JP2013018759A - Method for producing solid preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for producing a solid preparation capable of producing easily a solid preparation involving a drug.SOLUTION: This method for producing a solid preparation includes: a step for forming a plurality of intermediate bodies including respectively an edible film having thermal deformation property and a pair of holding substrates installed so as to sandwich the edible film and having thermal deformation property; a step for forming a recessed part in the intermediate body by a heating pressurizing formation method; a step for obtaining a drug-filled body by filling a drug into the recessed part, after removing a holding substrate on the recessed part side of an intermediate body; a step in which a holding substrate on the recessed part side of another intermediate body is removed, and the exposed edible film is piled on the drug-filled body so that the recessed part is faced to the recessed part of the drug-filled body, and then each edible film is joined on the peripheral part of the recessed part, to thereby obtain a joined body; and a protection substrate removal step for obtaining the solid preparation by removing a residual protection substrate from the surface of the joined body.

Description

  The present invention relates to a method for producing a solid preparation.

  As oral administration agents containing drugs and taken from the mouth, for example, solid preparations such as tablets and capsules are known.

  Such an orally administered drug may have a reduced compliance due to various causes such as discomfort due to the bitterness or astringency of the drug, nausea or vomiting due to the drug, or rejection of the drug.

  In order to make swallowing relatively easy, various attempts have been made, for example, covering the drug with a material whose surface is dissolved by saliva in the oral cavity, or covering the drug with a material that absorbs water to form a gel. (For example, refer to Patent Document 1).

  However, it has been difficult to easily produce a solid preparation containing such a drug.

JP 11-116469 A

  An object of the present invention is to provide a method for producing a solid preparation capable of easily producing a solid preparation containing a drug.

Such an object is achieved by the present inventions (1) to (6) below.
(1) A first edible film having heat deformability, and a first holding base that is installed so as to sandwich the first edible film and has heat deformability. A first intermediate forming step of forming an intermediate of
A first recess forming step of forming a first recess in the first intermediate body by a heat and pressure molding method;
A second intermediate comprising a second edible film having heat deformability and a pair of second holding substrates having heat deformability installed so as to sandwich the second edible film. A second intermediate forming step of forming
A second recess forming step of forming a second recess in the second intermediate body by a heat and pressure molding method;
A drug filler forming step of obtaining a drug filler by filling the first recess with the drug after removing the first holding substrate on the first recess side of the first intermediate;
The second holding substrate on the second recess side of the second intermediate is removed, and the exposed second edible film is replaced with the second recess and the first of the drug filling body. The first edible film and the second edible film at the peripheral edge of the first concave portion and the second concave portion after being stacked on the drug filler so that the first concave portion faces the concave portion. And joining step of obtaining a joined body,
And a protective substrate removing step for removing the remaining first protective substrate and the second protective substrate from the surface of the joined body to obtain a solid formulation. .

  (2) The method for producing a solid preparation according to (1), wherein at least the drug filler forming step and the joining step are performed in an inert gas atmosphere.

  (3) The method for producing a solid preparation according to the above (1) or (2), wherein the first holding substrate and the second holding substrate are films composed of a thermoplastic resin.

  (4) The method for producing a solid preparation according to (3), wherein the thermoplastic resin is at least one selected from the group consisting of polyethylene, polypropylene, nylon, polyester, vinyl chloride, and vinylon.

  (5) The method for producing a solid preparation according to any one of (1) to (4) above, wherein the first edible film and the second edible film contain a thermoplastic polymer.

  (6) The thermoplastic polymer includes at least one selected from the group consisting of polyvinyl pyrrolidone, polyvinyl acetate, vinyl acetate / vinyl pyrrolidone copolymer, hydroxyalkyl cellulose, carboxyalkyl cellulose and starch (5 ). The manufacturing method of the solid formulation as described in.

  ADVANTAGE OF THE INVENTION According to this invention, the manufacturing method of the solid formulation which can manufacture easily the solid formulation which encloses a drug can be provided.

It is a front view which shows suitable embodiment of the solid formulation of this embodiment. It is a top view which shows suitable embodiment of the solid formulation of this embodiment. It is sectional drawing of the solid formulation in AA of FIG. It is sectional drawing which shows suitable embodiment of an edible film. It is process drawing which shows the manufacturing method of the solid formulation of this embodiment. It is process drawing which shows the manufacturing method of the solid formulation of this embodiment.

