JP2001316250A - Compressed solid preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a compressed solid preparation improved in preventing the trouble of the adhesion to a processing machine in a compression process and formulated with plural components causing the lowering of melting point. SOLUTION: This compressed solid preparation is improved in preventing the trouble of the adhesion to a processing machine by formulating plural components causing the lowering of melting point in a group division condition or by formulating plural components causing the lowering of melting point as pelletized grains at a processing temperature not fusing the components themselves.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a solid compressed preparation containing a plurality of components which cause a decrease in melting point, which is used in the field of medicine or food.

[0002]

2. Description of the Related Art A solid compressed preparation is produced by mixing an active ingredient with raw material ingredients such as other excipients and additives, granulating, drying and compressing such as tableting. .
However, depending on the properties of the components to be blended, the molding composition causes sticking of the punch at the time of compression molding, such as tableting, so that an identification code cannot be imprinted on the preparation, or a part of the preparation is missing, thereby causing molding problems. Sometimes. In particular, in the case of mass production, such a molding failure becomes a serious problem such as a machine stoppage. Even when the component itself does not have such a problem, the same problem may occur by blending with another component. Normal,
Such a molding obstacle is solved by a method such as adding a large amount of a lubricant such as magnesium stearate. However, since the lubricant itself may cause an interaction with other components, and the strength of the molded product may be impaired, it is desirable to avoid such a method as much as possible and to solve the problem.

[0003]

SUMMARY OF THE INVENTION It is an object of the present invention to improve the adhesion to a molding apparatus during the molding process as described above.
An object of the present invention is to provide a solid compressed preparation containing a plurality of components that cause a decrease in melting point, a method for producing the same, and a method for improving adhesion.

[0004]

DISCLOSURE OF THE INVENTION The present inventors have made intensive studies for the first time, paying particular attention to the fact that molding failure caused by blending a plurality of components is caused by a decrease in melting point between components. By mixing and compounding a plurality of components that cause a drop in each group, or by mixing a plurality of components that cause a decrease in melting point with granules granulated at a product temperature at which the plurality of components do not melt, the mixture is fed to a molding apparatus in a tableting process. Have been found to have improved tableting properties and good productivity, and have completed the present invention.

[0005] That is, the present invention provides (1) a solid compressed preparation in which a plurality of components that cause a decrease in melting point are separately compounded, and (2) a plurality of components that cause a decrease in melting point, at a temperature at which they do not melt. (3) After a plurality of components causing a decrease in melting point come into contact with each other,
The solid compressed preparation according to the above (1) or (2), wherein the melting point of one or more components having a lowered melting point is about 50 ° C. to about 90 ° C. after the melting point has been lowered, (4) a plurality of components that have a lowered melting point. The solid compressed preparation according to the above (1) or (2), which is a plurality of components that cause punch sticking in the tableting process as a result of causing a melting point drop, and (5) a plurality of components that cause a melting point drop,
The solid compressed preparation according to the above (1) or (2), which is chlorpheniramine maleate and dextromethorphan hydrobromide, and (6) chlorpheniramine maleate is d-
(5) the solid compressed preparation according to the above (5), which is chlorpheniramine maleate; (7) the solid compressed preparation according to the above (2), which comprises granulated granules at a product temperature of about 60 ° C. or lower.
(8) A plurality of components that cause a drop in melting point are grouped and compounded,
The method for producing a solid compressed preparation according to the above (1), in which both are mixed and molded, (9) the above-mentioned (2), in which a plurality of components that cause a decrease in melting point are granulated at a temperature at which they do not melt.
(10) a method for producing granules containing a plurality of components that cause a decrease in melting point, the method comprising granulating the components at a temperature at which they do not melt;
(11) a method for improving the adhesion of a solid compressed preparation containing the plurality of components to a molding apparatus during a tableting step, wherein each of the plurality of components causing a decrease in melting point is compounded in groups; and (12) A) providing a method for improving the adhesion of a solid compressed preparation containing the plurality of components to a molding apparatus during a tableting process, wherein the plurality of components causing a decrease in melting point are granulated at a temperature at which they do not melt. Is what you do.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION In the present specification, "melting point depression"
The term refers to a phenomenon in which a plurality of components come into contact with each other, and the melting point unique to each component drops after the contact. At this time,
Due to the contact of a plurality of components, the melting point of only one component may drop, the melting points of two or more components may each drop, or the melting points of two or more components may overlap and drop.
The “multiple components that cause a melting point drop” include two or more components (usually two components) that cause a melting point drop upon contact, and one component that causes a melting point drop and another component that causes the melting point drop (its melting point is (Which hardly drops) and is used in the production of various pharmaceuticals, quasi-drugs, foods, etc., which adhere to molding equipment (eg, punches, dies, etc.) in the tableting process as a result of the melting point drop. Such components are referred to. Adhesion to the molding apparatus in the tableting process is such that the melting point of one or two components that caused a decrease in melting point after contact is about 50 ° C. to about 90 ° C. (particularly, about 60 ° C. to about 80 ° C.).
° C). Here, the melting point after the melting point has fallen means a temperature at which the component starts to melt. Specific examples of the “plural components that cause a decrease in melting point” include, for example, chlorpheniramine maleate (eg, d-chlorpheniramine maleate, dl-chlorpheniramine maleate) and dextromethorphan hydrobromide A combination of acetaminophen and dextromethorphan hydrobromide, a combination of nicotinamide and d-α-tocopherol succinate, a combination of nicotinamide and fursultiamine hydrochloride, guaifenesin and odor Pharmaceutical ingredients consisting of a combination of dextromethorphan hydrohydride and a combination of guaifenesin and d-chlorpheniramine maleate are exemplified. Of these, the present invention is preferably used for a product of a combination of chlorpheniramine maleate and dextromethorphan hydrobromide, especially a product of a combination of d-chlorpheniramine maleate and dextromethorphan hydrobromide. Can be

