JP2016222648A - Solid preparation - Google Patents
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- JP2016222648A JP2016222648A JP2016096114A JP2016096114A JP2016222648A JP 2016222648 A JP2016222648 A JP 2016222648A JP 2016096114 A JP2016096114 A JP 2016096114A JP 2016096114 A JP2016096114 A JP 2016096114A JP 2016222648 A JP2016222648 A JP 2016222648A
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- 238000002360 preparation method Methods 0.000 title claims abstract description 47
- 239000007787 solid Substances 0.000 title claims abstract description 32
- HSRJKNPTNIJEKV-UHFFFAOYSA-N Guaifenesin Chemical compound COC1=CC=CC=C1OCC(O)CO HSRJKNPTNIJEKV-UHFFFAOYSA-N 0.000 claims abstract description 47
- 229960002146 guaifenesin Drugs 0.000 claims abstract description 44
- 238000004519 manufacturing process Methods 0.000 claims abstract description 13
- WMGSQTMJHBYJMQ-UHFFFAOYSA-N aluminum;magnesium;silicate Chemical compound [Mg+2].[Al+3].[O-][Si]([O-])([O-])[O-] WMGSQTMJHBYJMQ-UHFFFAOYSA-N 0.000 claims description 19
- 229940079832 sodium starch glycolate Drugs 0.000 claims description 18
- 239000008109 sodium starch glycolate Substances 0.000 claims description 18
- 229920003109 sodium starch glycolate Polymers 0.000 claims description 18
- 239000008187 granular material Substances 0.000 abstract description 19
- 238000000034 method Methods 0.000 abstract description 11
- 239000011248 coating agent Substances 0.000 abstract description 2
- 238000000576 coating method Methods 0.000 abstract description 2
- 229920002472 Starch Polymers 0.000 abstract 1
- JAUGGEIKQIHSMF-UHFFFAOYSA-N dialuminum;dimagnesium;dioxido(oxo)silane;oxygen(2-);hydrate Chemical compound O.[O-2].[O-2].[Mg+2].[Mg+2].[Al+3].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O.[O-][Si]([O-])=O JAUGGEIKQIHSMF-UHFFFAOYSA-N 0.000 abstract 1
- 230000004927 fusion Effects 0.000 abstract 1
- 229940023144 sodium glycolate Drugs 0.000 abstract 1
- 235000019698 starch Nutrition 0.000 abstract 1
- 239000008107 starch Substances 0.000 abstract 1
- JEJAMASKDTUEBZ-UHFFFAOYSA-N tris(1,1,3-tribromo-2,2-dimethylpropyl) phosphate Chemical compound BrCC(C)(C)C(Br)(Br)OP(=O)(OC(Br)(Br)C(C)(C)CBr)OC(Br)(Br)C(C)(C)CBr JEJAMASKDTUEBZ-UHFFFAOYSA-N 0.000 abstract 1
- 239000003826 tablet Substances 0.000 description 12
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
- 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 8
- 238000005469 granulation Methods 0.000 description 8
- 230000003179 granulation Effects 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- 238000005550 wet granulation Methods 0.000 description 7
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 6
- 229960001948 caffeine Drugs 0.000 description 6
- 229920002678 cellulose Polymers 0.000 description 6
- 239000001913 cellulose Substances 0.000 description 6
- 239000003205 fragrance Substances 0.000 description 6
- RYYVLZVUVIJVGH-UHFFFAOYSA-N trimethylxanthine Natural products CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 5
- 235000019359 magnesium stearate Nutrition 0.000 description 5
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 description 4
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 4
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 4
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 229960002477 riboflavin Drugs 0.000 description 4
- 235000019192 riboflavin Nutrition 0.000 description 4
- 239000002151 riboflavin Substances 0.000 description 4
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 4
- 235000012239 silicon dioxide Nutrition 0.000 description 4
- DBAKFASWICGISY-BTJKTKAUSA-N Chlorpheniramine maleate Chemical compound OC(=O)\C=C/C(O)=O.C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 DBAKFASWICGISY-BTJKTKAUSA-N 0.000 description 3
