JP5694773B2 - COMPRESSION MOLDED PREPARATION AND METHOD - Google Patents
COMPRESSION MOLDED PREPARATION AND METHOD Download PDFInfo
- Publication number
- JP5694773B2 JP5694773B2 JP2010531841A JP2010531841A JP5694773B2 JP 5694773 B2 JP5694773 B2 JP 5694773B2 JP 2010531841 A JP2010531841 A JP 2010531841A JP 2010531841 A JP2010531841 A JP 2010531841A JP 5694773 B2 JP5694773 B2 JP 5694773B2
- Authority
- JP
- Japan
- Prior art keywords
- polyvinyl alcohol
- compression
- starch
- orally disintegrating
- preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 238000002360 preparation method Methods 0.000 title claims description 50
- 238000000034 method Methods 0.000 title claims description 29
- 238000007906 compression Methods 0.000 title description 5
- 230000006835 compression Effects 0.000 title description 5
- 238000004519 manufacturing process Methods 0.000 claims description 43
- 229920002472 Starch Polymers 0.000 claims description 32
- 235000019698 starch Nutrition 0.000 claims description 32
- 239000006191 orally-disintegrating tablet Substances 0.000 claims description 29
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 25
- 238000000748 compression moulding Methods 0.000 claims description 24
- 239000008107 starch Substances 0.000 claims description 24
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 22
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 21
- 235000010355 mannitol Nutrition 0.000 claims description 20
- 229930195725 Mannitol Natural products 0.000 claims description 19
- 239000000594 mannitol Substances 0.000 claims description 19
- 150000005846 sugar alcohols Chemical class 0.000 claims description 19
- 239000008187 granular material Substances 0.000 claims description 15
- 229920002554 vinyl polymer Polymers 0.000 claims description 15
- 229920000642 polymer Polymers 0.000 claims description 13
- 239000002202 Polyethylene glycol Substances 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 12
- 229920001223 polyethylene glycol Polymers 0.000 claims description 12
- 229920005596 polymer binder Polymers 0.000 claims description 12
- 239000002491 polymer binding agent Substances 0.000 claims description 12
- 229920000578 graft copolymer Polymers 0.000 claims description 11
- 150000001875 compounds Chemical class 0.000 claims description 10
- 229920000881 Modified starch Polymers 0.000 claims description 8
- 239000004480 active ingredient Substances 0.000 claims description 8
- 229920006243 acrylic copolymer Polymers 0.000 claims description 7
- 238000009472 formulation Methods 0.000 claims description 5
- 239000007864 aqueous solution Substances 0.000 claims description 4
- 230000000975 bioactive effect Effects 0.000 claims description 2
- 239000003826 tablet Substances 0.000 description 38
- 239000003795 chemical substances by application Substances 0.000 description 18
- -1 mannitol Chemical class 0.000 description 16
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 210000000214 mouth Anatomy 0.000 description 13
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- 238000005469 granulation Methods 0.000 description 8
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- 239000013543 active substance Substances 0.000 description 5
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- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 229920002678 cellulose Polymers 0.000 description 4
- 239000001913 cellulose Substances 0.000 description 4
- 239000011248 coating agent Substances 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
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- 239000004375 Dextrin Substances 0.000 description 3
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 3
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 235000019425 dextrin Nutrition 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 3
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 3
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- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
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- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 2
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 2
- BGRJTUBHPOOWDU-NSHDSACASA-N (S)-(-)-sulpiride Chemical compound CCN1CCC[C@H]1CNC(=O)C1=CC(S(N)(=O)=O)=CC=C1OC BGRJTUBHPOOWDU-NSHDSACASA-N 0.000 description 2
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- 102000013142 Amylases Human genes 0.000 description 2
- 108010065511 Amylases Proteins 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 108010011485 Aspartame Proteins 0.000 description 2
- SOGAXMICEFXMKE-UHFFFAOYSA-N Butylmethacrylate Chemical compound CCCCOC(=O)C(C)=C SOGAXMICEFXMKE-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical class [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 2
- CXOFVDLJLONNDW-UHFFFAOYSA-N Phenytoin Chemical compound N1C(=O)NC(=O)C1(C=1C=CC=CC=1)C1=CC=CC=C1 CXOFVDLJLONNDW-UHFFFAOYSA-N 0.000 description 2
- 239000004373 Pullulan Substances 0.000 description 2
- 229920001218 Pullulan Polymers 0.000 description 2
- IKMPWMZBZSAONZ-UHFFFAOYSA-N Quazepam Chemical compound FC1=CC=CC=C1C1=NCC(=S)N(CC(F)(F)F)C2=CC=C(Cl)C=C12 IKMPWMZBZSAONZ-UHFFFAOYSA-N 0.000 description 2
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 2
- 238000005299 abrasion Methods 0.000 description 2
- VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 229920003144 amino alkyl methacrylate copolymer Polymers 0.000 description 2
- VIROVYVQCGLCII-UHFFFAOYSA-N amobarbital Chemical compound CC(C)CCC1(CC)C(=O)NC(=O)NC1=O VIROVYVQCGLCII-UHFFFAOYSA-N 0.000 description 2
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- 239000001961 anticonvulsive agent Substances 0.000 description 2
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- CUFNKYGDVFVPHO-UHFFFAOYSA-N azulene Chemical compound C1=CC=CC2=CC=CC2=C1 CUFNKYGDVFVPHO-UHFFFAOYSA-N 0.000 description 2
- 229940124630 bronchodilator Drugs 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
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- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 2
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 2
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- 229940011671 vitamin b6 Drugs 0.000 description 1
- 229960001729 voglibose Drugs 0.000 description 1
- 229920003176 water-insoluble polymer Polymers 0.000 description 1
- 239000013585 weight reducing agent Substances 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- 229950004227 zaltoprofen Drugs 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
- FYGDTMLNYKFZSV-BYLHFPJWSA-N β-1,4-galactotrioside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@H](CO)O[C@@H](O[C@@H]2[C@@H](O[C@@H](O)[C@H](O)[C@H]2O)CO)[C@H](O)[C@H]1O FYGDTMLNYKFZSV-BYLHFPJWSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Preparation (AREA)
Description
本発明は、口腔内崩壊錠等の圧縮成型製剤およびその製造方法に関し、さらに詳細には、生産、輸送時に損耗がない程度の硬度を有しながら、口腔内においては優れた崩壊性を有し、更に既存設備での製造性を向上させた圧縮成型製剤およびその製造方法に関する。 The present invention relates to a compression-molded preparation such as an orally disintegrating tablet and a method for producing the same. More specifically, the present invention has excellent disintegrability in the oral cavity while having hardness that does not cause wear during production and transportation. Furthermore, the present invention relates to a compression-molded preparation with improved manufacturability in existing facilities and a method for producing the same.
現在、医薬品の剤形として、簡便性や服用容易性の面から、錠剤、カプセル剤、顆粒、粉末等の経口剤が最も汎用されている。しかし、このような経口製剤の多くは、高齢者、小児や嚥下困難な患者にとって服用しづらいという問題があった。 Currently, oral preparations such as tablets, capsules, granules, and powders are most widely used as pharmaceutical dosage forms from the viewpoint of simplicity and ease of administration. However, many of such oral preparations have a problem that it is difficult to take for elderly people, children and patients who have difficulty swallowing.
このため、服用を容易とするために、服用にあたって、水に懸濁し、シロップとすることのできるドライシロップ剤等も提供されているが、この製剤が粉末または顆粒状の形態の場合には、一回服用量毎に包装してあっても、包装内への内容物の残留や、開封時にその一部をこぼしてしまう等の恐れがあり、適正量を服用するには問題があった。 For this reason, dry syrups and the like that can be suspended in water and made into syrups are also provided for ease of taking, but when this preparation is in the form of powder or granules, Even if each dose is packaged, the contents may remain in the package, or a part of the package may be spilled when opened, and there is a problem in taking an appropriate amount.
そこで、近年、服用性の問題を解決する目的で、水なしでも服用でき、口腔内で速やかに崩壊する錠剤ないしトローチ剤や、水に溶解して服用する場合にも速やかに水性溶媒に溶ける錠剤ないしトローチ剤の開発が進められている。 Therefore, in recent years, tablets or lozenges that can be taken without water and quickly disintegrate in the oral cavity, or tablets that dissolve quickly in an aqueous solvent when taken in water for the purpose of solving the problem of dosing. The development of lozenges is ongoing.
