example 1
Production of comparative tablets (1):
After mixing 62.5 g of meclizine hydrochloride, 722.5 g of erythritol, 150 g of synthetic aluminum silicate, 5 g of aspartame, 5 g of acesulfame potassium and 50 g of crospovidone, 350 g of ethanol was gradually added and kneaded. I got a thing. This kneaded product was granulated with an extrusion granulator and then dried with a shelf dryer to obtain a granulated product. After granulating the granulated product, 5 g of magnesium stearate was added and mixed to obtain a mixture. This mixture was tableted at a compression pressure of 700 kg / cm ² using a rotary tableting device to obtain 400 mg tablets containing 25 mg of meclizine hydrochloride per tablet.

Comparative Example 2
Production of comparative tablets (2):
After mixing 62.5 g of meclizine hydrochloride, 722.5 g of powdered reduced maltose starch syrup, 150 g of synthetic aluminum silicate, 5 g of aspartame, 5 g of acesulfame potassium and 50 g of crospovidone, 350 g of ethanol was gradually added and kneaded. , Got a kneaded product. This kneaded product was granulated with an extrusion granulator and then dried with a shelf dryer to obtain a granulated product. After granulating this granulated product, 5 g of magnesium stearate was added and mixed to obtain a mixture. This mixture was tableted at a compression pressure of 700 kg / cm ² using a rotary tableting device to obtain 400 mg tablets containing 25 mg of meclizine hydrochloride per tablet.

Test example 1
Performance test (1):
The component compositions of the tablets of Examples 1 and 2 and Comparative Examples 1 and 2 and the hardness test and disintegration test results of these tablets are shown in Table 1.

  From this result, it was found that the tablets using Examples (1 and 2) using trehalose or sorbitol showed excellent characteristics as an intraoral fast disintegrating tablet having a hardness of 3 kg or more and a disintegration time within 60 seconds. However, it was found that the tablets using erythritol or powdered reduced maltose starch syrup (Comparative Examples 1 and 2) have increased hardness and delayed disintegration time, and cannot satisfy the characteristics as an orally rapidly disintegrating tablet. .

Comparative Example 3
Comparative tablet (3):
After mixing 62.5 g of meclizine hydrochloride, 722.5 g of trehalose, 150 g of crystalline cellulose, 5 g of aspartame, 5 g of acesulfame potassium and 50 g of crospovidone, 350 g of ethanol was gradually added and kneaded. Obtained. This kneaded product was granulated with an extrusion granulator and then dried with a shelf dryer to obtain a granulated product. After granulating this granulated product, 5 g of magnesium stearate was added and mixed to obtain a mixture. This mixture was tableted at a compression pressure of 700 kg / cm ² using a rotary tableting device to obtain 400 mg tablets containing 25 mg of meclizine hydrochloride per tablet.

Comparative Example 4
Comparative tablet (4):
After mixing 62.5 g of meclizine hydrochloride, 722.5 g of trehalose, 150 g of partially pregelatinized starch, 5 g of aspartame, 5 g of acesulfame potassium and 50 g of crospovidone, 350 g of ethanol was gradually added and kneaded. I got a thing. This kneaded product was granulated with an extrusion granulator and then dried with a shelf dryer to obtain a granulated product. After granulating this granulated product, 5 g of magnesium stearate was added and mixed to obtain a mixture. This mixture was tableted at a compression pressure of 700 kg / cm ² using a rotary tableting device to obtain 400 mg tablets containing 25 mg of meclizine hydrochloride per tablet.

Comparative Example 5
Comparative tablet (5):
After mixing 62.5 g of meclizine hydrochloride, 722.5 g of trehalose, 150 g of hydroxypropyl starch, 5 g of aspartame, 5 g of acesulfame potassium and 50 g of crospovidone, 350 g of ethanol was gradually added and kneaded. Got. This kneaded product was granulated with an extrusion granulator and then dried with a shelf dryer to obtain a granulated product. After granulating this granulated product, 5 g of magnesium stearate was added and mixed to obtain a mixture. This mixture was tableted at a compression pressure of 700 kg / cm ² using a rotary tableting device to obtain 400 mg tablets containing 25 mg of meclizine hydrochloride per tablet.