Hereinafter, the present invention will be described in detail based on preferred embodiments.
《Solid formulation》
Prior to the description of the method for producing the solid preparation of the present invention, the solid preparation produced by the method of the present invention will be described.

  FIG. 1 is a front view showing a preferred embodiment of the solid preparation of the present embodiment, FIG. 2 is a plan view showing a preferred embodiment of the solid preparation of the present embodiment, and FIG. 3 is AA of FIG. FIG. 4 is a cross-sectional view showing a preferred embodiment of an edible film.

  As shown in FIGS. 1 to 3, the solid preparation 1 includes a pair of edible films 10 (a first edible film 101 and a second edible film 102 described later) and a pair of edible films 10. It has the space part 20 formed by joining the peripheral parts, and the drug-containing part 30 accommodated in the space part 20.

  The edible film 10 is a film made of a material having heat deformability and dissolved by body fluid. The space part 20 mentioned later is formed by joining a pair of such edible films 10 in the peripheral part.

  In addition, the edible film 10 preferably contains a thermoplastic polymer. Thereby, it can thermoform easily in the manufacturing process mentioned later.

  The thermoplastic polymer is not particularly limited, and includes at least one selected from the group consisting of polyvinyl pyrrolidone, polyvinyl acetate, vinyl acetate / vinyl pyrrolidone copolymer, hydroxyalkyl cellulose, carboxyalkyl cellulose and starch. It is preferable. Thereby, it can thermoform more easily in the manufacturing process mentioned later.

  In the present embodiment, the edible film 10 includes an adhesion preventing layer 11, a gel forming layer 12, and an adhesive layer 13, as shown in FIG. In addition, the thermoplastic polymer mentioned above should just be contained in one of these layers.

  The adhesion preventing layer 11 is laminated on the main surface opposite to the space 20 and is provided as a surface layer located on the surface of the edible film 10.

  Moreover, the adhesion prevention layer 11 has a function which melt | dissolves rapidly with water | moisture contents, such as saliva, in the oral cavity, and prevents that the solid formulation 1 (edible film 10) adheres to the inner wall in an oral cavity.

  By providing such an adhesion preventing layer 11, when the solid preparation 1 is administered into the oral cavity, the surface portion of the adhesion preventing layer 11 quickly dissolves in saliva. A liquid film is quickly formed between the inner wall and the inner wall, so that the solid preparation 1 becomes slippery with respect to the inner wall. For this reason, the solid preparation 1 is prevented from coming into contact with the inner wall and hardly adheres to the inner wall of the oral cavity. Moreover, even if it is a case where a part of solid formulation 1 adheres to an inner wall, the solid formulation 1 will become easy to peel from an inner wall. Thereby, while being able to prevent the solid formulation 1 adhering to an inner wall and causing discomfort, it becomes easy to swallow the solid formulation 1. In addition, the drug can be reliably transported to a target site in the body. Moreover, it becomes possible to apply the chemical | medical agent which exhibits unpleasant taste (for example, bitterness, astringency, a feeling of numbness), smell, etc. to the solid formulation 1.

  The material constituting the adhesion preventing layer 11 (adhesion preventing agent) is not particularly limited. For example, hydroxyalkyl cellulose, polyethylene glycol, polypropylene glycol, polyvinyl alcohol, polyoxyl stearate, polyoxyethylene polyoxypropylene glycol, polyoxy Water-soluble polymer materials such as ethylene hydrogenated castor oil, gum arabic and gelatin, erythritol, sorbitol, xylitol, mannitol, inositol, maltitol, lactitol, glucose, xylose, mannose, fructose, galactose, sucrose, fructose, sucrose, etc. , Propylene glycol, glycerin, and the like. Among these, one or a combination of two or more can be used. Examples of the hydroxyalkyl cellulose include hydroxypropyl cellulose, hydroxypropyl methylcellulose, methylcellulose and the like.