例えば、上記のような錠剤ないしトローチ剤の製造方法として、粒子表面が湿潤する程度の水分を含む混合物を打錠する口腔内崩壊錠の製造方法(特許文献1)や、非晶質糖類を主体とし、低圧で圧縮成型した後、加湿下に錠剤を置き湿潤させ、更に乾燥する口腔内崩壊錠の製造方法(特許文献2及び3)が知られている。しかし、これらの技術は、いずれも、水性溶媒中での速やかな崩壊性や、携帯に必要な硬度が一応保たれた製剤が得られるものの、製造工程中における水分の取扱や、高湿度下での放置を必要とするなど、使用する生理活性成分との関係で、安定性に問題を来す可能性があり、また、製造工程管理の点から、必ずしも満足できるものではなかった。その上、従来技術での製剤調製にあたっては、圧縮成型の際の圧力を一定に調製する必要があり、製造条件の設定が複雑となるという問題があった。 For example, as a method for producing a tablet or a troche as described above, a method for producing an orally disintegrating tablet (Table 1) that compresses a mixture containing water at a level where the particle surface is moistened, or an amorphous saccharide is mainly used. In addition, a method for producing an orally disintegrating tablet (Patent Documents 2 and 3) is known in which a tablet is compression-molded at a low pressure, moistened and moistened, and further dried. However, all of these technologies are capable of rapid disintegration in aqueous solvents and preparations that retain the hardness required for portability, but they can handle moisture during the manufacturing process and under high humidity. In view of the relationship with the physiologically active ingredient to be used, there is a possibility that it may cause a problem in stability, and it is not always satisfactory from the viewpoint of manufacturing process management. In addition, in preparation preparations according to the prior art, it is necessary to adjust the pressure at the time of compression molding to be constant, and there is a problem that the setting of manufacturing conditions becomes complicated.
これに対し、本発明者らは、先に、糖にメタケイ酸アルミン酸マグネシウムをコーティングした顆粒を用いることにより、製造工程中における水分の取扱や、高湿度下での放置、特殊な製造工程等を必要とせず、通常の製造方法により口腔内崩壊錠が得られることを見出し、特許出願した(特許文献4)。 On the other hand, the present inventors have previously used granules in which sugar is coated with magnesium aluminate metasilicate, thereby handling moisture during the manufacturing process, leaving it under high humidity, special manufacturing processes, etc. Was found that an orally disintegrating tablet can be obtained by an ordinary production method (Patent Document 4).
しかしながら、口腔内崩壊錠等の圧縮成型製剤を製造するにあたっては、さらに生産性を向上することが求められていた。すなわち、錠剤の一般的な製造方法として、工程を簡略化するため、原材料となる添加剤を混合し、直接打錠する方法(直打法)や、添加する生理活性物質の含有量の均一性を担保するために、一旦顆粒を形成し打錠する方法が用いられる。しかし、直打法の場合には、原材料となる粉体の取扱に困難を伴うことがあり、又、顆粒を形成してから打錠する方法の場合は、一定以下の粒子径の粒が増えることに起因する粉末飛散等によって生産性低下を招くという欠点があった。さらに、圧縮成型製剤を製造する場合には、杵付着、キャッピング、ラミネーション、ダイフリクション等の打錠障害を抑えるために、通常よりも圧縮成型に時間をかける必要があった。そのため、単位時間あたりの錠剤生産数が通常の錠剤に比べ少ないために生産性が劣るという問題があった。更に、錠剤の硬度を十分に管理できなかった場合には、生産、輸送時の破損を招き、歩留まりが低下するという問題があった。 However, in producing a compression-molded preparation such as an orally disintegrating tablet, further improvement in productivity has been demanded. That is, as a general manufacturing method of tablets, in order to simplify the process, additives that are raw materials are mixed and directly compressed (direct compression method), and the content of the physiologically active substance to be added is uniform. In order to ensure the above, a method of once forming granules and tableting is used. However, in the case of the direct compression method, it may be difficult to handle the powder as the raw material, and in the case of the method of tableting after forming the granule, the number of particles having a certain particle size or less increases. In particular, there is a drawback that the productivity is reduced due to powder scattering and the like. Furthermore, in the case of producing a compression molding preparation, it has been necessary to spend more time for compression molding than usual in order to suppress tableting troubles such as wrinkle adhesion, capping, lamination, and die friction. For this reason, there is a problem that productivity is inferior because the number of tablets produced per unit time is smaller than that of normal tablets. Further, when the hardness of the tablet cannot be sufficiently controlled, there is a problem that the yield is lowered due to damage during production and transportation.
本発明者は、上記した製造上の問題を解決する技術として、担体成分に全部又は一部がデルタ型結晶であるマンニトールを使用することにより、圧縮成型時間を短縮しても、口腔内での速やかな崩壊性と生産、輸送に耐えうる硬度を有する圧縮成型製剤である口腔内崩壊錠が得られ、また、造粒時の微紛の量が減少することにより粉末飛散を抑制でき、さらに、圧縮成型性が向上することにより生産、輸送時における製剤の損傷を減少できることを見出し、特許出願した(特許文献5)。しかしながら、この発明を利用しても、通常の打錠に比べ、圧縮成型機の時間当たりの製造数量を少なくしたり、通常の圧縮成型では使用しない外部滑沢装置等の特殊な機械を使用しないと圧縮成型ができなかった。したがって、実際に経済性の高い圧縮成型製剤の製造法としては、まだ改善の余地のあるものであった。 As a technique for solving the above-described manufacturing problems, the present inventor uses mannitol, which is entirely or partially delta-type crystals, as a carrier component, so that even if the compression molding time is shortened, An orally disintegrating tablet that is a compression-molded preparation having a hardness that can withstand rapid disintegration, production, and transportation can be obtained, and powder scattering can be suppressed by reducing the amount of fine powder during granulation, The inventors found that damage to the preparation during production and transportation can be reduced by improving the compression moldability, and filed a patent application (Patent Document 5). However, even if this invention is used, the production quantity per hour of the compression molding machine is reduced as compared with normal tableting, or a special machine such as an external lubrication device that is not used in normal compression molding is not used. And compression molding was not possible. Therefore, there is still room for improvement as a method for producing a compression-molded preparation with high economic efficiency.
したがって、圧縮成型製剤の製造において、口腔内での速やかな崩壊性を有しながら、生産、輸送等に必要な硬度を兼ね備えると同時に、特殊な装置を使用しなくても高い生産性を確保できるような技術の提供が求められており、このような技術を提供することが本発明の課題である。 Therefore, in the production of compression-molded preparations, it has the necessary hardness for production, transportation, etc. while having rapid disintegration properties in the oral cavity, and at the same time, high productivity can be secured without using special equipment. The provision of such a technique is demanded, and it is an object of the present invention to provide such a technique.
本発明者らは、圧縮成型製剤に関し鋭意研究を行っていたところ、マンニトール等の糖アルコールを、デンプンあるいはデンプン由来加工物と、ポリビニルアルコール等特定のポリマー系結合剤を含む溶液を用いて造粒することにより、口腔内崩壊錠として優れた崩壊性と十分な硬度を兼ね備えた圧縮成型製剤が、極めて高速の打錠条件でも得られることを見出し、本発明を完成した。 The inventors of the present invention have been diligently researching on a compression molding preparation, and granulating sugar alcohol such as mannitol using a solution containing starch or a starch-derived processed product and a specific polymer binder such as polyvinyl alcohol. As a result, it was found that a compression-molded preparation having excellent disintegration properties and sufficient hardness as an orally disintegrating tablet can be obtained even under extremely high-speed tableting conditions, and the present invention has been completed.
すなわち本発明は、糖アルコール、デンプン若しくはデンプン由来化合物並びにポリビニルアルコール系ポリマーおよびコポリビドンからなる群から選ばれるポリマー系結合剤を含有する圧縮成型製剤である。 That is, the present invention is a compression-molded preparation containing a sugar-based alcohol, starch or a starch-derived compound, and a polymer-based binder selected from the group consisting of a polyvinyl alcohol-based polymer and copolyvidone.
また本発明は、糖アルコールを、デンプン若しくはデンプン由来化合物と、ポリビニルアルコール系ポリマーおよびコポリビドンからなる群から選ばれるポリマー系結合剤とを溶解した水溶液で造粒して顆粒となし、次いでこれを圧縮成型することを特徴とする圧縮成型製剤の製造方法である。 In the present invention, the sugar alcohol is granulated with an aqueous solution in which starch or a starch-derived compound and a polymer binder selected from the group consisting of a polyvinyl alcohol polymer and copolyvidone are dissolved to form granules, and then compressed. A method for producing a compression-molded preparation characterized by molding.
本発明によれば、高速打錠機を用い、50,000錠/時を上回る速度で打錠しても、特殊な装置を必要とせず、杵付着、キャッピング、ダイフリクション等の打錠障害を起こすことなく、崩壊性と硬度を両立した圧縮成型製剤を得ることができる。また、高速打錠であっても、打錠圧を適宜調製することにより、製剤の硬度あるいは口腔内での崩壊時間を調節することが可能である。 According to the present invention, even if tableting is performed at a speed exceeding 50,000 tablets / hour using a high-speed tableting machine, no special device is required, and tableting troubles such as sticking, capping, and die friction are prevented. A compression-molded preparation having both disintegration and hardness can be obtained without causing it. Even for high-speed tableting, the hardness of the preparation or the disintegration time in the oral cavity can be adjusted by appropriately adjusting the tableting pressure.
