JP6958856B2 - tablet - Google Patents

Description

The present invention relates to tablets and methods for producing the same, and more particularly to tablets containing famciclovir or a salt thereof.

The larger the tablet, the more difficult it is to take, and especially for children, the elderly, people with dysphagia, etc., the larger the tablet, the more difficult it is to take. Therefore, the smaller the tablet, the less difficult it is to take and the better the feeling of taking the tablet. However, as the tablet becomes smaller, the amount of ingredients that can be blended also decreases, so that a therapeutically effective amount may not be blended. Therefore, it is required to reduce the size while maintaining the blending amount of the components. However, simply increasing the tableting pressure and compressing it further to reduce its size may result in an unnecessarily high hardness (that is, a tablet that is too hard), which may affect the elution property and the like. In addition, the type and amount of the active ingredient and the type and amount of additives such as disintegrants and excipients may adversely affect the dissolution property, etc., and the tablet-containing component may be simply reduced. not.

Famciclovir is known as an active ingredient of therapeutic agents for herpes simplex, herpes zoster and the like. Shingles has a larger number of patients than herpes simplex and is the main target disease for famciclovir. The age composition of patients with herpes zoster is relatively high, and it is said that nearly half of them are over 60 years old.

For adults, the dosage of famciclovir is 250 mg (herpes simplex) or 500 mg (shingles) at a time, and the amount of active ingredient to be taken at a time is It is a relatively large amount. Therefore, there is a problem that the tablets developed so far are relatively large in size.

Famciclovir (registered trademark) tablet 250 mg (Japanese standard product classification number: 87625) Pharmaceutical interview form November 2016 (revised 10th edition)

The present invention provides tablets containing famciclovir or a salt thereof as an active ingredient, which are smaller (meaning that the content of the active ingredient is higher in the present application) and have appropriate elution. Make it an issue.

The present inventors have increased the mass of one tablet by further reducing the content of ingredients (additives) other than the active ingredient, that is, by increasing the content ratio of the active ingredient, while proceeding with research in view of the problems. The focus was on the technique of reducing and obtaining smaller tablets. However, in the search for this method, the present inventors simply adopted the method of reducing the amount of additives, which caused the raw material to stick to the mortar and pestle at the time of tableting. It has been found that there is a problem that the obtained tablet is damaged (binding) and a problem that the dissolution property is deteriorated.

As a result of further diligent research based on these problems, the present inventors have added (A) famcyclovir or a salt thereof to 100% by mass of tablets in an amount of 75 to 81% by mass in terms of famcyclovir amount. By blending (B) lactose hydrate in an amount of 2 to 6% by mass, (C) croscarmellose or a salt thereof in an amount of 8 to 15% by mass, and (D) a lubricant in an amount of 2 to 4% by mass. It has been found that it is possible to obtain a tablet which is smaller, has appropriate dissolution property, and has less tableting trouble such as binding. As a result of further research based on this finding, the present invention has been completed.

That is, the present invention includes the following aspects.

Item 1.
For 100% by mass of tablets
(A) 75 to 81% by mass of famciclovir or a salt thereof in terms of famciclovir amount,
(B) 2 to 6% by mass of lactose hydrate,
(C) croscarmellose or a salt thereof in an amount of 8 to 15% by mass, and (D) a lubricant in an amount of 2 to 4% by mass.
Contains, tablets.

Item 2.
Item 2. The tablet according to Item 1, which contains 0.2 to 5% by mass of (E) a fluidizing agent with respect to 100% by mass of the tablet.

Item 3.
Item 2. The tablet according to Item 1 or 2, which contains 0.2 to 5% by mass of the (F) binder with respect to 100% by mass of the tablet.

Item 4.
Item 2. The tablet according to any one of Items 1 to 3, wherein the granule is obtained by a granule compression method and the granule is a granule obtained by a stirring granulation method.

Item 5.
Item 2. The tablet according to Item 4, which is obtained by a method in which a part of the component (C) is added in a powder state after granulation.

Item 6.
Item 5. The tablet according to Item 5, wherein the amount of the component (C) added after granulation is 50 to 67% by mass with respect to 100% by mass of the total amount of the component (C) contained in the tablet.

Item 7.
Item 2. The tablet according to any one of Items 1 to 6, which is a coated tablet.

Item 8.
Item 2. The tablet according to any one of Items 1 to 7, wherein the content of the component (A) in one tablet is 245 to 255 mg.