[0007] The term "grouping and blending" refers to blending of a plurality of components, each of which causes a decrease in melting point, into separate groups in order to suppress contact with each other. "Granulation at the product temperature at which the multiple components that cause the melting point drop do not melt" means that once the multiple components that cause the melting point drop melt, they are then tableted at a product temperature (product temperature) lower than the melting point after the melting point drop. Since the adhesion to the molding apparatus is not improved even after the above, granulation is performed while maintaining the product temperature at which a plurality of components causing the melting point drop do not melt ("granulation" herein includes the drying step after granulation). This is to prevent the occurrence of adhesion to the molding device in the tableting process. In order to maintain such a product temperature, it is usually sufficient to blow air at a blowing temperature of about 20 to 30 ° C. higher than the product temperature in the granulation and drying steps. The term “temperature at which a plurality of components that cause a melting point drop do not melt” specifically means, for example, that a plurality of components that cause a melting point drop are chlorpheniramine maleate (eg,
d-chlorpheniramine maleate, dl-chlorpheniramine maleate) and dextromeltophan hydrobromide, a combination of acetaminophen and dextromethorphan hydrobromide, nicotinamide and succinic acid In the case of a combination with d-α-troferol, a combination of nicotinamide and fursultiamine hydrochloride, a combination of guaifenesin and dextromethorphan hydrobromide, or a combination of guaifenesin and d-chlorpheniramine maleate Is
It is about 60 ° C or less, preferably about 40-60 ° C, more preferably about 43-55 ° C. In the case of a combination of nicotinamide and d-α-tocopherol succinate, the temperature is about 65 ° C or less, preferably about 40 to 65 ° C, more preferably about 43 to 60 ° C.

[0008] The content of a plurality of components that cause a decrease in melting point is about 0.01% to about 70% by weight, preferably about 0.05% to about 50% by weight, based on the whole preparation. The solid compressed preparation of the present invention is preferably a solid preparation to be orally administered. In particular, the thickness is about 3 to 10 mm, and the diameter is about 4 to 20
Tablets having a size of about mm are preferred.

The preparation of the present invention may contain an active ingredient used in the production of other drugs, quasi-drugs, foods, etc., in addition to the plurality of components that cause a decrease in melting point. Such active ingredients include, for example, nourishing tonic health drugs, antipyretic analgesics and anti-inflammatory drugs, psychotropic drugs, anxiolytics, antidepressants, hypnotic sedatives, antispasmodics, gastrointestinal drugs, antacids, antitussive expectorants, Bronchodilators, oral and oral medicines, antihistamines, inotropics, arrhythmias, diuretics, antihypertensives, vasoconstrictors, coronary vasodilators, peripheral vasodilators, cholerics, antibiotics, bactericides, chemotherapy One or two or more components selected from an agent, an agent for diabetes, an agent for osteoporosis, a skeletal muscle relaxant, an analgesic, and a motion sickness drug are used.