このように、本発明により、口腔内での適切な崩壊性と適度な硬度を有する口腔内崩壊錠等の圧縮成型製剤を高速で調製できるため、生産時間の短縮、収率の向上、歩留まりの向上等が可能となり、生産性を大幅に向上させることができる。 As described above, according to the present invention, since it is possible to prepare a compression-molded preparation such as an orally disintegrating tablet having appropriate disintegration property and appropriate hardness in the oral cavity at high speed, production time is shortened, yield is improved, and yield is increased. Improvements can be made, and productivity can be greatly improved.
本発明の圧縮成型製剤において使用される糖アルコールとしては、例えば、マンニトール、キシリトール、ソルビトール、エリスリトール等が挙げられ、このうちマンニトールが好ましい。更に、糖アルコールとしてマンニトールを使用する場合、全部のマンニトールがデルタ型であるか、マンニトールの一部がデルタ型のもので、それ以外は他の結晶型であることが好ましい。 Examples of the sugar alcohol used in the compression-molded preparation of the present invention include mannitol, xylitol, sorbitol, erythritol, etc. Among them, mannitol is preferable. Further, when mannitol is used as the sugar alcohol, it is preferable that all mannitol is delta type, or a part of mannitol is delta type, and other crystal forms are other than that.
すなわち、マンニトールには、X線回折の結果より識別される、アルファー、ベータ、デルタ型の結晶多形が存在することが知られているが、このうちのデルタ型マンニトールが杵臼間のきしみ等を減らすなどの作用を有するため、少なくとも一部にデルタ型マンニトールが含まれていることが望ましい。 In other words, it is known that mannitol has alpha, beta, and delta crystal polymorphs that are identified from the results of X-ray diffraction. It is desirable that at least a part of delta mannitol is contained in order to have an action such as reduction.
糖アルコールとしてマンニトールを使用する場合、デルタ型マンニトールの量は、特段限定されるものではないが、全体のマンニトールの3質量%(以下、単に「%」で示す)以上、好ましくは5%以上であり、より好ましくは10%以上、更に好ましくは20%以上である。 When mannitol is used as the sugar alcohol, the amount of delta-type mannitol is not particularly limited, but is 3% by mass (hereinafter simply referred to as “%”) or more, preferably 5% or more of the whole mannitol. Yes, more preferably 10% or more, still more preferably 20% or more.
また、本発明に使用するデンプン若しくはデンプン由来化合物(以下、「デンプン類」という)は、常温で水に溶解若しくは膨潤する結合剤(以下、単に「結合剤」ということがある)として利用されるものである。 The starch or starch-derived compound (hereinafter referred to as “starch”) used in the present invention is used as a binder that dissolves or swells in water at room temperature (hereinafter sometimes simply referred to as “binder”). Is.
このデンプン類のうち、デンプン由来化合物は、何らかの方法で通常は水に溶解されないデンプンが全部若しくは一部溶解される状態になっているものであり、具体的には、デンプンのアルファー化物や加水分解物が挙げられる。 Among these starches, starch-derived compounds are those in which starch, which is not normally dissolved in water, is dissolved in whole or in part by some method. Specifically, starch starch is pregelatinized or hydrolyzed. Things.
なお、アルファー化とは水に浸透させたデンプンを加熱することにより結晶構造を維持するための水素結合が切断され、水が結晶構造に入り込む状態を指す。具体的にはデンプンを水に懸濁させ、その懸濁液を加熱することによりアルファー化することができる。また、アルファー化されたデンプンには、少なくともその一部がアルファー化されたデンプン、すなわち、実質的にアルファー化されたデンプンも含む。 In addition, pregelatinization refers to a state in which water enters the crystal structure by breaking the hydrogen bond for maintaining the crystal structure by heating the starch soaked in water. Specifically, starch can be suspended in water and the suspension can be heated to alpha. Pregelatinized starch also includes starch that is at least partially pregelatinized, that is, substantially pregelatinized starch.
また、現在はアルファー化された化合物としてアルファー化デンプンが市販されているので、これを利用することもできる。また、実質的にアルファー化されたデンプンとして、部分アルファー化デンプンが市販されているので、これを利用しても良い。 In addition, since pregelatinized starch is commercially available as a pregelatinized compound, it can be used. Further, since partially pregelatinized starch is commercially available as substantially pregelatinized starch, it may be used.
更に、デンプンが加水分解された添加剤も「デンプン類」であり、本発明に十分に利用可能である。このようなデンプン加水分解物の具体例としては、デキストリンが挙げられる。更にまた、黒酵母の一種であるオーレオバシディウム・プルランス(Aureobasidium pullulans)を培養して得られた、マルトトリオースが規則正しくα-1,6結合した天然多糖類であるプルランについても本特許の効果を十分に発揮する。Furthermore, additives obtained by hydrolyzing starch are also “starches” and can be fully used in the present invention. A specific example of such a starch hydrolyzate is dextrin. Furthermore, this patent also relates to pullulan, which is a natural polysaccharide in which maltotriose is regularly α-1,6-linked, obtained by culturing Aureobasidium pullulans , a kind of black yeast. Fully demonstrate the effect.
更に、本発明で利用するポリビニルアルコール系ポリマーやコポリビドンも、結合剤として作用するものである(以下、これらを総称して「ポリマー系結合剤」ということがある)。 Furthermore, the polyvinyl alcohol-based polymer and copolyvidone used in the present invention also act as a binder (hereinafter, these may be collectively referred to as “polymer-based binder”).
このうち、ポリビニルアルコール系ポリマーとは、後述するポリビニルアルコール若しくはビニルアルコールと他のモノマーのコポリマーである。そのうち、ポリビニルアルコールのコポリマーとしては、グラフトコポリマーのように主鎖の一部から別のポリマーが分岐するコポリマーや、ランダムコポリマーのようにポリマーの構成単位が無秩序に配列しているようなコポリマー、あるいはブロックコポリマー等が挙げられる。グラフトコポリマーの具体例としてはポリビニルアルコール−ポリエチレングリコールグラフトコポリマーが、ランダムコポリマーの具体的な例としてポリビニルアルコール−アクリルコポリマーが挙げられる。 Among these, the polyvinyl alcohol-based polymer is polyvinyl alcohol or a copolymer of vinyl alcohol and other monomers described later. Among them, as a copolymer of polyvinyl alcohol, a copolymer in which another polymer branches from a part of the main chain such as a graft copolymer, a copolymer in which polymer structural units are randomly arranged, such as a random copolymer, or Examples thereof include block copolymers. Specific examples of the graft copolymer include polyvinyl alcohol-polyethylene glycol graft copolymer, and specific examples of the random copolymer include polyvinyl alcohol-acrylic copolymer.
上記ポリマー系結合剤のうち、ポリビニルアルコールとしては、その分子量が10,000ないし300,000程度のもの、特に、30,000ないし200,000程度のものが好ましい。このポリビニルアルコールは、酢酸ビニルを重合し、これをケン化することにより製造または入手することができる。なお、ケン化の度合いにより、完全ケン化型と部分ケン化型に分類されるが、本発明はどちらのポリビニルアルコールを使用しても、本発明の効果を十分に発揮する。 Among the above-mentioned polymer binders, polyvinyl alcohol having a molecular weight of about 10,000 to 300,000, particularly about 30,000 to 200,000 is preferable. This polyvinyl alcohol can be produced or obtained by polymerizing vinyl acetate and saponifying it. The saponification type is classified into a complete saponification type and a partial saponification type, but the present invention sufficiently exhibits the effect of the present invention regardless of which polyvinyl alcohol is used.
また、前記ポリマー系結合剤のうち、ポリビニルアルコール−ポリエチレングリコールグラフトコポリマーは、下記式(I)で表されるように、主鎖がポリエチレングリコール(PEG)部分、側鎖がポリビニルアルコール(PVA)部分で構成されるPEGとPVAのグラフトコポリマーである。 Among the polymer-based binders, the polyvinyl alcohol-polyethylene glycol graft copolymer is represented by the following formula (I), the main chain is a polyethylene glycol (PEG) portion, and the side chain is a polyvinyl alcohol (PVA) portion. It is a graft copolymer of PEG and PVA composed of
このポリビニルアルコール−ポリエチレングリコールグラフトコポリマーとしては、その分子量が10,000ないし100,000程度のもの、特に30,000ないし70,000程度のものが好ましい。また、このポリビニルアルコール−ポリエチレングリコールグラフトコポリマーは、PEG部分とPVA部分の重量比が、1:0.1ないし10のものが好ましい。このポリビニルアルコール−ポリエチレングリコールグラフトコポリマーとしては、BASF社製からコリコートIR(商品名)が市販されているので、これを用いることができるが、その他の製品を用いてもよい。 The polyvinyl alcohol-polyethylene glycol graft copolymer preferably has a molecular weight of about 10,000 to 100,000, particularly about 30,000 to 70,000. The polyvinyl alcohol-polyethylene glycol graft copolymer preferably has a PEG moiety to PVA moiety weight ratio of 1: 0.1 to 10. As this polyvinyl alcohol-polyethylene glycol graft copolymer, since Kollicoat IR (trade name) is commercially available from BASF, it can be used, but other products may also be used.