Item 9.
Item 2. The tablet according to any one of Items 1 to 7, wherein the content of the component (A) in one tablet is 490 to 510 mg.

Item 10.
Item 2. The tablet according to any one of Items 1 to 9, wherein the content of the component (A) in one tablet is 77 to 79% by weight.

Item 11.
Item 2. The method for producing a tablet according to any one of Items 1 to 10, which comprises a step of producing using a granule compression method.

Item 12.
Item 2. The production method according to Item 11, wherein the granulation method used in the granule compression method is a stirring granulation method.

Item 13.
Item 2. The production method according to Item 11 or 12, wherein a part of the component (C) is added in a powder state after granulation.

Item 14.
Item 13. The production method according to Item 13, wherein the amount of the component (C) added after granulation is 50 to 67% by mass with respect to 100% by mass of the total amount of the component (C) contained in the tablet.

INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide a tablet containing famciclovir or a salt thereof as an active ingredient, which is smaller, has appropriate dissolution property, and has less tableting trouble such as binding.

In the present specification, the expressions "contains" and "contains" include the concepts of "contains", "contains", "substantially consists" and "consists of only".

1. 1. Tablets In one aspect of the present invention, (A) famcyclovir or a salt thereof, 75 to 81% by mass in terms of femcyclovir amount, and (B) lactose hydrate are added to 100% by mass of tablets. Tablets containing up to 6% by mass, (C) croscarmellose or a salt thereof in an amount of 8 to 15% by mass, and (D) a lubricant in an amount of 2 to 4% by mass (in the present specification, "tablets of the present invention"). It may be shown as.). This will be described below.

Unless otherwise specified, the term "tablet" in the present invention means a solid preparation having a fixed shape to be orally administered, and includes ordinary tablets, orally disintegrating tablets, chewable tablets, troche tablets, and the like. Sublingual tablets, foam tablets, dispersion tablets, dissolution tablets, and sustained-release tablets are included, and are preferably ordinary tablets. Further, the tablet targeted by the present invention includes a single-layer tablet having a single-layer structure and a multi-layer tablet having a plurality of layers of two or more layers, and is preferably a single-layer tablet. Further, the tablets of the present invention include uncoated uncoated tablets (naked tablets), sugar-coated tablets, gelatin-encapsulated tablets and film-coated tablets (including enteric-coated tablets and gastric-coated tablets, also referred to as "film-coated tablets"). (These are also collectively referred to as "coated tablets" as opposed to uncoated tablets), and are preferably film-coated tablets.

(A) Famciclovir or its salt (component A)
Famciclovir is a known compound known to be effective in treating herpes simplex and shingles. The structural formula of famciclovir is shown below.

The salt of famcyclovir is not particularly limited as long as it is a pharmaceutically acceptable salt, and for example, hydrochloride, nitrate, sulfate, hydrobromide, phosphate, carbonate, acetate, lactate. , And at least one selected from the group consisting of citrates. These acid addition salts can be produced according to a conventional method.

The A component may be one kind alone or a combination of two or more kinds.

The content of component A is 75 to 81% by mass in terms of famciclovir amount with respect to 100% by mass of the tablet of the present invention. The content is preferably 76 to 80% by mass, more preferably 77 to 79% by mass, and further preferably 77.5 to 78.5% by mass.

The content of the component A in one tablet of the present invention is not particularly limited, and is, for example, 245 to 255 mg and 490 to 510 mg in terms of the amount of famciclovir.

(B) Lactose hydrate (B component)
The lactose hydrate is not particularly limited, and for example, a commercially available product can be purchased and used. Examples of commercially available products include PharmatoseR / 200M (manufactured by DFE).

The B component may be a single type or a combination of two or more types.

The content of component B is 2 to 6% by mass with respect to 100% by mass of the tablet of the present invention. The content is preferably 2.5 to 5% by mass, more preferably 3 to 4.5% by mass, still more preferably 3.4 to 4.2% by mass, and even more preferably 3.7 to 3.9% by mass.

(C) Croscarmellose or its salt (C component)
The croscarmellose or a salt thereof is not particularly limited, and for example, a commercially available product can be purchased and used. Examples of commercially available products include Ac-Di-Sol (manufactured by FMC International).