Test example 2
Performance test (2):
The component compositions of Comparative Examples 3 to 5 and the results of the hardness test and disintegration test of these tablets and the tablet of Example 1 are shown in Table 2.

  From these results, when crystalline cellulose, partially pregelatinized starch and hydroxypropyl starch were used in place of the synthetic aluminum silicate in the tablet of Example 1 (Comparative Examples 3 to 5), an increase in hardness and a delay in disintegration time were recognized. As a result, it was found that the characteristics as an intraoral rapidly disintegrating tablet cannot be satisfied.

Example 3
Production of tablets (3):
After mixing 62.5 g of meclizine hydrochloride, 722.5 g of trehalose, 150 g of synthetic aluminum silicate, 5 g of aspartame, 5 g of acesulfame potassium and 50 g of croscarmellose sodium, 350 g of ethanol was gradually added and kneaded. A kneaded product was obtained. This kneaded product was granulated with an extrusion granulator and then dried with a shelf dryer to obtain a granulated product. After granulating this granulated product, 5 g of magnesium stearate was added and mixed to obtain a mixture. This mixture was tableted at a compression pressure of 700 kg / cm ² using a rotary tableting device to obtain 400 mg tablets containing 25 mg of meclizine hydrochloride per tablet.

Example 4
Tablet manufacture (4):
After mixing 62.5 g of meclizine hydrochloride, 722.5 g of trehalose, 150 g of synthetic aluminum silicate, 5 g of aspartame, 5 g of acesulfame potassium and 50 g of carmellose calcium, 350 g of ethanol was gradually added and kneaded. A compound was obtained. This kneaded product was granulated with an extrusion granulator and then dried with a shelf dryer to obtain a granulated product. After granulating this granulated product, 5 g of magnesium stearate was added and mixed to obtain a mixture. This mixture was tableted at a compression pressure of 700 kg / cm ² using a rotary tableting device to obtain 400 mg tablets containing 25 mg of meclizine hydrochloride per tablet.

Example 5
Tablet manufacture (5):
62.5 g of meclizine hydrochloride, 722.5 g of trehalose, 150 g of synthetic aluminum silicate, 5 g of aspartame, 5 g of acesulfame potassium and 50 g of low-substituted hydroxypropylcellulose were mixed with a stirring granulator, and 350 g of ethanol was gradually added and kneaded. And kneaded material was obtained. This kneaded product was granulated with an extrusion granulator and then dried with a shelf dryer to obtain a granulated product. After granulating this granulated product, 5 g of magnesium stearate was added and mixed to obtain a mixture. This mixture was tableted at a compression pressure of 700 kg / cm ² using a rotary tableting device to obtain 400 mg tablets containing 25 mg of meclizine hydrochloride per tablet.

Comparative Example 6
Comparative tablet (6):
62.5 g of meclizine hydrochloride, 772.5 g of trehalose, 150 g of synthetic aluminum silicate, 5 g of aspartame and 5 g of acesulfame potassium were mixed with a stirring granulator, and then 350 g of ethanol was gradually added and kneaded to obtain a kneaded product. . This kneaded product was granulated with an extrusion granulator and then dried with a shelf dryer to obtain a granulated product. After granulating this granulated product, 5 g of magnesium stearate was added and mixed to obtain a mixture. This mixture was tableted using a rotary tableting machine at a compression pressure of 700 kg / cm ² to obtain 400 mg tablets containing 25 mg of meclizine hydrochloride per tablet.

Test example 3
Performance test (3):
The component compositions of Examples 3 to 5 and Comparative Example 6, and the results of the hardness test and disintegration test of these tablets and the tablet of Example 1 are shown together in Table 3.

  From these results, when disintegrating agents of croscarmellose sodium, carmellose calcium and low-substituted hydroxypropylcellulose were used instead of crospovidone which is the disintegrant of the tablet of Example 1 (Examples 3 to 5) However, it has been found that the tablet exhibits excellent characteristics as an intraoral fast disintegrating tablet, having a hardness of 3 kg or more and a disintegration time within 60 seconds. However, in the case where no disintegrant was blended (Comparative Example 6), it was found that the disintegration time was 60 seconds or longer, and the characteristics as an intraoral fast disintegrating tablet could not be satisfied.