更に、ポリマー系結合剤のうち、ポリビニルアルコール−アクリルコポリマーは、下記式(II)で表されるように、PVA、アクリル酸およびメチル(メタ)アクリレートを含むコポリマーである。 Further, among the polymer binders, the polyvinyl alcohol-acrylic copolymer is a copolymer containing PVA, acrylic acid and methyl (meth) acrylate as represented by the following formula (II).
このポリビニルアルコール−アクリルコポリマーは、その分子量が、10,000ないし200,000程度のもの、特に30,000ないし100,000程度のものが好ましい。このポリビニルアルコールコポリマーの、PVAと、アクリル酸およびメタクリル酸メチルの重量比は、1:0.01ないし0.1:0.1ないし0.5のものが好ましい。このポリビニルアルコール−アクリルコポリマーとしては、日新化成社製からPOVACOAT(商品名)が市販されているので、これを用いることができるが、その他の製品を用いてもよい。 The polyvinyl alcohol-acrylic copolymer preferably has a molecular weight of about 10,000 to 200,000, particularly about 30,000 to 100,000. The polyvinyl alcohol copolymer preferably has a weight ratio of PVA to acrylic acid and methyl methacrylate of 1: 0.01 to 0.1: 0.1 to 0.5. As this polyvinyl alcohol-acrylic copolymer, POVACOAT (trade name) manufactured by Nisshin Kasei Co., Ltd. is commercially available. This can be used, but other products may also be used.
更にまた、ポリマー系結合剤のうち、コポリビドンは、下記式(III)で表されるように、1−ビニル−2−ピロリドンと酢酸ビニルの共重合体である。 Furthermore, among the polymer binders, copolyvidone is a copolymer of 1-vinyl-2-pyrrolidone and vinyl acetate as represented by the following formula (III).
このコポリビドンとしては、その分子量が、10,000ないし100,000程度のもの、特に45,000ないし70,000程度のものが好ましい。このコポリビドンの、1−ビニル−2−ピロリドンと酢酸ビニルの重量比は特に限定されないが、1:5ないし0.1が好ましく、更に好ましくは1:1ないし0.5が好ましい。このコポリビドンとしては、BASF社製からコリドンVA64(商品名)が市販されているので、これを用いることができるが、その他の製品を用いてもよい。 The copolyvidone preferably has a molecular weight of about 10,000 to 100,000, particularly about 45,000 to 70,000. The weight ratio of 1-vinyl-2-pyrrolidone to vinyl acetate in this copolyvidone is not particularly limited, but is preferably 1: 5 to 0.1, more preferably 1: 1 to 0.5. As this copolyvidone, Kollidon VA64 (trade name) is commercially available from BASF, and can be used, but other products may also be used.
本発明の圧縮成型製剤での、糖アルコールの配合量は、製剤中30ないし98%程度であり、50ないし95%が好ましい。また、デンプン類の配合量は、製剤中0.01ないし10%程度、好ましくは、0.05ないし5%程度、ポリマー系結合剤の配合量は、製剤中0.01ないし10%程度、好ましくは、0.05ないし2%程度である。また、糖アルコールに対するデンプン類の配合比率は、糖アルコール100に対して0.1ないし5であることが好ましく、糖アルコールに対するポリマー系結合剤の配合比率は、糖アルコール100に対して0.5ないし10であることが好ましい。 In the compression-molded preparation of the present invention, the amount of sugar alcohol is about 30 to 98%, preferably 50 to 95% in the preparation. Further, the compounding amount of starches is about 0.01 to 10% in the preparation, preferably about 0.05 to 5%, and the amount of the polymer binder is about 0.01 to 10% in the preparation, preferably Is about 0.05 to 2%. In addition, the blending ratio of starch to sugar alcohol is preferably 0.1 to 5 with respect to sugar alcohol 100, and the blending ratio of polymer binder to sugar alcohol 100 is 0.5 to sugar alcohol 100. Or 10 is preferred.
上記した各成分を用いて本発明の圧縮成型製剤を調製する好ましい方法の例としては、まず、デンプン類およびポリマー系結合剤を精製水等の溶媒に溶解若しくは懸濁させ、この溶解若しくは懸濁液を用いてマンニトール等の糖アルコールを造粒する方法が挙げられる。 As an example of a preferable method for preparing the compression-molded preparation of the present invention using each of the above-mentioned components, first, starches and a polymer binder are dissolved or suspended in a solvent such as purified water, and this dissolution or suspension is performed. The method of granulating sugar alcohols, such as a mannitol, using a liquid is mentioned.
この場合に用いられる造粒装置としては、通常の打錠用顆粒のように粒状物を微粉が殆ど無い状態で形成できる造粒機であれば特段限定されることはない。しかし、生産性等を考慮すると、好ましくは流動層造粒機、攪拌造粒機、押出造粒機、転動造粒機、ワースター造粒機若しくはこれらを組み合わせた造粒機が挙げられ、最良な造粒機としては流動層造粒機が挙げられる。 The granulating apparatus used in this case is not particularly limited as long as it is a granulator capable of forming a granular material with almost no fine powder like ordinary tableting granules. However, in consideration of productivity, etc., preferably a fluidized bed granulator, a stirring granulator, an extrusion granulator, a rolling granulator, a Wurster granulator, or a granulator that combines these is best. Examples of such granulators include fluidized bed granulators.
このようにして造粒された造粒物は、次いで圧縮成型され、製剤化される。この圧縮成型は、一般の圧縮成型の方法であれば特に限定なく利用することができる。例えば、糖アルコールとしてのマンニトール等、デンプン類、ポリマー系結合剤および生理活性物質と、必要に応じて配合される無機塩類や他の任意成分を混合した粉体から調製される顆粒剤を、通常の打錠機、例えば、ロータリー式打錠機、単発打錠機等で圧縮成型することにより、圧縮成型製剤を調製することが可能である。 The granulated product thus granulated is then compression molded and formulated. This compression molding can be used without particular limitation as long as it is a general compression molding method. For example, a granule prepared from a powder prepared by mixing mannitol as a sugar alcohol, starches, a polymer-based binder, and a physiologically active substance, and inorganic salts and other optional components blended as necessary. It is possible to prepare a compression-molded preparation by compression molding using a tableting machine such as a rotary tableting machine or a single-shot tableting machine.
なお、実生産を考慮すると、好ましい圧縮成型機はロータリー式打錠機である。この場合、実生産に伴うのであれば、圧縮成形の時間当たりの生産性については特段制限されるものではないが、好ましくは1時間当たり50,000錠以上であり、更に好ましくは100,000錠以上である。ロータリー打錠機はターンテーブルの回転数により圧縮成型時間が変化するため、打錠特性に大きな影響を与える。また、ターンテーブルの回転数と共に、ターンテーブルの大きさについても、打錠特性の影響を与えることが知られている。 In consideration of actual production, a preferred compression molding machine is a rotary tableting machine. In this case, as long as actual production is involved, the productivity per hour of compression molding is not particularly limited, but is preferably 50,000 tablets or more per hour, more preferably 100,000 tablets. That's it. The rotary tableting machine greatly affects the tableting characteristics because the compression molding time varies depending on the number of rotations of the turntable. It is also known that the size of the turntable as well as the rotation speed of the turntable affects the tableting characteristics.
したがって、これらのファクターを調整することにより生産能力にも差が出てくる。通常、ターンテーブルの回転数が低い若しくはその半径が短いほうが打錠障害の発生がなく、安定に生産ができる。反面、回転数が低い若しくは/且つターンテーブルの半径が短いと時間当たりの生産性が落ちるため、実生産にそぐわない。したがって、ターンテーブルの時間当たりの回転数(rpm)の二乗とターンテーブルの半径(この場合の半径は中心から臼の中心までの距離(m))の積で表したとき、50以上、好ましくは80以上、更に好ましくは150以上の条件で打錠した場合に実生産に適している。 Therefore, by adjusting these factors, there will be a difference in production capacity. Usually, the lower the rotation speed of the turntable or the shorter the radius, there is no occurrence of tableting trouble and stable production can be achieved. On the other hand, if the rotational speed is low and / or the radius of the turntable is short, the productivity per hour falls, so it is not suitable for actual production. Therefore, when expressed by the product of the square of the number of revolutions per hour (rpm) of the turntable and the radius of the turntable (in this case, the radius is the distance (m) from the center to the center of the die), preferably 50 or more, preferably It is suitable for actual production when tableting is performed under conditions of 80 or more, more preferably 150 or more.
また、圧縮成型を行う際の圧力についても口腔内での崩壊時間、テクスチャーが適切で、製造時、運搬時での割れ欠け等がなければ特に限定されることはなく、好ましくは100〜2000kgf、更に好ましくは300〜1500kgfで圧縮成型される。 Further, the pressure at the time of compression molding is not particularly limited as long as the disintegration time and texture in the oral cavity are appropriate, and there are no cracks at the time of production and transportation, preferably 100 to 2000 kgf, More preferably, it is compression molded at 300 to 1500 kgf.