The salt of croscarmellose is not particularly limited as long as it is a pharmaceutically acceptable salt, and is, for example, an alkali metal salt (for example, sodium salt, potassium salt, etc.) and an alkaline earth metal salt (for example, calcium salt, magnesium salt, etc.). Metal salts such as); ammonium salts; organic base salts (eg, trimethylamine salts, triethylamine salts, pyridine salts, picolin salts, dicyclohexylamine salts, ethylenediamine salts, N, N'-dibenzylethylenediamine salts, tris (hydroxymethyl) Aminomethane salt, ethanolamine salt, etc.) can be exemplified. Among these, an alkali metal salt is preferable, and a sodium salt is more preferable.

The C component may be a single type or a combination of two or more types.

The content of the C component is 8 to 15% by mass with respect to 100% by mass of the tablet of the present invention. The content is preferably 8.5 to 13% by mass, more preferably 9 to 11% by mass, still more preferably 9.5 to 10.5% by mass, and even more preferably 9.8 to 10.2% by mass.

(D) Lubricating agent (D component)
The lubricant is not particularly limited, and is, for example, stearic acid, magnesium stearate, calcium stearate, talc, sucrose fatty acid ester, glycerin fatty acid ester, hydrogenated oil, polyethylene glycol, dimethylpolysiloxane, carnauba wax, sodium lauryl sulfate, and beeswax. , Sarashimitsuro and the like. Of these lubricants, magnesium stearate is preferred.

The D component may be a single type or a combination of two or more types.

The content of the D component is 2 to 4% by mass with respect to 100% by mass of the tablet of the present invention. The content is preferably 2.5 to 3.5% by mass, more preferably 2.8 to 3.2% by mass, and further preferably 2.9 to 3.1% by mass.

(E) Fluidizer (E component)
The tablets of the present invention preferably contain a fluidizing agent. The fluidizing agent is not particularly limited, and examples thereof include light anhydrous silicic acid, talc, and hydrous silicon dioxide. Among these fluidizing agents, light anhydrous silicic acid is preferable.

The E component may be one kind alone or a combination of two or more kinds.

The content of the E component is not particularly limited. The content is preferably 0.2 to 5% by mass with respect to 100% by mass of the tablet of the present invention. The content is preferably 1 to 3.5% by mass, more preferably 1.5 to 2.5% by mass, still more preferably 1.8 to 2.2% by mass, and even more preferably 1.9 to 2.1% by mass.

(F) Binder (F component)
The tablets of the present invention preferably contain a binder. The binder is not particularly limited, and is, for example, a cellulose derivative such as methyl cellulose, ethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hypromellose, carboxymethyl cellulose; crystalline cellulose, polyvinyl alcohol, polyvinylpyrrolidone (povidone), vinylpyrrolidone copolymer (copolyvidone). ), Acrylic polymer, gelatin, gum arabic, purulan, canten, tragant, sodium alginate, propylene glycol alginate, pregelatinized starch, dextrin, macrogol, sucrose and the like. Of these binders, hydroxypropyl cellulose is preferred.

The F component may be one kind alone or a combination of two or more kinds.

The content of the F component is not particularly limited. The content is preferably 0.2 to 5% by mass with respect to 100% by mass of the tablet of the present invention. The content is preferably 0.7 to 3% by mass, more preferably 1 to 2% by mass, still more preferably 1.3 to 1.8% by mass, and even more preferably 1.4 to 1.6% by mass.

(G) Other components (G component)
In addition to the above components, the tablet of the present invention may contain other components such as conventional carrier components and additives as long as the effects of the present invention are not impaired. Examples of the other components include excipients other than component B, disintegrants other than component C, antioxidants, preservatives, solubilizers, surfactants, plasticizers, pH regulators, colorants, and flavoring agents. Examples thereof include sweeteners, flavoring agents, adsorbents, preservatives, and wetting agents.

The G component may be a single type or a combination of two or more types.

Excipients include, for example, sugar alcohols (D-sorbitol, erythritol, xylitol, powder-reduced malt sugar candy, etc.), sugars (lactose, glucose, fructose, sucrose, etc.), crystalline cellulose, powdered cellulose, starches (valley starch, potato starch, etc.). Corn starch, wheat starch, etc.), dextrin, β-cyclodextrin, carmellose sodium, hydrous silicon dioxide, silicon dioxide, precipitated calcium carbonate, anhydrous calcium hydrogen phosphate, magnesium oxide, titanium oxide, calcium lactate, aluminic acid metasilicate Examples include magnesium, synthetic hydrotalcite, starch, and kaolin. These excipients can be used alone or in combination of two or more. When these excipients are used, the total content of these excipients and component B is, for example, 2 to 6% by mass, preferably 2.5 to 5% by mass, based on 100% by mass of the tablet of the present invention. It is more preferably 3 to 4.5% by mass, further preferably 3.4 to 4.2% by mass, and even more preferably 3.7 to 3.9% by mass.