[0010] Nourishing tonic health drugs include, for example, vitamin A
(Including vitamin A and its derivatives, abbreviated hereinafter), vitamin D, vitamin E (d-α-tocopherol acetate, etc.), vitamin B ₁ (dibenzoylthiamine, fursultiamine hydrochloride, etc.) , vitamin _{B 2} compounds (riboflavin butyrate, etc.), (such as pyridoxine hydrochloride) vitamin _{B 6,} vitamin C (ascorbic acid, sodium L- ascorbate), vitamin _{B 12} compound (acetate hydroxocobalamin etc.), vitamin K, vitamin Vitamins such as L, vitamin P (such as hesperidin),
Minerals such as calcium, magnesium, and iron, proteins, amino acids, oligosaccharides, and crude drugs. Antipyretic analgesics and anti-inflammatory drugs include, for example, aspirin, acetaminophen, etenzamide, ibuprofen, diphenhydramine hydrochloride, dl-chlorpheniramine maleate,
Dihydrocodeine phosphate, noscapine, methylephedrine hydrochloride, phenylpropanolamine hydrochloride, tranexamic acid, caffeine, caffeine anhydride, serrapeptase, lysozyme chloride, tolfenamic acid, mefenamic acid,
Diclofenac sodium, flufenamic acid, salicylamide, aminopyrine, ketoprofen, indomethacin, bucolome, pentazocine and the like. Psychotropic drugs include, for example, chlorpromazine, reserpine and the like. Examples of anxiolytics include chlordiazepoxide, diazepam and the like. Examples of antidepressants include imipramine, maprotiline,
Amphetamine and the like.

Examples of the sedative-hypnotic include estazolam, nitrazepam, diazepam, phenobarbital sodium and the like. Antispasmodics include, for example, scopolamine hydrobromide, diphenhydramine hydrochloride, papaverine hydrochloride and the like. As gastrointestinal drugs, for example,
Gastric digestive agents such as diastase, sugar-containing pepsin, funnel extract, lipase AP, calyx oil, and intestinal agents such as berberine chloride, resistant lactic acid bacteria, and bifidobacteria. As the antacid, for example, magnesium carbonate, sodium hydrogen carbonate, magnesium metasilicate aluminate,
Examples include synthetic hydrotalcite, precipitated calcium carbonate, and magnesium oxide. Examples of antitussive expectorants include cloperastine hydrochloride, dextromethorphan hydrobromide, theophylline, potassium guaiacol sulfonate, guaifenesin, dextromethorphane phenol phthalate, ambroxol hydrochloride and the like. Examples of the bronchodilator include dl-methylephedrine hydrochloride and the like. As a dental oral medicine,
Examples include oxytetracycline, triamcinolone acetonide, chlorhexidine hydrochloride, lidocaine and the like. As antihistamines, for example, diphenhydramine hydrochloride, promethazine, isotipendyl hydrochloride,
Chlorpheniramine d-maleate, chlorpheniramine male dl-maleate and the like can be mentioned. Examples of the cardiotonic agent include, for example, ethylephrine hydrochloride and the like. Examples of the agent for arrhythmia include procainamide hydrochloride, propranolol hydrochloride, pindolol and the like. Diuretics include, for example, isosorbide, furosemide and the like. Examples of the antihypertensive include delapril hydrochloride, captopril, hexamethonium bromide, hydralazine hydrochloride, labetalol hydrochloride, methyldopa and the like.

Examples of the vasoconstrictor include phenylephrine hydrochloride. Examples of the coronary vasodilator include carbochromene hydrochloride, molsidomine, verapamil hydrochloride and the like. Examples of the peripheral vasodilator include cinnarizine and the like. As a bolus,
For example, dehydrocholic acid, trepiptone and the like can be mentioned. Examples of the antibiotic include cephem, penem, and carbapenem antibiotics such as cephalexin, amoxicillin, pivmecillinam hydrochloride, and cefotiam hydrochloride. Examples of the bactericide include cetylpyridinium chloride and chlorhexidine hydrochloride. Chemotherapeutic agents include, for example, sulfamethizole, thiazosulfone and the like. Examples of the antidiabetic agent include tolbutamide, voglibose, and the like. Examples of the agent for osteoporosis include ipriflavone and the like. Skeletal muscle relaxants include, for example, methocarbamol and the like. Examples of the analgesic or motion sickness preventive / therapeutic include meclizine hydrochloride, dimenhydrinate and the like. The content of these active ingredients can be in a wide range depending on the kind of the active ingredients, for example, from about 0.001% by weight to the whole preparation.
It can be suitably selected from about 90% by weight, preferably from about 0.01% to about 50% by weight.