更に、本発明の圧縮成型製剤は口腔内崩壊錠化することも可能である。本発明の口腔内崩壊錠とは圧縮成型製剤を口腔内に含ませた場合、速やかに崩壊すればよく、具体的な崩壊時間としては、口腔内に含ませてから3分以内であり、好ましくは1分以内であり、更に好ましくは30秒以内である。そして、今回発明に至った口腔内崩壊錠は輸送等の割れ、欠けに対して、今まで以上に向上されたものであり、通常の圧縮成型製剤と同様の耐久性を付与している。これらを検証する指標としては、第15改正日本薬局方に記載されている錠剤の摩損度試験法を利用して評価される。 Furthermore, the compression-molded preparation of the present invention can be made into an orally disintegrating tablet. The orally disintegrating tablet of the present invention may be rapidly disintegrated when a compression-molded preparation is included in the oral cavity, and the specific disintegration time is preferably within 3 minutes after being included in the oral cavity. Is within 1 minute, more preferably within 30 seconds. And the orally disintegrating tablet which reached this invention is improved more than before with respect to the cracks, chipping, etc. of transportation etc., and has provided the durability similar to a normal compression molding formulation. As an index for verifying these, evaluation is carried out using the tablet friability test method described in the 15th revised Japanese Pharmacopoeia.
具体的には第15改正日本薬局方に記載されている摩損度試験機に圧縮成型した錠剤を100錠入れ、30分間装置を稼動させる。次いで試験の前後における錠剤重量を測定し、錠剤重量の減少率を下式により求める。その結果、錠剤重量の減少率が5.0%以下のものが本発明の好ましい圧縮成型製剤であり、更に2.0%以下、特に1.0%以下の圧縮成型製剤が好ましい。 Specifically, 100 tablets that are compression-molded are put into a friability tester described in the 15th revision Japanese Pharmacopoeia, and the apparatus is operated for 30 minutes. Next, the tablet weight before and after the test is measured, and the reduction rate of the tablet weight is determined by the following equation. As a result, a tablet weight reduction rate of 5.0% or less is a preferred compression molding preparation of the present invention, and a compression molding preparation of 2.0% or less, particularly 1.0% or less is preferred.
減少率(%)=(試験前の重量−試験後の重量)/試験前の重量×100 Decrease rate (%) = (weight before test−weight after test) / weight before test × 100
本発明の圧縮成型製剤の製造に当たっては、前記したデンプン類およびポリマー系結合剤に加え、公知の他の結合剤を使用することもできる。このような結合剤の好ましいものとしては、セルロースの一部を親水性の置換基に置換させることにより水に溶解できるようにした化合物、デンプン類を加水分解、アルファー化させることにより水に溶解できるようにした化合物またはセルロース、デンプン等を微生物等により化学変化した物質等が挙げられる。具体的には、ヒドロキシプロピルセルロース、ヒドロキシエチルセルロース、ヒドロキシプロピルメチルセルロース、カルメロースナトリウム、デキストリン、プルラン、可溶性ポリビニルピロリドン等が挙げられる。 In the production of the compression-molded preparation of the present invention, other known binders can be used in addition to the starches and polymer binders described above. Preferred examples of such a binder include a compound that can dissolve in water by substituting a part of cellulose with a hydrophilic substituent, and can be dissolved in water by hydrolyzing and pregelatinizing starches. Examples include compounds obtained by chemically changing cellulose, starch, and the like as described above with microorganisms. Specific examples include hydroxypropylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, carmellose sodium, dextrin, pullulan, and soluble polyvinylpyrrolidone.
更に、無機化合物の添加方法についても特段限定するものではなく、例えば、マンニトール等の糖アルコールと共に、造粒時に添加する方法、結合剤液(造粒液)に添加する方法、造粒後の顆粒に添加する方法などがある。また、糖アルコールとデンプン類およびポリマー系結合剤との造粒物に無機化合物をコーティングする方法を採用しても良い。これらのうち、好ましい方法としては結合剤液に添加する方法、造粒後の顆粒にコーティングする方法、造粒後の顆粒に添加する方法であり、最良の方法としてはマンニトールと常温で水に溶解若しくは膨潤する結合剤の造粒物にコーティングする方法若しくは造粒後に添加する方法である。 Furthermore, the addition method of the inorganic compound is not particularly limited. For example, together with sugar alcohol such as mannitol, a method of adding during granulation, a method of adding to a binder liquid (granulation liquid), a granule after granulation There is a method of adding to. Moreover, you may employ | adopt the method of coating an inorganic compound on the granulated material of sugar alcohol, starches, and a polymer type binder. Among these, the preferred method is the method of adding to the binder solution, the method of coating the granules after granulation, the method of adding to the granules after granulation, and the best method is dissolving in mannitol and water at room temperature. Alternatively, it is a method of coating on a granulated product of a swelling binder or a method of adding after granulation.
本発明の圧縮成型製剤は、基本的に有効成分としての生理活性物質を含有させるものである。圧縮成型製剤への生理活性物質の配合は、圧縮成型製剤の製造の何れの段階で行っても良く、例えば、生理活性成分を糖アルコールと共に、造粒時に配合する方法、結合剤液中に添加する方法、造粒した顆粒と共に配合する方法等を挙げることができる。 The compression-molded preparation of the present invention basically contains a physiologically active substance as an active ingredient. The compounding of the physiologically active substance into the compression molding preparation may be carried out at any stage of the production of the compression molding preparation. For example, a method of blending a physiologically active ingredient together with sugar alcohol at the time of granulation, or adding to a binder solution And a method of blending with granulated granules.
更にまた、有効成分として配合することのできる生理活性成分としても、特に限定されることはなく、例えば、睡眠鎮静剤、抗不安剤、抗てんかん剤、解熱鎮痛剤、抗パーキンソン剤、精神神経用剤、自律神経剤、鎮けい剤、強心剤、不整脈用剤、利尿剤、血圧降下剤、血管収縮剤、血管拡張剤、高脂血症用剤、鎮咳剤、去たん剤、気管支拡張剤、止瀉剤、消化性潰瘍用剤、健胃消化剤、制酸剤、下剤、ホルモン剤、ビタミン剤、滋養強壮剤、酵素製剤、糖尿病用剤、抗ヒスタミン剤、アレルギー剤、抗生物質製剤、合成抗菌剤、酔い止め剤等の有効成分である生理活性成分が利用できる。 Furthermore, the physiologically active ingredient that can be blended as an active ingredient is not particularly limited. For example, a sleep sedative, an anxiolytic agent, an antiepileptic agent, an antipyretic analgesic agent, an antiparkinsonian agent, and a neuropsychiatric agent Agent, autonomic agent, antispasmodic agent, cardiotonic agent, arrhythmic agent, diuretic agent, antihypertensive agent, vasoconstrictor, vasodilator, hyperlipidemia agent, antitussive agent, expectorant, bronchodilator, antipruritic agent , Peptic ulcer agent, stomach digestive agent, antacid, laxative, hormone agent, vitamin agent, nourishing tonic, enzyme preparation, diabetic agent, antihistamine, allergic agent, antibiotic preparation, synthetic antibacterial agent, sickness prevention A physiologically active ingredient which is an active ingredient such as an agent can be used.
このうち、睡眠鎮静剤、抗不安剤の生理活性成分としては、例えば、アルプラゾラム、エスタゾラム、クアゼパム、トリアゾラム、ブロチゾラム、アモバルビタール、タンドスピロン等が、抗てんかん剤の生理活性成分としては、例えば、フェニトイン、カルバマゼピン、クロナゼパム、フェニトイン等が、解熱鎮痛剤の生理活性成分としては、例えば、アセトアミノフェン、フェナセチン、メフェナム酸、アスピリン、エテンザミド、イソプロピルアンチピリン、サリチル酸ナトリウム、インドメタシン、ジクロフェナク、チアラミド、アクタリット、アンピロキシカム、イブプロフェン、エトドラク、ケトプロフェン、ザルトプロフェン、ピロキシカム、プラノプロフェン、ロキソプロフェン等が、抗パーキンソン剤の生理活性成分としては、例えば、アマンタジン、ビペリデン、セレギリン、トリヘキシフェニジル、カベルゴリン、ペルゴリド等が、精神神経用剤の生理活性成分としては、例えば、クロルプロマジン、ペルフェナジン、トリプロペラジン、イミプラミン、エチゾラム、オランザピン、クアゼパム、スルピリド、ハロペリドール、リスペリドン等が、自律神経剤の生理活性成分としては、例えば、カルプロニウム、ジスチグミン、トラゾリン等が、鎮けい剤の生理活性成分としては、臭化ブチルスコポラミン、パパベリン、エペリゾン、チザニジン、バクロフェン等がそれぞれ挙げられる。 Of these, as physiologically active components of sleep sedatives and anxiolytic agents, for example, alprazolam, estazolam, quazepam, triazolam, brotizolam, amobarbital, tandospirone, etc., as physiologically active components of antiepileptic agents, for example, phenytoin, Carbamazepine, clonazepam, phenytoin, etc., as the physiologically active components of antipyretic analgesics, for example, acetaminophen, phenacetin, mefenamic acid, aspirin, ethenamide, isopropylantipyrine, sodium salicylate, indomethacin, diclofenac, thiaramide, actarit, ampiroxicam, Ibuprofen, etodolac, ketoprofen, zaltoprofen, piroxicam, pranoprofen, loxoprofen, etc. are the bioactive ingredients of antiparkinsonian drugs. Are, for example, amantadine, biperidene, selegiline, trihexyphenidyl, cabergoline, pergolide and the like, and the physiologically active components of the neuropsychiatric agent are, for example, chlorpromazine, perphenazine, triproperazine, imipramine, etizolam, olanzapine, quazepam , Sulpiride, haloperidol, risperidone, etc., as the physiologically active components of the autonomic agent, for example, carpronium, distigmine, torazoline, etc., as the physiologically active components of the antipruritic agent, butylscopolamine bromide, papaverine, eperisone, tizanidine, Baclofen and the like can be mentioned.