Examples of the disintegrant include carboxymethyl celluloses (for example, carmellose, carmellose sodium, carmellose calcium, crystalline cellulose / carmellose sodium, etc.), carboxymethyl starches (for example, carboxymethyl starch sodium, etc.), crospovidone, and low. Examples thereof include degree of substitution hydroxypropyl cellulose, low degree of substitution hydroxymethyl starch sodium, starches (such as corn starch), alginic acid, and bentonite. These disintegrants may be used alone or in any combination of two or more. When these disintegrants are used, the total content of these excipients and the C component is, for example, 8 to 15% by mass, preferably 8.5 to 13% by mass, based on 100% by mass of the tablet of the present invention. It is preferably 9 to 11% by mass, more preferably 9.5 to 10.5% by mass, and even more preferably 9.8 to 10.2% by mass.

Examples of the solubilizing agent include magnesium oxide, calcium oxide, sodium citrate, magnesium chloride, sodium carbonate, sodium hydrogen carbonate and the like.

Surfactants include polyoxyethylene hydrogenated castor oil, polyoxyethylene polyoxypropylene, polyoxyethylene fatty acid ester, glycerin monostearate, sorbitan fatty acid ester (sorbitan monostearate, sorbitan monolaurate, etc.), polysorbates, lauryl. Nonionic surfactants such as sodium alkylsulfate and anionic surfactants such as sodium sulfate, macrogols, and sucrose fatty acid esters can be exemplified.

Examples of the pH adjuster include organic acids such as glycine, sodium hydrogencarbonate, calcium hydrogenphosphate, sodium hydrogenphosphate, acetic acid, succinic acid, tartaric acid, fumaric acid and citric acid, or salts thereof.

Colorants include water-soluble colorants such as turmeric extract, riboflavin, carotene solution, tar pigment, and caramel, as well as titanium oxide, iron oxide (yellow iron oxide, iron sesquioxide, yellow sesquioxide, red iron oxide, etc.). And water-insoluble colorants such as tar-based dyes (aluminum salts such as lake dyes) can be mentioned.

Sweeteners such as aspartame and stevia, ascorbic acid, menthol, crude kanzo extract, simple syrup, etc. as flavoring agents; natural or synthetic sweeteners such as sucrose, D-sorbitol, xylitol, aspartame; As the fragrance, menthol, mint and the like can be exemplified without limitation.

(H) Coating Layer As described above, the tablet of the present invention is a coating tablet (sugar-coated tablet, gelatin-encapsulated tablet, film-coated tablet) having a coating layer (coating layer) on its surface even if it is an uncoated tablet. You may. The tablet of the present invention is preferably a coated tablet, more preferably a film-coated tablet.

When the tablet of the present invention is a coated tablet, the coating agent used for forming the coating layer can be appropriately selected and used according to the purpose based on the common general technical knowledge in the art. For example, sugars such as sucrose, D-mannitol, erythritol, sorbitol, xylitol, and trehalose are used to prepare sugar-coated tablets. For the preparation of film-coated tablets, water-soluble coating agents such as hydroxypropyl cellulose (HPC), hypromellose, polyvinyl alcohol, polyethylene glycol, and purulan; hypromellose phthalate (HPMCP), hydroxypropyl methylcellulose acetate succinate (HPMCAS). ), Carboxymethyl ethyl cellulose (CMEC), methacrylic acid copolymer, ceracefate (cellulose phthalate acetate) and enteric coating agents such as cellac; gastrosoluble coatings such as polyvinyl acetal diethylaminoacetate, aminoalkylmethacrylate copolymer, polyvinylacetal diethylaminoacetate Agents; Polymer compounds such as sustained release coatings such as ethyl cellulose and aminoalkyl methacrylate copolymers are used.

If necessary, these coating agents may be blended with a colorant, a flavoring agent, a sweetening agent, a flavoring agent, a light-shielding agent, a plasticizer, and the like. The blending ratio of these colorants and the like in the coating layer is not limited, but is appropriately adjusted so as to be in the range of 0.0001 to 20% by mass in 100% by mass of the total amount of the components forming the coating layer.