- NTCYWJCEOILKNG-ROLPUNSJSA-N [(1r,2s)-1-hydroxy-1-phenylpropan-2-yl]-dimethylazanium;chloride Chemical compound Cl.CN(C)[C@@H](C)[C@H](O)C1=CC=CC=C1 NTCYWJCEOILKNG-ROLPUNSJSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 229940046978 chlorpheniramine maleate Drugs 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- -1 magnesium metasilicate magnesium aluminate Chemical class 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 229960005489 paracetamol Drugs 0.000 description 3
- WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.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](O)[C@H]1O WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000000954 anitussive effect Effects 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 238000013329 compounding Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 229940073563 dl- methylephedrine hydrochloride Drugs 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000003419 expectorant effect Effects 0.000 description 2
- 239000000820 nonprescription drug Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 1
- 206010021118 Hypotonia Diseases 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical group C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 206010036790 Productive cough Diseases 0.000 description 1
- 150000004645 aluminates Chemical class 0.000 description 1
- 239000002269 analeptic agent Substances 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 239000003434 antitussive agent Substances 0.000 description 1
- 229940124584 antitussives Drugs 0.000 description 1
- 229940124630 bronchodilator Drugs 0.000 description 1
- 239000000168 bronchodilator agent Substances 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229960000456 carbinoxamine maleate Drugs 0.000 description 1
- GVNWHCVWDRNXAZ-BTJKTKAUSA-N carbinoxamine maleate Chemical compound OC(=O)\C=C/C(O)=O.C=1C=CC=NC=1C(OCCN(C)C)C1=CC=C(Cl)C=C1 GVNWHCVWDRNXAZ-BTJKTKAUSA-N 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 229960000920 dihydrocodeine Drugs 0.000 description 1
- RBOXVHNMENFORY-DNJOTXNNSA-N dihydrocodeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC RBOXVHNMENFORY-DNJOTXNNSA-N 0.000 description 1
- 238000002845 discoloration Methods 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000007908 dry granulation Methods 0.000 description 1
- 239000003172 expectorant agent Substances 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 239000007941 film coated tablet Substances 0.000 description 1
- 239000007888 film coating Substances 0.000 description 1
- 238000009501 film coating Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000002267 hypothalamic effect Effects 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 229940051020 methylephedrine hydrochloride Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000036640 muscle relaxation Effects 0.000 description 1
- 201000009240 nasopharyngitis Diseases 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 238000005096 rolling process Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 208000024794 sputum Diseases 0.000 description 1
- 210000003802 sputum Anatomy 0.000 description 1
- 229940071117 starch glycolate Drugs 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000000859 sublimation Methods 0.000 description 1
- 230000008022 sublimation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
Abstract
Description
本発明は、グアイフェネシンを含有する内服用固形製剤に関する。 The present invention relates to a solid preparation for internal use containing guaifenesin.
一般用医薬品（ＯＴＣ）分野の薬剤開発においては、如何に効果的にかぜの諸症状を除去等するかが重要である。かぜ症候群のうち、特に痰の喀出（去痰）を図ることは、患者の負担が軽減されるため大変重要である。
グアイフェネシン（Guaifenesin：３−（２−メトキシフェノキシ）−１，２−プロパンジオール）は、視床下部の抑制及び気管支筋の弛緩による鎮咳作用と、気道分泌液の増加による去痰作用を有し、優れた去痰作用を有する化合物として広く知られている薬物である。一方で、グアイフェネシンは融点が約８１℃であり、製剤化時に製造機器機で発生する摩擦や熱により溶融し、機器への付着が生じ、機器の停止や付着物の混入による質量ばらつきなどの製造性の著しい低下といった問題が生じる。
グアイフェネシン含有製剤としては、グアイフェネシンの変色防止に関する技術（特許文献１）や昇華を抑制する技術（特許文献２）などが知られているが、グアイフェネシンの製造機器への付着については何ら記載も示唆もない。
In drug development in the field of over-the-counter medicines (OTC), it is important how to effectively eliminate cold symptoms. Among cold syndromes, it is very important to eliminate sputum, especially because it reduces the burden on the patient.