In the preparation of the present invention, excipients, binders, disintegrants, enteric polymers, water-insoluble polymers, lubricants, and the like, which are generally used in the preparation, are contained in amounts not to impair the effects of the present invention. It may contain a surfactant, a coloring agent, a flavoring agent, an adsorbent, a preservative, a wetting agent, an antistatic agent, a disintegration extender, a foaming agent, and the like. As an excipient, for example, lactose, starch,
Corn starch, crystalline cellulose (eg, Avicel PH1
01, Avicel PH-F20 (all trade names, manufactured by Asahi Kasei Kogyo Co., Ltd.), granulose sugar, mannitol, light anhydrous silicic acid (eg, Sylysia 320 (trade name,
Etc.), magnesium carbonate, calcium carbonate, refined sucrose, glucose, hydrous glucose and the like. Preferably, purified sucrose, glucose, hydrous glucose and the like are used.

Examples of the binder include sucrose, gelatin, gum arabic powder, methylcellulose, hydroxypropylcellulose (eg, HPC-L, etc.), hydroxypropylmethylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone, brulan, dextrin , Pregelatinized starch, gum arabic powder, gelatin and the like. Examples of the disintegrant include carboxymethylcellulose calcium, croscarmellose sodium (eg, Acdizol (trade name, manufactured by Asahi Kasei Kogyo Co., Ltd.)), cross-linked insoluble polyvinylpyrrolidone (eg, Kollidon CL (trade name, BASF) ), Low-substituted hydroxypropylcellulose, partially pregelatinized starch,
Crospovidone (ISP Inc., BASF), carmellose calcium (manufactured by Gotoku Pharmaceutical Co., Ltd.), sodium carboxymethyl starch (manufactured by Matsutani Chemical Co., Ltd.), corn starch and the like. Examples of the enteric polymer include hydroxypropylmethylcellulose phthalate, cellulose acetate phthalate, carboxymethylethylcellulose and the like. Examples of the water-insoluble polymer include aminoalkyl methacrylate copolymers (eg, Eudragit E, Eudragit RS, etc.) and methacrylic acid copolymers (eg, Eudragit L30-55, etc.).

As the lubricant, for example, polyethylene glycol, talc, stearic acid, sucrose fatty acid ester and the like can be mentioned. Examples of the sucrose fatty acid ester include sucrose fatty acid esters having a molecular weight of about 400 to 1300 (eg, sucrose laurate ester, sucrose myristic ester, sucrose palmitate ester, sucrose stearate ester, etc.). No. Sucrose laurate esters include sucrose monolaurate, sucrose dilaurate, sucrose trilaurate, and the like.Sucrose myristate esters include sucrose monomyristate,
Sucrose dimyristate, sucrose trimyristate, etc.
As sucrose palmitate, sucrose monopalmitate, sucrose dipalmitate, sucrose tripalmitate, etc., and as sucrose stearate, sucrose monostearate, sucrose distearate, sucrose tristearate, etc. No. As the surfactant, for example, anionic surfactants such as sodium alkyl sulfate, polyoxyethylene sorbitan fatty acid ester,
Non-ionic surfactants such as polyoxyethylene fatty acid esters and polyoxyethylene castor oil derivatives are exemplified. Examples of the coloring agent include tar dyes, caramel, red bengal, titanium oxide, riboflavin, green tea extract, copper chlorofin sodium, food dyes such as Food Yellow No. 5, Food Red No. 2, Food Blue No. 2, and food lakes. Dyes and the like. Examples of the flavoring agent include sweeteners (eg, artificial sweeteners such as sodium saccharin, dipotassium glycyrrhizinate, aspartame, stevia, thaumatin), flavors (eg, lemon, lemon lime, orange, 1-menthol, peppermint oil, peppermint) Micron X-8277-T, dry-coated matcha # 421, etc.), acidulants (eg, citric acid, tartaric acid, malic acid, etc.), green tea powder and the like. Examples of the adsorbent include special calcium silicate (Flolite). Examples of the antistatic agent include light silicic anhydride (aerosil). Examples of the foaming agent include baking soda.