  Among the above-mentioned, the adhesion preventing layer 11 preferably contains a water-soluble polymer material as an adhesion preventing agent. The water-soluble polymer material can be suitably dissolved in moisture and has a molecular chain with an appropriate length. For this reason, the water-soluble polymer material can appropriately entangle the molecular chains of a plurality of water-soluble polymers constituting the water-soluble polymer material. Can be unevenly distributed. For this reason, it is prevented that the solid formulation 1 adheres to the inner wall of an oral cavity reliably over a longer period. In addition, the water-soluble polymer material as described above can also function as a base of the adhesion preventing layer 11, can facilitate the production of the edible film 10, and the produced edible film 10. The durability at the time of storage can be made particularly excellent. In particular, among the above-mentioned water-soluble polymer materials, when at least one selected from hydroxypropylmethylcellulose, polyethylene glycol and polyvinyl alcohol is used, the above-described effects can be obtained more remarkably.

  Moreover, the adhesion preventing layer 11 may contain components other than those described above. For example, the adhesion preventing layer 11 may include a plasticizer, a masking agent, a preservative, a colorant, and the like.

  Examples of the plasticizer include glycerin, polyethylene glycol, triethyl citrate, propylene glycol, polyoxyethylene / polyoxypropylene glycol, triacetylene, polysorbate 80, and the like. Examples of masking agents include sweeteners such as saccharin, glycyrrhizic acid, sucrose, fructose, mannitol, acesulfame potassium, saccharin sodium, stevia extract, aspartame, sucralose, neotame, thaumatin; and sour tastes such as citric acid, tartaric acid, and fumaric acid. The charge; etc. are mentioned. Examples of the preservative include benzalkonium chloride and paraben. Examples of the colorant include titanium oxide, iron sesquioxide, and food red.

  The gel forming layer 12 is provided between the adhesion preventing layer 11 and an adhesive layer 13 described later, and is a layer that can swell to form a gel by absorbing moisture.

  The gel-forming layer 12 quickly absorbs moisture in saliva in the oral cavity to form a gel, so that in the oral cavity, the solid preparation 1 is quickly given flexibility and is easy to swallow. Become.

  The gel forming layer 12 includes a gel forming agent that swells by absorbing moisture to form a gel. By including such a gel-forming agent, the gel-forming layer 12 can easily and quickly absorb the surrounding water and form a gel.

  The gel forming agent is not particularly limited, and examples thereof include carboxyvinyl polymer, starch and derivatives thereof, agar, alginic acid, arabinogalactan, galactomannan, cellulose and derivatives thereof, carrageen, dextran, tragacanth, gelatin, pectin, and hyaluron. Acid, gellan gum, collagen, casein, xanthan gum and the like can be mentioned, and one or more of these can be used in combination.

  The gel forming agent may be cross-linked by ionic bond or covalent bond or may not be cross-linked.

  Further, the gel forming layer 12 may include a water absorption accelerator that promotes water absorption of the gel forming layer 12. When the gel forming layer 12 contains a water absorption accelerator, the water absorption speed of the gel forming layer 12 in the oral cavity is sufficiently high. For this reason, the swallowability of the solid preparation 1 is particularly excellent.

  As the water absorption accelerator, for example, a component having a relatively high solubility in water can be used. Since a component having a relatively high solubility in water dissolves in water, water can be transported into the gel forming layer 12, and as a result, the gel forming layer 12 can quickly absorb moisture.

  The water absorption promoter is not particularly limited. For example, glycols such as propylene glycol, polyethylene glycol, polypropylene glycol, polyoxyl stearate, polyoxyethylene polyoxypropylene glycol, polyoxyethylene hydrogenated castor oil, glycerin, erythritol, sorbitol , Sugars such as xylitol, mannitol, inositol, maltitol, lactitol, glucose, xylose, mannose, fructose, galactose, sucrose, fructose, sucrose, etc., among which one or more can be used in combination .

  Moreover, the gel forming layer 12 may contain components other than those described above. For example, it may contain a plasticizer, a masking agent, a preservative, a colorant and the like described in the description of the adhesion preventing layer 11.

  The adhesive layer 13 is a layer having a function of adhering the peripheral portions of the pair of edible films 10 and is provided on the space 20 side.

  Although it does not specifically limit as a material which comprises the contact bonding layer 13, It is preferable to be comprised with at least 1 sort (s) of material selected from the group which consists of polyvinylpyrrolidone, polyvinyl acetate, and a vinyl acetate vinylpyrrolidone copolymer. . Thereby, it becomes possible to join the edible films 10 easily with heat.