Guaifenesin (3- (2-methoxyphenoxy) -1,2-propanediol) has an antitussive effect due to hypothalamic inhibition and bronchial muscle relaxation, and an expectorant effect due to increased airway secretion. It is a drug widely known as a compound having expectorant action. On the other hand, guaifenesin has a melting point of about 81 ° C., and melts due to friction and heat generated in the manufacturing equipment machine during formulation, causing adhesion to the equipment, production of mass variation due to equipment stoppage and contamination Problems such as a significant decrease in sex occur.
As a guaifenesin-containing preparation, there are known a technique for preventing discoloration of guaifenesin (Patent Document 1) and a technique for suppressing sublimation (Patent Document 2). However, there is no description or suggestion about the adhesion of guaifenesin to manufacturing equipment. Absent.
本発明は、グアイフェネシンを配合しても、摩擦や溶融による製造機器への付着がなく、安定生産可能なグアイフェネシン含有製剤を提供することにある。 An object of the present invention is to provide a guaifenesin-containing preparation that can be stably produced even when guaifenesin is blended, without being attached to production equipment due to friction or melting.
そこで、本発明者らが鋭意検討した結果、上記目的を達成するためにグアイフェネシンに、メタケイ酸アルミン酸マグネシウムとデンプングリコール酸ナトリウムを配合すると、上記課題が解決されることを見出し、本発明を完成した。 Therefore, as a result of intensive studies by the present inventors, it has been found that the above-mentioned problems can be solved by adding magnesium aluminate metasilicate and sodium starch glycolate to guaifenesin in order to achieve the above object, and the present invention has been completed. did.
すなわち、本発明は
（１）グアイフェネシン、メタケイ酸アルミン酸マグネシウム、及びデンプングリコール酸ナトリウムを含有することを特徴とする内服用固形製剤、
（２）グアイフェネシン含有造粒物、メタケイ酸アルミン酸マグネシウム、及びデンプングリコール酸ナトリウムを含有することを特徴とする内服用固形製剤、
（３）グアイフェネシン含有造粒物中にメタケイ酸アルミン酸マグネシウムを含む、（２）に記載の内服用固形製剤。
（４）グアイフェネシン含有造粒物中に、さらにデンプングリコール酸ナトリウムを含む、（３）に記載の内服用固形製剤。
（５）グアイフェネシンの含有量が、製剤全体に対し、１〜３０質量％である（１）〜（４）のいずれかに記載の内服用固形製剤、
（６）デンプングリコール酸ナトリウムの含有量が、グアイフェネシン１質量部に対して０．１〜０．７質量部である（１）又は（２）に記載の内服用固形製剤、
（７）メタケイ酸アルミン酸マグネシウムの含有量が、グアイフェネシン１質量部に対して０．１〜０．５質量部である（１）又は（２）に記載の内服用固形製剤、
（８）グアイフェネシン及びメタケイ酸アルミン酸マグネシウムを含有する造粒物に、デンプングリコール酸ナトリウムを混合することを特徴とする（１）〜（７）のいずれかに記載の内服用固形製剤の製造方法、
である。
That is, the present invention includes (1) a solid preparation for internal use, characterized by containing guaifenesin, magnesium aluminate metasilicate, and sodium starch glycolate,
(2) a solid preparation for internal use, characterized by containing a granule containing guaifenesin, magnesium aluminate metasilicate, and sodium starch glycolate;
(3) The solid preparation for internal use according to (2), wherein the guaifenesin-containing granulated product contains magnesium aluminate metasilicate.
(4) The solid preparation for internal use according to (3), further comprising sodium starch glycolate in the guaifenesin-containing granulated product.
(5) The solid preparation for internal use according to any one of (1) to (4), wherein the content of guaifenesin is 1 to 30% by mass relative to the whole preparation,
(6) The solid preparation for internal use according to (1) or (2), wherein the content of sodium starch glycolate is 0.1 to 0.7 parts by mass relative to 1 part by mass of guaifenesin,
(7) The solid preparation for internal use according to (1) or (2), wherein the content of magnesium aluminate metasilicate is 0.1 to 0.5 parts by mass with respect to 1 part by mass of guaifenesin.