また、強心剤としては、例えば、ジキトキシン、ジゴキシン、メチルジゴキシン、アミノフィリン、カフェイン、エチレフリン、ユビデカレノン等が、不整脈用剤としては、例えば、プロカインアミド、アテノロール、オクスプレノロール、カルテオロール、プロプラノロール、ナドロール、ピンドロール、ビソプロロール、アジマリン、ピルジカイニド、プロパフェノン、メチシレチン、ジソピラミド等が、利尿剤としては、例えば、ヒドロクロロチアジド、スピロノラクトン、アセタゾラミド、イソソルビド、トラセミド、フロセミド等が、血圧降下剤としては、例えば、ヒドララジン、レセルピン、アラセプリル、イミダプリル、キナプリル、カプトプリル、シラザプリル、エナラプリル、リシノプリル、メチルドバ、エホニジピン、セリプロロール、ニカルジピン、プラゾシン、ベタキソロール、マニジピン、カルベジロール、メトプロロール、シルニジピン、フェロジピン、ドキサゾシン等が、血管収縮剤としては、例えば、ミドドリン、ジヒドロエルゴタミン等が、血管拡張剤としては、例えば、一硝酸イソソルビド、エタフェノン、ジルチアゼム、ベニジピン、ジピリダモール、硝酸イソソルビド、ニコランジル、ニソルジピン、ニトログリセリン、ニフェジピン等が、高脂血症用剤としては、例えば、クロフェブラート、フェノフィブラート、ベザフィブラート、アドルバスタチン、エラスターゼ、ニコモール、プラバスタチン、フルバスタチン、プロブコール、シンバスタチン等がそれぞれ挙げられる。 Examples of the cardiotonic agent include diquitoxin, digoxin, methyldigoxin, aminophylline, caffeine, ethylephrine, ubidecalenone, and examples of the arrhythmia agent include procainamide, atenolol, oxprenolol, carteolol, propranolol, and nadolol. , Pindolol, bisoprolol, azimarin, pirucainide, propaphenone, methiciletin, disopyramide, etc., as diuretics, for example, hydrochlorothiazide, spironolactone, acetazolamide, isosorbide, torasemide, furosemide, etc. , Alasepril, imidapril, quinapril, captopril, cilazapril, enalapril, lisinopril, methyldova, efonidipine, Riprolol, nicardipine, prazosin, betaxolol, manidipine, carvedilol, metoprolol, cilnidipine, felodipine, doxazosin and the like as vasoconstrictors, for example, middolin, dihydroergotamine, and the like as vasodilators, for example, isosorbide mononitrate, ethaphenone , Diltiazem, benidipine, dipyridamole, isosorbide nitrate, nicorandil, nisoldipine, nitroglycerin, nifedipine, and the like as hyperlipidemic agents, for example, clofebrate, fenofibrate, bezafibrate, adolvastatin, elastase, nicomol, pravastatin, Fluvastatin, probucol, simvastatin and the like can be mentioned.
更に、鎮咳剤としては、例えば、エフェドリン、メチルエフェドリン、ノスカピン、ベンプロペリン等が、去たん剤としては、例えば、カルボシステイン、ブロムヘキシン、アンブロキソール、桜皮、コデイン、ジヒドロコデイン、チペピジン等が、気管支拡張剤としては、例えば、テオフィリン、フェノテロール、サルブタモール、クレンブテロール、ツロブテロール、トリメトキノール、プロカテロール、ホルモテロール等が、止瀉剤・整腸剤としては、例えば、ベルベリン、アルブミン、ビフィズス菌、ラクトミン、ジメチコン、ロペラミド等が、消化性潰瘍剤としては、例えば、グルタミン、アズレン、ラニチジン、シメチジン、ファモチジン、ニザチジン、ロキサチジン、アルジオキサ、ピレンゼピン、オメプラゾール、ゲファルナート、スクラルファート、スルピリド、ソファルコン、テプレノン、トロキシピド、イルソグラジン、ラベプラゾール、ランソプラゾール等が、健胃消化剤としては、例えば、アミラーゼ、ジアスターゼ、パンクレアチン、ホミカチンキ、カルニチン、ガラクトシダーゼ等が、制酸剤としては、例えば、ケイ酸マグネシウム、酸化マグネシウム、炭酸水素ナトリウム、炭酸マグネシウム、沈降炭酸カルシウム等が、下剤としては、例えば、センナエキス、センノシド、硫酸マグネシウム、ピコスルファート等がそれぞれ挙げられる。 Furthermore, as antitussives, for example, ephedrine, methylephedrine, noscapine, benproperin and the like, and as an expectorant, for example, carbocysteine, bromhexine, ambroxol, cherry bark, codeine, dihydrocodeine, tipepidine and the like are bronchodilators. As, for example, theophylline, fenoterol, salbutamol, clenbuterol, tulobuterol, trimethoquinol, procaterol, formoterol, etc., as antidiarrheal agent / intestinal, for example, berberine, albumin, bifidobacteria, lactamine, dimethicone, loperamide, etc. Examples of the ulcer agent include glutamine, azulene, ranitidine, cimetidine, famotidine, nizatidine, loxatidine, aldioxa, pirenzepine, omeprazole, gefalu , Sucralfate, sulpiride, cefircon, teprenone, troxipide, irsogladine, rabeprazole, lansoprazole, etc., as a gastric digestive agent, for example, amylase, diastase, pancreatin, homicatin tincture, carnitine, galactosidase, etc. as antacids Examples include magnesium silicate, magnesium oxide, sodium hydrogen carbonate, magnesium carbonate, precipitated calcium carbonate, and examples of laxatives include senna extract, sennoside, magnesium sulfate, and picosulfate.
更にまた、ホルモン剤としては、例えば、レボチロキシン、リオチロニン、チアマゾール、プロピルリオウラシル、コルチゾン、パラメタゾン、デキサメタゾン、ベタメタゾン、プレドニゾロン、テストステロン、ホスフェストロール、エストリオール、クロルマジノン、アリルエストレノール、クロミフェン、タナゾール、タムスロシン、フラボキサート、ミドドリン、ガンマーオリザノール等が、ビタミン剤としては、例えば、ビタミンA、カルシトリオール、チアミン、フルスルチアミン、リボフラビン、パンテチン、パントテン酸、ピリドキシン、葉酸、コバマミド、メコバラミン、アスコルビン酸、トコフェロール、フィトナジオン、メナテトレノン、ビオチン等が、酵素製剤としては、例えば、リゾチーム、セラペプターゼ等が、糖尿病用剤としては、例えば、グリクラジド、グリベンクラミド、グリメピリド、トルブタミド、メトホルミン、アカルボース、ボグリボース等が、抗ヒスタミン剤としては、例えば、ジフェンヒドラミン、プロメタジン、メキタジン、クロルフェニラミン、クレマスチン等が、アレルギー用剤としては、例えば、イブジラスト、アゼラスチン、エピナスチン、セチリジン、スプラタスト、トラニラスト、ケトチフェン、プランルカスト、ペミロラスト、ロラタジン等がそれぞれ挙げられる。 Furthermore, as hormonal agents, for example, levothyroxine, liothyronine, thiamazole, propylliouracil, cortisone, parameterzone, dexamethasone, betamethasone, prednisolone, testosterone, phosfestol, estriol, chlormadinone, allylestrenol, clomiphene, tanazole, Tamsulosin, flavoxate, midodrine, gamma oryzanol, etc., as vitamin agents, for example, vitamin A, calcitriol, thiamine, fursultiamine, riboflavin, pantethine, pantothenic acid, pyridoxine, folic acid, cobamide, mecobalamin, ascorbic acid, tocopherol, Phytonadione, menatetrenone, biotin, etc., and examples of enzyme preparations include lysozyme, serrapeptase, etc. Examples of antidiabetic agents include gliclazide, glibenclamide, glimepiride, tolbutamide, metformin, acarbose, voglibose, etc., and antihistamines include, for example, diphenhydramine, promethazine, mequitazine, chlorpheniramine, clemastine, etc. Examples thereof include ibudilast, azelastine, epinastine, cetirizine, suplatast, tranilast, ketotifen, pranlukast, pemirolast, loratadine and the like.