  Moreover, the adhesive layer 13 may contain components other than those described above. For example, it may contain a plasticizer, a masking agent, a preservative, a colorant and the like described in the description of the adhesion preventing layer 11.

  The space portion 20 is a space formed by joining the peripheral portions of the pair of edible films 10 described above, and has a function of accommodating a drug-containing portion 30 described later.

  The shape of the space 20 is preferably substantially spherical as shown in FIGS. Thereby, when taking the solid preparation 1, the contact area with the oral cavity, the esophagus, etc. can be made comparatively small, and it becomes possible to swallow easily.

  The space 20 is preferably filled with an inert gas. Thereby, the stability of the drug in the drug containing part 30 can be improved.

  Note that in this specification, an inert gas refers to a gas that hardly causes a chemical reaction, and is a concept that includes, for example, a rare gas group element such as helium, neon, or argon, nitrogen, and the like.

  The oxygen concentration in the space 20 is preferably 1% or less, more preferably 0.1% or less, and particularly preferably 0.01% or less.

The drug containing part 30 is a part containing the drug to be administered.
The volume ratio of the drug-containing part 30 to the volume inside the space part 20 is preferably 0.5 to 0.95, and more preferably 0.6 to 0.9. And it is preferable to adjust the volume ratio of the drug containing part 30 to the volume inside the space part 20 so that the specific gravity of the solid preparation is less than 1 g / cm ³ (preferably less than 0.95 g / cm ³ ). As a result, the solid preparation 1 can float in the gastric juice and stay in the stomach without sinking in the gastric juice as in the conventional solid preparation in the stomach after taking. As a result, a necessary amount of drug can be reliably released into the stomach.

  Examples of the drug contained in the drug-containing part 30 include drugs that act on the central nervous system such as amobarbital, estazolam, triazolam, nitrazepam, pentobarbital, and other hypnotics, amitriptine hydrochloride, imipramine hydrochloride, oxazolam, chlordiazepoxide, chlorpromazine, Psychotropic drugs such as diazepam, sulpiride, haloperidol, antiparkinson drugs such as trihexyphenidyl, levodopa, analgesics such as aspirin, isopropylantipyrine, indomethacin, diclofenac sodium, mefenamic acid, streptokinase, streptodornase, serrapeptase, pronase And central nervous system metabolism stimulators such as anti-inflammatory drugs, ATP and vinpocetine, and drugs acting on the respiratory tract, such as carbocysteine and promhexine hydrochloride Anti-asthma drugs such as glaze, azelastine hydrochloride, oxatomide, theophylline, terbutaline sulfate, tranilast, procaterol hydrochloride, ketotifen fumarate, and other drugs acting on the circulatory system include cardiotonic drugs such as aminophylline, digitoxin, digoxin, adimarin, disopyramide Antiarrhythmic drugs such as procainamide hydrochloride, mexiletine hydrochloride, amyl nitrite, alprenolol hydrochloride, isosorbide nitrate, nicorandil nitrate, oxyfedrine, dipyridamole, dilazep hydrochloride, diltiazem hydrochloride, nitroglycerin, nifedipine, verapamil hydrochloride, etc. Peripheral vasodilators such as psychiatric drugs, kallidinogenase, atenolol, captopril, clonidine hydrochloride, metoprolol tartrate, spironolactone, triamterene, trichlormethiazide, nicardi , Hydralazine hydrochloride, hydrochlorothiazide, prazosin hydrochloride, furosemide, propranolol hydrochloride, enalapril maleate, methyldopa, labetalol hydrochloride, reserpine and other antihypertensive drugs, clofibrate, dextran sulfate, anti-arteriosclerotic drugs such as nicomol, niceritrol, blood and Hematopoietic agents, hemostatic agents such as sodium carbazochrome sulfonate and tranexamic acid, antithrombotic agents such as ticlopidine hydrochloride and warfarin potassium, anti-anemic agents such as iron sulfate, drugs that act on the digestive system, azulene, aldioxa, Anti-ulcer drugs such as cimetidine, ranitidine hydrochloride, famotidine, teprenone, rebamipide, antiemetics such as domperidone and metoclopramide, suppositories such as sennoside, digestive enzyme preparations, glycyrrhizin, liver extract preparations, etc. Drugs for liver diseases, drugs acting on metabolic diseases, antidiabetic drugs such as glibenclamide, chlorpropamide, tolbutamide, gout drugs such as allopurinol and colchicine, drugs for ophthalmology, acetazolamide, drugs for otolaryngology Anti-vertigo drugs such as diphenidol hydrochloride and betahistine mesylate, chemotherapeutic drugs and antibiotics such as isoniazid, ethambutol hydrochloride, ofloxacin, erythromycin stearate, cefaclor, norfloxacin, fosfomycin calcium, minocycline hydrochloride, rifampicin, rokitamycin Drugs such as cyclophosphamide, tegafur, etc .; immunosuppressive drugs such as azathioprine, hormones and endocrine therapeutic agents such as progesterone, salivary gland hormone, thiamazole, Donisolone, betamethasone, liothyronine, levothyroxine, and other biologically active substances (ortachoids), antihistamines such as diphenhydramine hydrochloride, clemastine fumarate, chlorpheniramine maleate, alphacalcidol, cobamide, tocopherol nicotinate, mecoparamine These can be used, and one or more of these can be used in combination depending on the purpose of treatment / prevention.