(8) The method for producing a solid preparation for internal use according to any one of (1) to (7), wherein sodium granule glycolate is mixed with a granulated product containing guaifenesin and magnesium aluminate metasilicate. ,
It is.
本発明により、グアイフェネシン配合製剤の生産性を向上し、製品価値の高い内服用固形製剤が得られる。 本発明の内服用固形製剤は、顆粒コーティング操作等の煩雑な製造工程を必要とせず、グアイフェネシンの熱安定性を備えた内服用固形製剤を簡便な方法で製造することができる。 According to the present invention, the productivity of a guaifenesin combination preparation is improved, and a solid preparation for internal use having a high product value can be obtained. The solid preparation for internal use of the present invention does not require complicated production steps such as granule coating operation, and can produce a solid preparation for internal use having the thermal stability of guaifenesin by a simple method.
本発明の内服用固形製剤中におけるグアイフェネシンの含有量は、その薬効を示す量であれば特に限定されるものではないが、通常０．５〜５０質量％、好ましくは１〜３０質量％である。 The content of guaifenesin in the solid preparation for internal use of the present invention is not particularly limited as long as it shows the medicinal effect, but is usually 0.5 to 50% by mass, preferably 1 to 30% by mass. .
本発明の内服用固形製剤中におけるメタケイ酸アルミン酸マグネシウムの含有量は、特に限定されるものではないが、通常０．１〜２０質量％、好ましくは０．５〜５．０質量％が好ましい。また、グアイフェネシンとメタケイ酸アルミン酸マグネシウムの配合比（質量比）は、１：０．０５〜１．０、特に１：０．１〜０．５が好ましい。 The content of magnesium metasilicate magnesium aluminate in the solid preparation for internal use of the present invention is not particularly limited, but is usually 0.1 to 20% by mass, preferably 0.5 to 5.0% by mass. . Moreover, the compounding ratio (mass ratio) of guaifenesin and magnesium aluminate metasilicate is preferably 1: 0.05 to 1.0, particularly preferably 1: 0.1 to 0.5.
本発明の内服用固形製剤中におけるデンプングリコール酸ナトリウムの含有量は、特に限定されるものではないが、通常０．５〜２０質量％、好ましくは１．０〜１０質量％である。また、また、グアイフェネシンとデンプングリコール酸ナトリウムの配合比（質量比）は、１：０．０５〜１．０、特に１：０．１〜０．７が好ましい。 The content of sodium starch glycolate in the solid preparation for internal use of the present invention is not particularly limited, but is usually 0.5 to 20% by mass, preferably 1.0 to 10% by mass. Moreover, the compounding ratio (mass ratio) of guaifenesin and sodium starch glycolate is preferably 1: 0.05 to 1.0, particularly preferably 1: 0.1 to 0.7.
また、本発明の内服用固形製剤中にはグアイフェネシンの他に、本発明の効果を損なわない質的、量的範囲で、通常用いられる他の有効成分（例えばアセトアミノフェン、イブプロフェン等の解熱鎮痛剤、ジヒドロコデインリン酸塩等の鎮咳剤、クロルフェニラミンマレイン酸塩、カルビノキサミンマレイン酸塩等の抗ヒスタミン剤、メチルエフェドリン塩酸塩等の気管支拡張剤、カフェイン無水物等の中枢興奮剤など）、賦形剤、崩壊剤、結合剤などを配合しうる。 Further, in the solid preparation for internal use of the present invention, in addition to guaifenesin, other active ingredients usually used (for example, antipyretic analgesia such as acetaminophen, ibuprofen, etc.) within a qualitative and quantitative range that does not impair the effects of the present invention. Drugs, antitussives such as dihydrocodeine phosphate, antihistamines such as chlorpheniramine maleate and carbinoxamine maleate, bronchodilators such as methylephedrine hydrochloride, and central stimulants such as caffeine anhydride) Forming agents, disintegrating agents, binders and the like can be incorporated.