The preparation of the present invention can be produced by compounding a plurality of components that cause a decrease in melting point into separate groups so as to suppress contact between the two components, and mixing and molding the two groups according to a conventional method. it can. To suppress contact between both components, usually
It is convenient to use the above-mentioned excipients and the like. For example, when there are a plurality of components a and b which cause a melting point drop, a raw material ingredient such as an excipient is added to the ingredient a and other active ingredients as needed, and the mixture is granulated by mixing Group A, b, and if necessary, a pharmaceutical ingredient such as an excipient is added to other pharmaceutical ingredients, and the resulting mixture is mixed with a granulated Group B, dried, and compression-molded (compressed). it can. Alternatively, the formulation of the present invention can be produced by molding a plurality of components that cause a decrease in melting point and granules at a temperature at which the plurality of components that cause a decrease in melting point do not melt according to a conventional method. For example, a plurality of ingredients that cause a decrease in melting point and, if necessary, raw material ingredients such as excipients are added to and mixed with other active ingredients, and granules are granulated at a temperature at which the ingredient that causes a decrease in melting point does not melt. It can be manufactured by drying at a product temperature at which a component causing a decrease in melting point does not melt, and compression molding (tableting). In the preparation of the present invention, the particle size of the particles before compression molding is about 10 to 2000 μm, preferably about 20 to 100 μm.
0 μm, more preferably about 100 to 500 μm.

The method of adding, mixing, and granulating the raw materials of the preparation to a plurality of components that cause a decrease in the melting point and, if necessary, other active ingredients is performed by a commonly used mixing method, granulation method, or the like. Specifically, Vertical Granulator VG10 (manufactured by Powrex), Universal Mixer (manufactured by Hata Iron Works), Rolling Fluidized Bed Granulator (manufactured by Powrex), Fluidized Bed Granulator (manufactured by Powrex), Tumbler Mixing and granulation can be performed using a mixer (manufactured by Showa Chemical Machinery Co., Ltd.) or the like. Drying may be performed by any method used for drying pharmaceuticals in general, such as vacuum drying, freeze drying, natural drying, and fluidized bed drying. For tableting, an apparatus used for molding a general tablet is used. For example, a single-shot tablet machine (manufactured by Kikusui Seisakusho), a rotary tablet machine (manufactured by Kikusui Seisakusho) and the like can be used. The molding pressure during tableting is, for example, about 1 to 1.
It is 50 kN, preferably about 5 to 30 kN.

[0018]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to Examples, Comparative Examples, and Test Examples, but these are not intended to limit the present invention.

Example 1 According to the formulation shown in Table 1, Group A containing d-chlorpheniramine maleate was added to a fluidized bed granulator (FD, manufactured by Powrex Co., Ltd.).
-3SN) to spray the HPC-L solution,
Granulation was carried out at 5 ° C. On the other hand, Group B containing dextromethorphan hydrobromide is also sprayed with the HPC-L solution,
Granulation was performed using a fluid bed granulator (FD-3SN, manufactured by Powrex) so that the product temperature would be 65 ° C. The two kinds of granules thus obtained, a disintegrant and a lubricant are mixed by a tumbler mixer (TM-15, manufactured by Showa Chemical Machinery Co., Ltd.) and uncoated with a rotary tableting machine (Kikusui Seisakusho, Collect 19K). Was manufactured.

Example 2 According to the formulation shown in Table 1, Group A containing d-chlorpheniramine maleate was added to a fluidized bed granulator (Fourec F.
D-3SN) and sprayed the HPC-L solution, and granulated so that the product temperature would be 50 ° C or lower. On the other hand, Group B containing dextromethorphan hydrobromide is also sprayed with HPC-L and granulated using a fluidized bed granulator (FD-3SN, manufactured by Powrex) so that the product temperature becomes 50 ° C. or lower. did. The two types of granules thus obtained, a disintegrant and a lubricant are mixed with a tumbler mixer (TM-15, manufactured by Showa Kagaku Kikai) and a rotary tableting machine (Collect 19K, manufactured by Kikusui Seisakusho).
To produce uncoated tablets.