In the coated tablet, the ratio of the coating layer (coating layer, coating) is not limited, but can be appropriately selected from the range of 0.5 to 10% by mass with respect to 100% by mass of the tablet of the present invention. It is preferably 0.5 to 5% by mass, more preferably 1 to 2% by mass, and even more preferably 1.3 to 1.7% by mass.

2. Method for Producing Tablets The tablets of the present invention can be preferably produced by a granule compression method (particularly, a wet granule compression method). Specifically, the tablets of the present invention are preferably
(Step I) A component, B component, C component, and if necessary, other components are powder-mixed, and a binder (F component) prepared in a solution form is added thereto for granulation (wet preparation). Grain) process,
(Step II) The step of drying and sizing the granulated product obtained in Step I,
(Step III) A step of mixing the sized product obtained in Step II with the D component and, if necessary, other components (for example, E component, C component, etc.), and (Step IV) Obtained in Step III. The resulting mixture can be obtained by a production method including a step of compression molding (locking).

Process I (mixing / granulation process)
The mixing of each component may be any method as long as the powders of these components can be uniformly mixed, and the mixing method is not particularly limited. A method of mixing using a mixer such as a rotary type mixer (for example, V type mixer, double conical type mixer), a fixed type mixer (ribbon type mixer, screw type mixer), etc., without limitation. It can be exemplified.

In step I, it is preferable to add only a part of the C component. The rest is preferably added in step III as described below. The amount of the C component added in step I is preferably 33 to 50% by mass, more preferably 35 to 45% by mass, still more preferably 38 to 42, based on 100% by mass of the total amount of the C component contained in the tablet. The amount is mass%.

The granulation method may be a wet granulation method generally used in the art. For example, a solution-like binder is added to a raw material powder mixture and kneaded, and the kneaded product is extruded from a screen for molding. Extrusion granulation method, which is a method of granulation; crushing, which is a method of cutting a kneaded mass prepared by kneading by the above method with a rotary blade of a granulator and ejecting it from the outer screw eyes by centrifugal force. Granulation method: A rolling granulation method in which a solution-like binder is added to a raw material powder mixture and the humidified powder is subjected to rotational motion or vibration to agglomerate the powder to obtain particles that are close to spherical. Flowing layer granulation method, which is a method of granulating by spraying a solution-like binder onto the granulated material. An example of a stirring granulation method in which a liquid is added to aggregate the raw material powders and granules into a spherical shape can be exemplified without limitation. Among these, a stirring granulation method (particularly, a high-speed stirring granulation method) is preferable.

Process II (drying / sizing process)
For drying the granules prepared in step I, a drying method commonly used in the art is adopted, for example, a parallel flow box type dryer, a ventilation flow box type dryer, a fluidized bed dryer, and a vacuum. This can be done using various drying devices such as a type dryer.

The sizing is also not particularly limited, and a sizing method generally used in the art can be adopted and is not particularly limited.

Process III (mixing process)
As in step I, the mixing may be performed by a method capable of uniformly mixing the sized product prepared in step II with the D component and, if necessary, other components (for example, E component, C component, etc.). For example, it can be carried out by mixing using a mixer such as a rotary mixer or a fixed mixer. The mixing time is preferably about 4 to 6 minutes, more preferably about 3.5 to 4.5 minutes. When only a part of the C component is added in the step I, the rest (a part of the C component) is preferably added in the step III. The amount of the C component added in step III is preferably 50 to 67% by mass, more preferably 55 to 65% by mass, still more preferably 58 to 62, based on 100% by mass of the total amount of the C component contained in the tablet. The amount is mass%.

Process IV (compression molding (locking) process)
For locking, a locking method generally used in the art is adopted. Specifically, it can be performed by using a conventional locking machine such as a single-shot locking machine and a rotary locking machine.

Here, the tableting pressure and other tableting conditions are not limited as long as tablets having the effects of the present invention can be produced, but the following conditions can be mentioned.

The tableting pressure varies considerably depending on the size of the tablet (the amount of the active ingredient contained), but in the case of a tablet having a content of the active ingredient (famcyclovir) of 250 mg (hereinafter referred to as "250 mg tablet"), It is usually 430 to 710 kgf / cm ² , preferably 500 to 650 kgf / cm ² , more preferably 540 to 590 kgf / cm ² . On the other hand, when the content of the active ingredient is 500 mg tablets (hereinafter referred to as "500 mg tablets"), it is usually 800 to 1500 kgf / cm ² , preferably 900 to 1300 kgf / cm ² , and more preferably 1100-1150 kgf / cm. It is ^2.