本発明の内服用固形製剤の剤形は、特に限定されず、散剤、細粒剤、顆粒剤、丸剤、錠剤（フィルムコーティング錠、糖衣錠、積層錠を含む）、カプセル剤等の剤形を包含するが、好ましくは錠剤である。それぞれ必要に応じて有効成分、賦形剤、結合剤、崩壊剤、フィルムコーティング剤、滑沢剤、抗酸化剤、香料、および着色剤等の慣用の製剤添加剤を適当量配合しても良い。 The dosage form of the solid preparation for internal use of the present invention is not particularly limited, and dosage forms such as powders, fine granules, granules, pills, tablets (including film-coated tablets, sugar-coated tablets, laminated tablets), capsules, etc. Preferably, it is a tablet. If necessary, an appropriate amount of conventional formulation additives such as active ingredients, excipients, binders, disintegrants, film coating agents, lubricants, antioxidants, fragrances, and coloring agents may be blended. .
本発明の内服用固形製剤は、常法により製造することができ、その方法は特に限定されるものではないが、本発明のグアイフェネシンは造粒されていることが好ましい。造粒方法は特に限定されず、その剤形に応じて、任意の慣用の方法例えば攪拌造粒、流動層造粒、押し出し造粒、転動流動造粒、乾式造粒などの方法により造粒して製造する。 The solid preparation for internal use of the present invention can be produced by a conventional method, and the method is not particularly limited, but the guaifenesin of the present invention is preferably granulated. The granulation method is not particularly limited, and depending on the dosage form, granulation is performed by any conventional method such as stirring granulation, fluidized bed granulation, extrusion granulation, rolling fluid granulation, dry granulation, etc. To manufacture.
本発明のメタケイ酸アルミン酸マグネシウムは、グアイフェネシン含有造粒物中に含まれてもいいし、グアイフェネシン含有造粒物以外に含まれてもいいし、その両方に含まれてもいいが、本発明の製造機器への付着の改善効果の点から、少なくともグアイフェネシン含有造粒物中に含まれるのが好ましい。
また、本発明のデンプングリコール酸マグネシウムは、グアイフェネシン含有造粒物中に含まれてもいいし、グアイフェネシン含有造粒物以外に含まれてもいいし、その両方に含まれていてもよい。
上記のように造粒した後、造粒物を被覆しても良い。また、その造粒物に適宜上記有効成分や賦形剤などの慣用の製剤添加剤を配合してもよく、また、このようにして得た混合物を打錠すれば錠剤を得ることができる。造粒物を用いて市販の積層錠剤機により２層以上の多層錠の錠剤としてもよい。
The magnesium aluminate metasilicate of the present invention may be contained in the guaifenesin-containing granulated product, may be contained other than the guaifenesin-containing granulated product, or may be contained in both of them. In view of the effect of improving the adhesion to the manufacturing equipment, it is preferably contained in at least the guaifenesin-containing granulated product.
The magnesium starch glycolate of the present invention may be contained in the guaifenesin-containing granulated product, may be contained other than the guaifenesin-containing granulated product, or may be contained in both of them.
After granulation as described above, the granulated product may be coated. Further, conventional granule additives such as the above active ingredients and excipients may be appropriately blended in the granulated product, and tablets can be obtained by tableting the mixture thus obtained. It is good also as a tablet of a multilayer tablet of two or more layers using a granulation thing with a commercially available laminated tablet machine.
以下、実施例、比較例及び試験例を挙げて、本発明を更に詳細に説明する。 Hereinafter, the present invention will be described in more detail with reference to Examples, Comparative Examples, and Test Examples.