  Moreover, the drug containing part 30 may contain a base. Examples of the base include cellulose such as crystalline cellulose, carboxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, methyl cellulose, ethyl cellulose, cellulose acetate, cellulose acetate phthalate, hydroxypropyl methyl cellulose phthalate, hydroxypropyl methyl cellulose acetate succinate, carboxymethyl ethyl cellulose, and the like. And derivatives thereof or pharmaceutically acceptable salts thereof (for example, sodium salts); starches such as α-starch, oxidized starch, sodium carboxymethyl starch, hydroxypropyl starch, dextrin, dextran, and derivatives thereof; dimethyl methacrylate Aminoethyl-methacrylic acid copolymer, methacrylic acid Ethyl laurate copolymer, methacrylic acid / methyl methacrylate copolymer, ethyl methacrylate / methacrylated trimethylammonium copolymer, dimethylaminoethyl methacrylate / methacrylated methyl copolymer, methacrylate / ethyl acrylate Acrylic acid derivatives such as copolymers; shellac; polyvinyl acetal diethylaminoacetate; polyvinyl acetate; polyvinyl alcohol; polyvinyl pyrrolidone; vinyl acetate-vinyl pyrrolidone copolymers; natural rubbers such as gum arabic and tragacanth; polyglucosamines such as chitin and chitosan Proteins such as gelatin, casein and soybean protein; calcium monohydrogen phosphate; calcium carbonate; talc; stearate; magnesium aluminate metasilicate Magnesium silicate, silicic anhydride, and the like, and depending on the purpose of addition, one or more of these can be selected and used.

  Further, the drug-containing unit 30 may contain components other than those described above. For example, it may contain a plasticizer, a masking agent, a preservative, a colorant and the like described in the description of the adhesion preventing layer 11.

<< Method for producing solid preparation >>
Next, the manufacturing method of the solid formulation of this invention is demonstrated in detail.
5 and 6 are process diagrams showing the method for producing the solid preparation of the present embodiment.

  The method for producing a solid preparation of the present embodiment includes a first edible film 101 having heat deformability and a pair of first edible films that are installed so as to sandwich the first edible film 101 and have heat deformability. A first intermediate forming step of forming a first intermediate 121 provided with the holding substrate 111, and a first recess 131 formed in the first intermediate 121 by a heat and pressure molding method. 1 dent forming step, a second edible film 102 having heat deformability, and a pair of second holding base materials 112 which are installed so as to sandwich the second edible film 102 and have heat deformability. And a second intermediate forming step for forming a second concave portion 132 in the second intermediate 122 by a heat and pressure molding method. And the first intermediate body 121 on the first recess 131 side. After removing the holding substrate 111, a drug filling body forming step of filling the drug (drug-containing section) 30 in the first recess 131 to obtain the drug filler 140, and the second recess of the second intermediate 122 The second holding substrate 112 on the 132 side is removed, and the exposed second edible film 102 is placed so that the second recess 132 and the first recess 131 of the drug filling body 140 face each other. After overlapping the drug filler 140, the first edible film 101 and the second edible film 102 are joined at the peripheral edge portions of the first recess 131 and the second recess 132, and the joined body 150 is joined. And a protective base material removing step for removing the remaining first protective base material 111 and the second protective base material 112 from the surface of the joined body 150 to obtain the solid preparation 1.