[0021]

[Table 1]

Example 3 According to the formulation shown in Table 2, Group A was sprayed with an HPC-L solution using a fluidized bed granulator (FD-3SN, manufactured by Powrex) so that the product temperature would be 65 ° C. Granulated. On the other hand, a group B containing d-chlorpheniramine maleate and dextromethorphan hydrobromide is also sprayed with an HPC-L solution, and a fluidized bed granulator (manufactured by Powrex Co., Ltd.) so that the product temperature becomes 50 ° C. or lower. FD-3SN). Then, the obtained two kinds of granules, disintegrant and lubricant are mixed with a tumbler mixer (manufactured by Showa Kagaku Kikai Co., Ltd., TM-15 type) and uncoated tablets are formed with a rotary tableting machine (manufactured by Kikusui Seisakusho, collect 19K). Was manufactured.

Comparative Example 1 According to the formulation shown in Table 2, Group A was sprayed with an HPC-L solution using a fluidized bed granulator (FD-3SN, manufactured by Powrex) so that the product temperature would be 65 ° C. Granulated. On the other hand, group B containing d-chlorpheniramine maleate and dextromethorphan hydrobromide is also sprayed with an HPC-L solution, and a fluidized bed granulator (manufactured by Powrex Co., Ltd.) so that the product temperature becomes 65 ° C.
FD-3SN). Then, the obtained two kinds of granules, disintegrant and lubricant are mixed with a tumbler mixer (manufactured by Showa Kagaku Kikai Co., Ltd., TM-15 type) and uncoated tablets are formed with a rotary tableting machine (manufactured by Kikusui Seisakusho, collect 19K). Was manufactured.

[0024]

[Table 2]

Test Example 1 For Example 1, Example 2, Example 3, and Comparative Example 1, a rotary tableting machine (Collect 19, manufactured by Kikusui Seisakusho)
The tableting operation was performed in K). Table 3 shows the results.

[Table 3] As shown in Table 3, in each of the examples of the present invention, good tableting was performed. However, in the comparative example, punching occurred immediately after the start of tableting, so that tableting became impossible and the machine was stopped.

[0026]

According to the solid compressed preparation of the present invention, the identification code cannot be imprinted because a component does not adhere to the molding apparatus in the tableting step of its production, and a part of the preparation is missing.
Good tableting performance and productivity can be ensured without problems of molding failure such as machine stoppage due to adhesion to the molding device.

Claims (12)

[Claims] 1. A solid compressed preparation comprising a plurality of components which cause a decrease in melting point, each of which is divided into groups. 2. A solid compressed preparation comprising a plurality of components that cause a decrease in melting point, and granules formed at a temperature at which they do not melt. 3. The method according to claim 1, wherein the melting point of one or more of the components having a lowered melting point is from about 50 ° C. to about 90 ° C.
3. The solid compressed preparation according to item 1. 4. The solid compressed preparation according to claim 1, wherein the plurality of components that cause a decrease in melting point are a plurality of components that cause sticking of a punch in the tableting step as a result of causing a decrease in melting point. 5. The solid compressed preparation according to claim 1, wherein the plurality of components that cause a decrease in melting point are chlorpheniramine maleate and dextromethorphan hydrobromide. 6. The solid compressed preparation according to claim 5, wherein the chlorpheniramine maleate is d-chlorpheniramine maleate. 7. The solid compressed preparation according to claim 2, wherein granules granulated at a product temperature of about 60 ° C. or lower are blended. 8. The method for producing a solid compressed preparation according to claim 1, wherein a plurality of components that cause a decrease in the melting point are separately grouped, and both are mixed and molded. 9. The method for producing a solid compressed preparation according to claim 2, wherein a plurality of components causing a decrease in melting point are granulated at a temperature at which they do not melt. 10. A method for producing granules containing a plurality of components, wherein a plurality of components causing a decrease in melting point are granulated at a temperature at which they do not melt. 11. The method according to claim 11, wherein each of the plurality of components causing the melting point drop is:
A method for improving the adhesion of a solid compressed preparation containing a plurality of components to a molding apparatus during a tableting step, which is characterized by being divided into groups. 12. A method for adhering a plurality of components that cause a melting point drop to a molding apparatus during a tableting process of a solid compressed preparation containing the plurality of components, wherein the plurality of components are granulated at a temperature at which they do not melt. How to improve.