（実施例１）
製剤全体に対し、グアイフェネシン７．１質量％、リボフラビン０．１質量％、結晶セルロース１０．９質量％、ヒドロキシプロピルセルロース１．１質量％、デンプングリコール酸ナトリウム０．８質量％、軽質無水ケイ酸０．３質量％、メタケイ酸アルミン酸マグネシウム１．１質量％になるように秤量した粉体を、湿式造粒法により造粒した。また、製剤全体に対してアセトアミノフェン３５．６質量％、ｄｌ−メチルエフェドリン塩酸塩２．４質量％、クロルフェニラミンマレイン酸塩０．３質量％、リボフラビン０．４質量％、結晶セルロース２１．９質量％、ヒドロキシプロピルセルロース２．４質量％、乳糖水和物７．８質量％、軽質無水ケイ酸１．７質量％、デンプングリコール酸ナトリウム質量１．１％になるように秤量した粉体を、湿式造粒法により造粒した。以上より得られた顆粒と、製剤全体に対し、メタケイ酸アルミン酸マグネシウムを１．５質量％、無水カフェイン３．０質量％、ステアリン酸マグネシウム０．５質量％、香料０．１質量％になるように秤量した粉体とを混合し、打錠用顆粒を得た。
Example 1
Guaiphenesin 7.1% by mass, riboflavin 0.1% by mass, crystalline cellulose 10.9% by mass, hydroxypropylcellulose 1.1% by mass, sodium starch glycolate 0.8% by mass, light anhydrous silicic acid, based on the whole preparation The powder weighed so as to be 0.3% by mass and 1.1% by mass of magnesium aluminate metasilicate was granulated by a wet granulation method. In addition, 35.6% by mass of acetaminophen, 2.4% by mass of dl-methylephedrine hydrochloride, 0.3% by mass of chlorpheniramine maleate, 0.4% by mass of riboflavin, crystalline cellulose 21 with respect to the whole preparation 0.9% by weight, hydroxypropylcellulose 2.4% by weight, lactose hydrate 7.8% by weight, light anhydrous silicic acid 1.7% by weight, sodium starch glycolate weight 1.1% The body was granulated by wet granulation. From the above-obtained granules and the whole preparation, magnesium aluminate metasilicate was added to 1.5% by mass, anhydrous caffeine 3.0% by mass, magnesium stearate 0.5% by mass, and fragrance 0.1% by mass. The powder thus weighed was mixed with each other to obtain granules for tableting.
（実施例２）
製剤全体に対し、グアイフェネシン７．０質量％、リボフラビン０．１質量％、結晶セルロース１２．６質量％、ヒドロキシプロピルセルロース１．９質量％、軽質無水ケイ酸０．４質量％、メタケイ酸アルミン酸マグネシウム１．２質量％になるように秤量した粉体を、湿式造粒法により造粒した。また、製剤全体に対してアセトアミノフェン３５．０質量％、ｄｌ−メチルエフェドリン塩酸塩２．３質量％、クロルフェニラミンマレイン酸塩０．３質量％、リボフラビン０．４質量％、結晶セルロース１１．８質量％、ヒドロキシプロピルセルロース３．９質量％、乳糖水和物１２．３質量％、軽質無水ケイ酸１．６質量％、デンプングリコール酸ナトリウム質量３．５％になるように秤量した粉体を、湿式造粒法により造粒した。以上より得られた顆粒と、製剤全体に対し、メタケイ酸アルミン酸マグネシウムを１．１質量％、無水カフェイン２．９質量％、ステアリン酸マグネシウム０．６質量％、硬化油０．９質量％、香料０．１質量％になるように秤量した粉体とを混合し、打錠用顆粒を得た。
(Example 2)
Guayphenesin 7.0% by mass, riboflavin 0.1% by mass, crystalline cellulose 12.6% by mass, hydroxypropylcellulose 1.9% by mass, light anhydrous silicic acid 0.4% by mass, metasilicate aluminate The powder weighed so as to be 1.2% by mass of magnesium was granulated by a wet granulation method. Further, 35.0% by mass of acetaminophen, 2.3% by mass of dl-methylephedrine hydrochloride, 0.3% by mass of chlorpheniramine maleate, 0.4% by mass of riboflavin, crystalline cellulose 11 with respect to the whole preparation 8% by mass, hydroxypropylcellulose 3.9% by mass, lactose hydrate 12.3% by mass, light anhydrous silicic acid 1.6% by mass, sodium starch glycolate mass 3.5% The body was granulated by wet granulation. From the above-obtained granules and the whole preparation, magnesium metasilicate aluminate was 1.1% by mass, anhydrous caffeine 2.9% by mass, magnesium stearate 0.6% by mass, and hardened oil 0.9% by mass. Then, powders weighed so that the fragrance was 0.1% by mass were mixed to obtain tablets for tableting.