  By having such a process, the solid preparation 1 containing the drug can be easily produced. In addition, since the manufacturing method is simple, the occurrence of defective products can be suppressed, and the yield can be increased.

Hereinafter, each step will be described.
[First Intermediate Forming Step]
In this step, the first intermediate 121 as shown in FIG. 5A, that is, the first edible film 101 having heat deformability, and the first edible film are sandwiched. Then, the first intermediate body 121 including a pair of first holding base materials 111 having heat deformability is formed.

  Since the 1st edible film 101 is the structure similar to the edible film 10 mentioned above, the description is abbreviate | omitted.

  The first protective substrate 111 has a function of protecting the first edible film 101 and is a film having heat deformability.

  Such a first protective substrate 111 is preferably composed mainly of a thermoplastic resin. By comprising a thermoplastic resin, the thermoformability can be made higher.

  The thermoplastic resin is not particularly limited, but is preferably at least one selected from the group consisting of polyethylene, polypropylene, nylon, polyester, vinyl chloride, and vinylon. Thereby, thermoformability can be made still higher.

  Such a first intermediate 121 is formed by, for example, applying and drying a material constituting each layer of the edible film as described above on one first protective substrate 111 to thereby provide a first edible property. The film 101 can be formed and then bonded to the other first protective substrate 111.

[First recess forming step]
Next, as shown in FIGS. 5A and 5B, the first recess 131 is heated and applied to the first intermediate body 121 obtained as described above using the thermoformer 200. Pressure forming.

  The formed first recess 131 is used to form the space 20 described above, and the drug-containing portion 30 is accommodated in the space 20.

[Second Intermediate Forming Step]
On the other hand, in the same manner as the first intermediate formation step, the second edible film 102 having heat deformability and the pair of heat deformable films 102 are installed so as to sandwich the second edible film 102. A second intermediate body 122 including the second holding substrate 112 is formed.

[Second recess forming step]
Next, in the same manner as the first recess forming step described above, the first recess 132 is formed by heating and pressurizing the first intermediate 122 obtained as described above.

[Drug filling process]
Next, as shown in FIG. 6C, the first holding substrate 111 on the first recess 131 side of the first intermediate body 121 is removed. Thereby, the 1st edible film 101 is exposed.

  Next, as shown in FIG. 6C, the drug (drug-containing part) 30 is filled in the first recess 131 of the exposed first edible film 101. Thereby, the drug filling body 140 is obtained.

  This step is preferably performed in an inert gas atmosphere as described above. Thereby, the stability of the drug can be improved.

[Jointing process]
Next, the second holding substrate 112 on the second recess 132 side of the second intermediate body 122 is removed, and the second edible film 102 is exposed.

  Next, the exposed second edible film 102 is overlaid on the drug filler 140 such that the second recess 132 and the first recess 131 of the drug filler 140 face each other.

  And as shown in FIG.6 (c), (d), in the peripheral part of the 1st recessed part 131 and the 2nd recessed part 132, using the heat sealer 300, the 1st edible film 101 and the 2nd The edible film 102 is bonded to obtain a bonded body 150.

  This step is preferably performed in an inert gas atmosphere as in the drug filler forming step. Thereby, the stability of the drug can be improved.

[Protective substrate removal step]
Thereafter, the remaining first protective base material 111 and second protective base material 112 are removed from the joined body 150 to obtain a solid preparation 1 as shown in FIG.

  As mentioned above, although this invention was demonstrated about embodiment of illustration, this invention is not limited to this.

  For example, the edible film constituting the solid preparation may have an arbitrary layer other than the adhesion preventing layer, the gel forming layer, and the adhesive layer.

  Specific examples of the optional layer include a disintegration control layer made of a material containing a gastric material that dissolves when in contact with gastric juice.

  The gastric soluble material is not particularly limited, and for example, a material that dissolves under acidic conditions and hardly dissolves under neutral and alkaline conditions can be used. Specifically, as the gastric material, various inorganic compounds such as calcium carbonate and sodium hydrogen carbonate, various gastric polymers and the like can be used. These compounds can be used alone or in combination of two or more.