  From the above test results, it was found that the intraoral fast disintegrating tablet of the present invention must contain trehalose and / or sorbitol, synthetic aluminum silicate, and a disintegrant.

Example 6
Tablet production (6):
62.5 g of meclizine hydrochloride, 722.5 g of trehalose, 150 g of synthetic aluminum silicate, 5 g of aspartame, 5 g of acesulfame potassium, 50 g of crospovidone and 5 g of magnesium stearate were mixed with a stirrer to obtain a mixture. After the mixture was sized, it was tableted using a rotary tableting machine at a compression pressure of 700 kg / cm ² to obtain 400 mg tablets containing 25 mg of meclizine hydrochloride per tablet.

Example 7
Tablet production (7):
62.5 g of meclizine hydrochloride, 722.5 g of sorbitol, 150 g of synthetic aluminum silicate, 5 g of aspartame, 5 g of acesulfame potassium, 50 g of crospovidone and 5 g of magnesium stearate were mixed with a stirrer to obtain a mixture. After the mixture was sized, it was tableted using a rotary tableting machine at a compression pressure of 700 kg / cm ² to obtain 400 mg tablets containing 25 mg of meclizine hydrochloride per tablet.

Test example 4
Performance test (4):
The component compositions of Examples 1, 2, 6, and 7 and the results of the hardness test and disintegration test of these tablets and the tablet of Example 1 are shown together in Table 4.

  From this result, the formulation of Example 1 or Example 2 is the same as that of Example 1 and Example 6 or Example 7 that has not undergone the granulation step has a hardness of 3 kg or more and a disintegration time of 60 seconds or less. It was found that it exhibits excellent properties as an internal fast disintegrating tablet.

  From the above test results, it was found that the intraoral rapidly disintegrating tablet of the present invention has the same performance as the tablet obtained through the granulation step without performing the granulation step.

  The intraoral rapidly disintegrating tablet of the present invention is a preparation that exhibits excellent disintegration and solubility in the oral cavity and has an appropriate hardness that is not damaged in the preparation process and distribution process. Moreover, the said tablet can be manufactured without using a complicated manufacturing process and a special apparatus.

Therefore, the present invention is extremely useful for industrial large-scale production of intraoral rapidly disintegrating tablets.

more than

Claims (8)

An intraoral rapidly disintegrating tablet obtained by mixing a pharmaceutical active ingredient and a pharmaceutical carrier containing the following components (a) to (c) to obtain a mixed product, and then compression molding the mixture.
(A) trehalose and / or sorbitol (b) synthetic aluminum silicate (c) disintegrant An intraoral rapidly disintegrating tablet obtained by granulating a pharmaceutical active ingredient and a pharmaceutical carrier containing the following components (a) to (c) to produce a granulated product, and then compressing the granulated product .
(A) trehalose and / or sorbitol (b) synthetic aluminum silicate (c) disintegrant   10 to 90% by mass of trehalose and / or sorbitol as component (a), 1 to 30% by mass of synthetic aluminum silicate as component (b), and 1 to 30% by mass of disintegrant as component (c). 3. Orally rapidly disintegrating tablet according to 1 or 2.   The disintegrant of component (c) is at least one disintegrant selected from crospovidone, croscarmellose sodium, carmellose calcium and low-substituted hydroxypropylcellulose. Orally rapidly disintegrating tablet.   The tablet rapid disintegration tablet according to any one of claims 1 to 4, wherein the tablet hardness is 3 kg or more.   The rapidly disintegrating tablet in the oral cavity according to any one of claims 1 to 5, wherein a disintegration time in a disintegration test by the Japanese Pharmacopoeia is within 60 seconds. A method for producing an orally rapidly disintegrating tablet, comprising mixing an active pharmaceutical ingredient and a pharmaceutical carrier containing the following components (a) to (c) to form a mixture, and then compressing the mixture.
(A) trehalose and / or sorbitol (b) synthetic aluminum silicate (c) disintegrant An intraoral quick disintegration characterized by producing a granulated product by granulating a pharmaceutical active ingredient and a pharmaceutical carrier containing the following components (a) to (c), and then compression-molding the granulated product: Tablet manufacturing method.
(A) trehalose and / or sorbitol (b) synthetic aluminum silicate (c) disintegrant