Process V (coating process)
When producing a coated lock, a further coating step is performed.

For coating, a coating method commonly used in the art is adopted. Specific examples thereof include a pan coating method, a fluidized bed coating method, a breathable dry pan coating method, and the like, and coating can be performed using a coating device corresponding to these methods.

The coating is performed by coating the surface of the uncoated tablets produced in steps I to IV with a coating liquid in which the above-mentioned coating agent is mixed with a colorant, a flavoring agent, a sweetening agent, a flavoring agent, etc., if necessary. be able to.

3. 3. Characteristics of Tablets The shape of the tablet of the present invention is not particularly limited, but a known tablet shape is preferable, and examples thereof include circular tablets and oval tablets.

The content of component A in one tablet of the present invention is, for example, 245 to 255 mg (preferably 248 to 252 mg) in terms of famciclovir amount. In this case, the mass of the tablet is preferably 300-330 mg, more preferably 310-325 mg, even more preferably 315-325 mg, even more preferably 318 mg-322 mg, and the major axis of the tablet (the tablet is a circular tablet). The diameter) is preferably 8.5 to 9.5 mm, more preferably 8.8 to 9.3 mm, further preferably 9.0 to 9.2 mg, and the tablet thickness is preferably 4.7 to 5.7 mm, more preferably 5.0 to 5.4 mm. Yes, more preferably 5.1-5.3 mm.

The content of component A in one tablet of the present invention is, for example, 490 to 510 mg (preferably 495 to 505 mg, more preferably 498 to 502 mg) in terms of famciclovir amount. In this case, the mass of the tablet is preferably 600-660 mg, more preferably 620-650 mg, even more preferably 630-650 mg, even more preferably 635 mg-645 mg, and the shape of the tablet is preferably elliptical. It is a tablet, the major axis of the tablet is preferably 15-17 mm, more preferably 16-16.8 mm, even more preferably 16.2-16.6 mg, and the minor axis of the tablet is preferably 7.3-8.3 mm, more preferably 7.6-. It is 8.0 mm, more preferably 7.7 to 7.9 mg, and the tablet thickness is preferably 5.7 to 6.7 mm, more preferably 6.0 to 6.4 mm, still more preferably 6.1 to 6.3 mm.

The tablet of the present invention can be obtained while further suppressing tableting disorders. From this point of view, it is preferable that the tablet of the present invention has no scratches, cracks, cracks or other cracks in the appearance of the tablet by visual observation.

The tablets of the present invention have appropriate elution properties, preferably comparable to those of famciclovir tablets on the market. Specifically, when the tablet of the present invention is subjected to the dissolution test described in Test Example 1 described later, the dissolution rate after 30 minutes is, for example, 80% or more, preferably 85% or more, more preferably 85 to. It is 95%.

Hereinafter, the present invention will be described in detail based on examples, but the present invention is not limited to these examples.

Example 1. Production of Tablets 250 mg tablets and 500 mg tablets shown in Table 1 were produced through the following steps. Table 1 also shows the ingredients of famciclovir tablets (famciclovir (registered trademark) tablet 250 mg, manufactured by Asahi Kasei Pharma Co., Ltd.) that have already been put on the market (the ingredients indicated by ○ in Table 1 are blended). Indicates the components that are present.).

(1) Preparation of nuclear granules (granulation, drying, and sizing)
Famcyclovir 17500 g, lactose hydrate (DFE, trade name: PharmatoseR, 200M) 854 g, croscarmellose sodium (FMC International, trade name: Ac-Di-Sol) 896 g and hydroxypropyl cellulose Put 336 g (manufactured by Nippon Soda Co., Ltd., trade name: HPC-SL) into a high-speed stirring granulator (manufactured by Paulek Co., Ltd., FM-VG-100P: blade 110 rpm, cross screw 3585 r pm) and add 12000 g of purified water. It was added and granulated, and then dried in a fluidized bed drying device (manufactured by Freund Sangyo Co., Ltd., NFOD-120: air supply temperature 70 ° C.) until the water content of the granules became 1.0% or less. Next, the dried granules were sized with a screen type sizing machine (manufactured by Fuji Powder Co., Ltd., trade name: flash mill: screen size φ1.5 mm, rotation speed about 2000 Hz) to prepare nuclear granules.