また更に、抗生物質としては、例えば、クリンダマイシン、リンコマイシン、バンコマイシン、カナマイシン、アモキシシリン、アンピシリン、セファクロル、セファレキシン、セフィキシム、セフポドキシム、セフジニル、セフテラム、セフポドキシム、ホスホマイシン、ファロペネム、エリスロマイシン、アジスロマイシン、クラリスロマイシン、ロキシスロマイシン、クロラムフェニコール、テトラサイクリン、ミノサイクリン、サラゾスルファピリジン、シプロフロキサシン、ガチフロキサシン、ノルフロキサシン、アシクロビル、イトラコナゾール、テルビナフィン、フルコナゾール、ミコナゾール等が挙げられる。 Still further, antibiotics include, for example, clindamycin, lincomycin, vancomycin, kanamycin, amoxicillin, ampicillin, cefaclor, cephalexin, cefixime, cefpodoxime, cefdinir, cefteram, cefpodoxime, fosfomycin, faropenem, erythromycin, azithromycin, clarithromycin , Roxithromycin, chloramphenicol, tetracycline, minocycline, salazosulfapyridine, ciprofloxacin, gatifloxacin, norfloxacin, acyclovir, itraconazole, terbinafine, fluconazole, miconazole and the like.
本発明の口腔内崩壊錠には、上記成分以外にも本発明の効果を損なわない範囲で、適宜、従来公知の任意成分、例えば、種々の滑沢剤、可溶化剤、緩衝剤、吸着剤、懸濁化剤、抗酸化剤、充填剤、pH調整剤、賦形剤、分散剤、崩壊剤、崩壊補助剤、防湿剤、防腐剤、溶剤、溶解補助剤、流動化剤等を使用することができる。 In the orally disintegrating tablet of the present invention, conventionally known optional components such as various lubricants, solubilizers, buffers, adsorbents, etc., as long as the effects of the present invention other than the above components are not impaired. , Suspending agents, antioxidants, fillers, pH adjusting agents, excipients, dispersants, disintegrating agents, disintegrating aids, moisture-proofing agents, preservatives, solvents, solubilizing agents, fluidizing agents, etc. be able to.
このうち賦形剤としては、例えば、乳糖、精製白糖、結晶セルロース、デキストラン、デキストリン、ブドウ糖、粉糖等が挙げられる。崩壊剤としては例えば、カルメロース、カルメロースカルシウム、クロスカルメロースナトリウム、低置換度ヒドロキシプロピルメチルセルロース、結晶セルロース、ヒドロキシプロピルスターチ等が挙げられる。 Among these, examples of the excipient include lactose, purified white sugar, crystalline cellulose, dextran, dextrin, glucose, and powdered sugar. Examples of the disintegrant include carmellose, carmellose calcium, croscarmellose sodium, low-substituted hydroxypropyl methylcellulose, crystalline cellulose, and hydroxypropyl starch.
また滑沢剤としては、例えば、ステアリン酸マグネシウム、ステアリン酸カルシウム、ステアリン酸、タルク、ショ糖脂肪酸エステル等が挙げられる。また、コーティング剤としては、例えば、ヒドロキシプロピルメチルセルロース、アクリル酸エチル・メタクリル酸メチルコポリマー、アミノアルキルメタクリレートコポリマーE、アミノアルキルメタクリレートコポリマーRS、ヒドロキシプロピルメチルセルロースフタレート、メタクリル酸コポリマーL、メタクリル酸コポリマーLD、メタクリル酸コポリマーS等が挙げられる。更に、矯味成分としては、例えば、クエン酸、酒石酸、リンゴ酸等が挙げられる。発泡剤としては、例えば、重曹等が挙げられる。人工甘味料としては、例えば、サッカリンナトリウム、グリチルリチン二カリウム、アスパルテーム、ステビア、ソーマチン等が挙げられる。マスキング剤としては、例えば、エチルセルロース等の水不溶性高分子、メタアクリル酸メチル・メタアクリル酸ブチル・メタアクリル酸ジエチルアミノエチル・コポリマー等の胃溶性高分子などが挙げられる。 Examples of the lubricant include magnesium stearate, calcium stearate, stearic acid, talc, and sucrose fatty acid ester. Examples of the coating agent include hydroxypropyl methylcellulose, ethyl acrylate / methyl methacrylate copolymer, aminoalkyl methacrylate copolymer E, aminoalkyl methacrylate copolymer RS, hydroxypropyl methylcellulose phthalate, methacrylic acid copolymer L, methacrylic acid copolymer LD, methacrylic acid Acid copolymer S etc. are mentioned. Furthermore, examples of the taste masking component include citric acid, tartaric acid, malic acid and the like. Examples of the foaming agent include sodium bicarbonate. Examples of the artificial sweetener include saccharin sodium, dipotassium glycyrrhizin, aspartame, stevia, thaumatin and the like. Examples of the masking agent include water-insoluble polymers such as ethyl cellulose and gastric polymers such as methyl methacrylate / butyl methacrylate / diethylaminoethyl methacrylate copolymer.
以上説明した本発明の圧縮成型製剤は、生産、輸送の際の十分な硬度と、口腔内での迅速な崩壊を両立したものである。また、例えば、1時間当たり5万錠ないし20万錠という高速打錠においても打錠障害がなく、摩損度も低いものであるため、高い生産性が期待できる。 The compression-molded preparation of the present invention described above is compatible with sufficient hardness during production and transportation and rapid disintegration in the oral cavity. In addition, for example, even in high-speed tableting of 50,000 to 200,000 tablets per hour, since there is no tableting trouble and the friability is low, high productivity can be expected.
以下に実施例を挙げ、本発明を更に詳しく説明するが、本発明はこれらの実施例に何ら制約されるものではない。 EXAMPLES The present invention will be described in more detail with reference to examples below, but the present invention is not limited to these examples.
実 施 例 1
口腔内崩壊錠:
下記表1の処方および製法で口腔内崩壊錠を製造した。Example 1
Orally disintegrating tablets:
Orally disintegrating tablets were produced according to the formulation and production method shown in Table 1 below.
< 処方 >
< 製 法 >
ポリビニルアルコールとアルファー化デンプンを水で溶解させ、水溶液を調製した。この水溶液を用い、D−マンニトールとデルタ型マンニトールの混合物を流動層にて造粒した。この造粒物にクロスポビドン、アスパルテームおよびステアリン酸マグネシウムを添加して圧縮成型し、1錠当たり180mgの口腔内崩壊錠を得た。なお、圧縮成型には、畑製作所のHT−X45MS−UW型中型打錠機(ターンテーブルの半径:23cm、杵の本数:45本)を使用し、打錠圧を800kgf、ターンテーブルの回転数を20回〜60回/分に変化させて口腔内崩壊錠(「錠剤1」とする)を製造した。なお、錠剤2ないし4は、ポリビニルアルコールに代えてポリビニルアルコール−ポリエチレングリコールグラフトコポリマー(錠剤2)、コポリビドン(錠剤3)、ポリビニルアルコール−アクリルコポリマー(錠剤4)をそれぞれ用いる以外は、上記製法と同様にして調製した。<Production method>
Polyvinyl alcohol and pregelatinized starch were dissolved in water to prepare an aqueous solution. Using this aqueous solution, a mixture of D-mannitol and delta mannitol was granulated in a fluidized bed. Crospovidone, aspartame and magnesium stearate were added to this granulated product and compression molded to obtain 180 mg orally disintegrating tablets per tablet. For compression molding, Hata Seisakusho's HT-X45MS-UW medium size tablet press (turntable radius: 23 cm, number of punches: 45), tableting pressure of 800 kgf, turntable rotation speed Was changed from 20 times to 60 times / min to produce an orally disintegrating tablet (referred to as “Tablet 1”). Tablets 2 to 4 are the same as in the above production method except that polyvinyl alcohol-polyethylene glycol graft copolymer (tablet 2), copolyvidone (tablet 3), and polyvinyl alcohol-acrylic copolymer (tablet 4) are used instead of polyvinyl alcohol. It was prepared as follows.
実 施 例 2
口腔内崩壊錠の評価(1):
実施例1で調製した口腔内崩壊錠について、得られた錠剤1〜4の硬度、摩損度、口腔内での崩壊時間および打錠障害の有無を評価した。この結果を表2に示す。Example 2
Evaluation of orally disintegrating tablets (1):
About the orally disintegrating tablet prepared in Example 1, the hardness of the obtained tablets 1-4, a friability, the disintegration time in an oral cavity, and the presence or absence of tableting trouble were evaluated. The results are shown in Table 2.