  Gastric soluble polymers include gastric soluble polyvinyl derivatives such as polyvinyl amino acetal and polyvinyl acetal diethyl amino acetate, methyl (meth) acrylate-butyl (meth) acrylate-dimethyl (meth) acrylate, aminoalkyl Examples include gastric soluble acrylic acid copolymers such as (meth) acrylate copolymers.

  Moreover, for example, the edible film constituting the solid preparation of the present invention may be a single layer film such as an adhesion preventing layer, a gel-forming layer, a disintegration control layer, or a laminated film thereof.

  Examples of the laminated film include an adhesion prevention layer / gel formation layer, an adhesion prevention layer / disintegration control layer, an adhesion prevention layer / adhesion layer, a gel formation layer / adhesion layer, a collapse control layer / adhesion layer, and a gel formation layer / disintegration. Control layer, disintegration control layer / gel formation layer, gel formation layer / disintegration control layer / adhesion layer, adhesion prevention layer / gel formation layer / disintegration control layer, adhesion prevention layer / disintegration control layer / gel formation layer, adhesion prevention layer / Examples thereof include a gel-forming layer / disintegration control layer / adhesion layer, an adhesion prevention layer / disintegration control layer / gel-formation layer / adhesion layer and the like, and a film having an arbitrary layer between these layers.

  In the above-described embodiment, the space portion has a substantially spherical shape. However, the present invention is not limited to this.

  Moreover, the manufacturing method of the solid formulation of this invention is not limited to embodiment mentioned above, For example, arbitrary processes may be added.

DESCRIPTION OF SYMBOLS 1 ... Solid preparation 10 ... Edible film 11 ... Adhesion prevention layer 12 ... Gel formation layer 13 ... Adhesive layer 20 ... Space part 30 ... Drug containing part 101 ... 1st edible film 102 ... 2nd edible film 111 ... 1st holding substrate 112 ... 2nd holding substrate 121 ... 1st intermediate body 122 ... 1st 2 intermediate body 131 ... 1st recessed part 132 ... 2nd recessed part 140 ... drug filling body 150 ... joined body 200 ... thermoforming device 300 ... heat sealer

Claims (6)

A first intermediate comprising a first edible film having heat deformability and a pair of first holding substrates having heat deformability installed so as to sandwich the first edible film. A first intermediate forming step of forming
A first recess forming step of forming a first recess in the first intermediate body by a heat and pressure molding method;
A second intermediate comprising a second edible film having heat deformability and a pair of second holding substrates having heat deformability installed so as to sandwich the second edible film. A second intermediate forming step of forming
A second recess forming step of forming a second recess in the second intermediate body by a heat and pressure molding method;
A drug filler forming step of obtaining a drug filler by filling the first recess with the drug after removing the first holding substrate on the first recess side of the first intermediate;
The second holding substrate on the second recess side of the second intermediate is removed, and the exposed second edible film is replaced with the second recess and the first of the drug filling body. The first edible film and the second edible film at the peripheral edge of the first concave portion and the second concave portion after being stacked on the drug filler so that the first concave portion faces the concave portion. And joining step of obtaining a joined body,
And a protective substrate removing step for removing the remaining first protective substrate and the second protective substrate from the surface of the joined body to obtain a solid formulation. .   The method for producing a solid preparation according to claim 1, wherein at least the drug filler forming step and the joining step are performed in an inert gas atmosphere.   The method for producing a solid preparation according to claim 1 or 2, wherein the first holding substrate and the second holding substrate are films made of a thermoplastic resin.   The method for producing a solid preparation according to claim 3, wherein the thermoplastic resin is at least one selected from the group consisting of polyethylene, polypropylene, nylon, polyester, vinyl chloride, and vinylon.   The method for producing a solid preparation according to any one of claims 1 to 4, wherein the first edible film and the second edible film contain a thermoplastic polymer.   The said thermoplastic polymer contains at least 1 sort (s) selected from the group which consists of polyvinylpyrrolidone, polyvinyl acetate, a vinyl acetate vinylpyrrolidone copolymer, a hydroxyalkyl cellulose, a carboxyalkyl cellulose, and starch. A method for producing a solid preparation.

Images