(2) Preparation of uncoated tablets (mixing with extragranular additives, tableting)
Nuclear granules 39172 g prepared in (1) above, croscarmellose sodium 2688 g, light anhydrous silicic acid (manufactured by WKYF, trade name: Adsolider 101) 896 g, and magnesium stearate (Taipei Chemical Industry Co., Ltd.) 1344 g of (manufactured, vegetable / general product) was mixed with a V-type mixer (manufactured by Tokuju Kosakusho Co., Ltd., VM-200) for 5 minutes to obtain granules for tableting. Next, this was locked and molded with a locking machine (manufactured by Kikusui Seisakusho Co., Ltd., LIB20845SS1JY: rotation speed 25 rpm) at a locking load of 540 kgf to obtain an uncoated tablet.

(3) Preparation of coated lock (coating)
4.15 mass% hypromellose (Shin-Etsu Chemical Co., Ltd.) was applied to the uncoated tablet prepared in (2) above using a tablet coating device (HCFS-100 manufactured by Freund Sangyo Co., Ltd., air supply temperature 68 to 73 ° C, air volume 13 m ^{3 / min).} Co., Ltd., product name: TC-5R) aqueous solution 22934 g, titanium oxide (manufactured by Ishihara Sangyo Co., Ltd., product name: Typake_A-100) 224 g and polyethylene glycol (manufactured by Sanyo Kasei Co., Ltd., Macrogol 6000) 224 g The liquid was sprayed and coated, and polished with 4.5 g of carnauba wax (manufactured by Freund Sangyo Co., Ltd., trade name: Polyethylene Wax-105).

(4) Appearance and shape of the tablet When the appearance was visually observed, no cracks such as scratches, cracks and cracks were observed in the appearance of the tablet. Table 2 shows the external shape of the tablet.

Table 3 shows the appearance and shape of famciclovir tablets (250 mg tablets) that have already been put on the market.

As is clear from Tables 2 and 3, the 250 mg tablet obtained in Example 1 was smaller than the commercial product also containing 250 mg of the active ingredient.

Test example 1. Dissolution test Using a dissolution tester, for the 250 mg tablets obtained in the examples and the famciclovir tablets already on the market, using 900 mL of water, by the paddle method in accordance with the 17th revised Japanese Pharmacopoeia. The dissolution test was performed at 50 rpm. Accurately take 5 mL of the eluate at the specified time, centrifuge at 1000 rpm for 10 minutes, and use the obtained supernatant as the sample solution. For the sample solution, the elution concentration of famciclovir was measured by liquid chromatography. The test was conducted a total of 6 times.

The results are shown in Table 4. From the results, it was found that the obtained tablets showed an elution behavior similar to that of the products on the market.

Claims (11)

For 100% by mass of tablets
(A) 75 to 81% by mass of famciclovir or a salt thereof in terms of famciclovir amount, (B) 2 to 6% by mass of lactose hydrate,
(C) croscarmellose or a salt thereof in an amount of 8 to 15% by mass, and (D) a lubricant in an amount of 2 to 4% by mass.
Contains, tablets. The tablet according to claim 1, which contains 0.2 to 5% by mass of (E) a fluidizing agent with respect to 100% by mass of the tablet. The tablet according to claim 1 or 2, which contains 0.2 to 5% by mass of the (F) binder with respect to 100% by mass of the tablet. The tablet according to any one of claims 1 to 3 , which is a coated tablet. The tablet according to any one of claims 1 to 4 , wherein the content of the component (A) in one tablet is 245 to 255 mg. The tablet according to any one of claims 1 to 4 , wherein the content of the component (A) in one tablet is 490 to 510 mg. The tablet according to any one of claims 1 to 6 , wherein the content of the component (A) in one tablet is 77 to 79% by weight. The method for producing a tablet according to any one of claims 1 to 7 , which comprises a step of producing by using a granule compression method. The production method according to claim 8 , wherein the granulation method used in the granule compression method is a stirring granulation method. The production method according to claim 8 or 9 , wherein a part of the component (C) is added in a powder state after granulation. The production method according to claim 10 , wherein the amount of the component (C) added after granulation is 50 to 67% by mass with respect to 100% by mass of the total amount of the component (C) contained in the tablet.