< 評価方法 >
各項目の評価は、下記の通り行った。
硬 度: 硬度計(錠剤破壊強度測定器TH−303MP:富山産業(株))を使用して錠剤の硬度を測定した。
摩損度: 摩損度試験機(錠剤摩損度試験機:ミナトメディカル(株))を使用して錠剤の摩損の状況を確認した(試験時間30分、錠剤数量100錠)
口腔内崩壊時間: 成人男性をパネラーとし、製造した錠剤を口に含み、錠剤が崩壊するまでの時間を測定した。
打錠障害の有無: 打錠中にキャッピング、ラミネーション、スティッキング、ダイフリクション、杵付着等の打錠障害の有無について評価した。<Evaluation method>
Each item was evaluated as follows.
Hardness: The hardness of the tablets was measured using a hardness meter (Tablet Strength Tester TH-303MP: Toyama Sangyo Co., Ltd.).
Abrasion degree: A friability tester (tablet friability tester: Minato Medical Co., Ltd.) was used to confirm the state of tablet abrasion (test time 30 minutes, tablet quantity 100 tablets).
Oral disintegration time: An adult male was used as a panel, the manufactured tablet was included in the mouth, and the time until the tablet disintegrated was measured.
Presence or absence of tableting failure: The presence or absence of tableting failure such as capping, lamination, sticking, die friction and wrinkle adhesion during tableting was evaluated.
< 結 果 >
この結果、回転数が20から60回/分の間で、硬度、摩損度が優れ、打錠障害のない口腔内崩壊錠が得られ、本発明の処方により、時間当たり50,000錠以上の高速打錠が可能であることが明らかになった。 As a result, an orally disintegrating tablet with excellent hardness and friability and no tableting trouble was obtained at a rotational speed of 20 to 60 times / minute. According to the formulation of the present invention, 50,000 tablets or more per hour were obtained. It became clear that high-speed tableting is possible.
実 施 例 3
口腔内崩壊錠の評価(2):
実施例1の錠剤1において、ターンテーブルの回転数を40回/分とし、打錠圧を変える以外は同様にして口腔内崩壊錠を調製し、得られた錠剤の硬度、摩損度、口腔内での崩壊時間および打錠障害の有無を実施例2と同様に評価した。この結果を表3に示す。Example 3
Evaluation of orally disintegrating tablets (2):
In tablet 1 of Example 1, an orally disintegrating tablet was prepared in the same manner except that the turntable rotation speed was 40 times / minute and the tableting pressure was changed. The hardness, friability, The disintegration time and the presence or absence of tableting failure were evaluated in the same manner as in Example 2. The results are shown in Table 3.
< 結 果 >
この結果から、回転数が40回/分という高速回転であっても、硬度、摩損度が優れ、打錠障害のない口腔内速崩錠が得られることが明らかになり、その条件下で打錠圧を変化させることにより、硬度や、口腔内崩壊時間の異なる口腔内崩壊錠が得られることが明らかになった。 From this result, it is clear that even in the case of high speed rotation of 40 rotations / minute, it is possible to obtain an intraoral rapidly disintegrating tablet having excellent hardness and friability and no tableting trouble. It was revealed that orally disintegrating tablets with different hardness and disintegrating time in the oral cavity can be obtained by changing the tablet pressure.
本発明の圧縮成型製剤は、口腔内での速やかな崩壊性と生産、輸送等に必要な硬度を兼ね備えるものであり、種々の生理活性物質を経口投与する場合に有利に使用することができるものである。 The compression-molded preparation of the present invention combines the rapid disintegration property in the oral cavity with the hardness necessary for production, transportation, etc., and can be advantageously used when orally administering various physiologically active substances. It is.
また、本発明の圧縮成型製剤の製造方法によれば、外部滑択装置なしで、杵付着、キャッピング、ダイフリクション等の打錠障害を起こさずに安定して打錠することができ、圧縮成型時間を短縮しても速やかな崩壊性を有する圧縮成型製剤を得ることができる。また、高速で圧縮成型を行うことが可能であるため、生産性が飛躍的に向上する。 Further, according to the method for producing a compression-molded preparation of the present invention, it is possible to stably perform tableting without causing tableting troubles such as wrinkle adhesion, capping and die friction without using an external sliding device. Even if the time is shortened, a compression-molded preparation having rapid disintegration can be obtained. Further, since the compression molding can be performed at a high speed, the productivity is dramatically improved.
従って、本発明方法は、圧縮成型製剤の製造方法として極めて有利なものである。 Therefore, the method of the present invention is extremely advantageous as a method for producing a compression-molded preparation.
Claims (11)
The method for producing a compression-molded preparation according to any one of claims 8 to 10 , wherein the number of tableting per hour is 50,000 or more.
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US20120121703A1 (en) * | 2010-07-20 | 2012-05-17 | Japan Tobacco Inc. | Tablet containing ferric citrate |
PL3093011T3 (en) * | 2010-12-17 | 2021-09-06 | Merck Patent Gmbh | Method for the preparation of directly tablettable mannitol |
JP6245786B2 (en) * | 2011-10-17 | 2017-12-13 | 大同化成工業株式会社 | Pharmaceutical binding agent and preparation using the binding agent |
JP6204141B2 (en) * | 2013-04-22 | 2017-09-27 | テイカ製薬株式会社 | Oral rapidly disintegrating composition for solid preparation |
JP2015063521A (en) * | 2013-09-02 | 2015-04-09 | 科研製薬株式会社 | Tablet with high drug content and production method thereof |
JP6188183B1 (en) * | 2016-05-23 | 2017-08-30 | 大原薬品工業株式会社 | Method for stable production of high-drug compressed tablets |
CN106236717A (en) * | 2016-08-30 | 2016-12-21 | 佛山市弘泰药物研发有限公司 | A kind of Zaltoprofen oral cavity disintegration tablet and preparation method thereof |
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Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH02502720A (en) * | 1987-03-25 | 1990-08-30 | イー・アイ・デユポン・デ・ニモアス・アンド・カンパニー | Use of vinyl alcohol homopolymers and copolymers to tablet active substances |
WO2000048575A1 (en) * | 1999-02-17 | 2000-08-24 | Kyowa Hakko Kogyo Co., Ltd. | Tablets and process for producing tablets |
JP2000516263A (en) * | 1997-12-29 | 2000-12-05 | ザ、プロクター、エンド、ギャンブル、カンパニー | Tablet composition |
JP2005306778A (en) * | 2004-04-21 | 2005-11-04 | Basf Ag | Sustained-release formulation and method for producing the same |
WO2006106923A1 (en) * | 2005-03-31 | 2006-10-12 | Taiyo Yakuhin Co., Ltd. | Disintegrating tablet in oral cavity and process for producing the same |
WO2006126681A1 (en) * | 2005-05-26 | 2006-11-30 | Dainippon Sumitomo Pharma Co., Ltd. | Pharmaceutical composition |
JP2007191474A (en) * | 2005-12-20 | 2007-08-02 | Takeda Chem Ind Ltd | Colored sugar-coated tablet |
WO2007128724A1 (en) * | 2006-05-04 | 2007-11-15 | Boehringer Ingelheim International Gmbh | Dpp iv inhibitor formulations |
WO2008078727A1 (en) * | 2006-12-26 | 2008-07-03 | Daiichi Sankyo Company, Limited | Pharmaceutical composition having improved dissolution property |
-
2009
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- 2009-09-28 JP JP2010531841A patent/JP5694773B2/en active Active
- 2009-09-29 TW TW98132964A patent/TW201023850A/en unknown
Patent Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH02502720A (en) * | 1987-03-25 | 1990-08-30 | イー・アイ・デユポン・デ・ニモアス・アンド・カンパニー | Use of vinyl alcohol homopolymers and copolymers to tablet active substances |
JP2000516263A (en) * | 1997-12-29 | 2000-12-05 | ザ、プロクター、エンド、ギャンブル、カンパニー | Tablet composition |
WO2000048575A1 (en) * | 1999-02-17 | 2000-08-24 | Kyowa Hakko Kogyo Co., Ltd. | Tablets and process for producing tablets |
JP2005306778A (en) * | 2004-04-21 | 2005-11-04 | Basf Ag | Sustained-release formulation and method for producing the same |
WO2006106923A1 (en) * | 2005-03-31 | 2006-10-12 | Taiyo Yakuhin Co., Ltd. | Disintegrating tablet in oral cavity and process for producing the same |
WO2006126681A1 (en) * | 2005-05-26 | 2006-11-30 | Dainippon Sumitomo Pharma Co., Ltd. | Pharmaceutical composition |
JP2007191474A (en) * | 2005-12-20 | 2007-08-02 | Takeda Chem Ind Ltd | Colored sugar-coated tablet |
WO2007128724A1 (en) * | 2006-05-04 | 2007-11-15 | Boehringer Ingelheim International Gmbh | Dpp iv inhibitor formulations |
JP2009535376A (en) * | 2006-05-04 | 2009-10-01 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | DPPIV inhibitor preparation |
WO2008078727A1 (en) * | 2006-12-26 | 2008-07-03 | Daiichi Sankyo Company, Limited | Pharmaceutical composition having improved dissolution property |
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