（比較例１）
実施例１のデンプングリコール酸ナトリウムを低置換度ヒドロキシプロピルセルロースに置き換えて湿式造粒法により造粒し、得られた顆粒と、製剤全体に対し、メタケイ酸アルミン酸マグネシウムを１．５質量％、無水カフェイン３．０質量％、ステアリン酸マグネシウム０．５質量％、香料０．１質量％になるように秤量した粉体とを混合し、打錠用顆粒を得た。
(Comparative Example 1)
The sodium starch glycolate of Example 1 was replaced with low-substituted hydroxypropylcellulose and granulated by a wet granulation method, and the resulting granule and the entire preparation were 1.5% by mass of magnesium aluminate metasilicate, Powders weighed so as to be 3.0% by mass of anhydrous caffeine, 0.5% by mass of magnesium stearate, and 0.1% by mass of fragrance were mixed to obtain granules for tableting.
（比較例２）
実施例１のデンプングリコール酸ナトリウムをクロスポビドンに置き換えて湿式造粒法により造粒し、得られた顆粒と、製剤全体に対し、メタケイ酸アルミン酸マグネシウムを１．５質量％、無水カフェイン３．０質量％、ステアリン酸マグネシウム０．５質量％、香料０．１質量％になるように秤量した粉体とを混合し、打錠用顆粒を得た。
(Comparative Example 2)
The sodium starch glycolate of Example 1 was replaced with crospovidone and granulated by a wet granulation method. The obtained granules and the whole preparation were composed of 1.5% by mass of magnesium aluminate metasilicate and anhydrous caffeine 3 Powders weighed so as to be 0.0 mass%, magnesium stearate 0.5 mass%, and fragrance 0.1 mass% were mixed to obtain granules for tableting.
（比較例３）
実施例１のメタケイ酸アルミン酸マグネシウムを結晶セルロースに置き換えて湿式造粒法により造粒し、得られた顆粒と、製剤全体に対し、結晶セルロースを１．５質量％、無水カフェイン３．０質量％、ステアリン酸マグネシウム０．５質量％、香料０．１質量％になるように秤量した粉体とを混合し、打錠用顆粒を得た。
(Comparative Example 3)
The magnesium aluminate metasilicate of Example 1 was replaced with crystalline cellulose and granulated by a wet granulation method, and 1.5% by mass of crystalline cellulose and anhydrous caffeine 3.0% were obtained based on the obtained granules and the whole preparation. Powders weighed so as to be mass%, magnesium stearate 0.5 mass%, and fragrance 0.1 mass% were mixed to obtain granules for tableting.
（試験例１）
実施例１〜２、比較例１〜３の打錠用顆粒について、ロータリー式打錠機（菊水製作所製・ＶＩＲＧ ０５１９ＳＳ１ＡＺ）を用い打錠機回転数67rpmにて打錠操作を行い、行い、３分後の回転盤の付着を評価した。結果を表１に示す。
(Test Example 1)
About the granule for tableting of Examples 1-2 and Comparative Examples 1-3, tableting operation is performed by using a rotary type tableting machine (Kikusui Seisakusho, VIRG 0519SS1AZ) at a tableting machine rotation speed of 67 rpm. The adhesion of the rotating disk after minutes was evaluated. The results are shown in Table 1.
表１から明らかなように、グアイフェネシン配合製剤は、デンプングリコール酸ナトリウムを配合することで打錠機の回転盤への付着が改善することがわかった。 As is clear from Table 1, it was found that the guaifenesin formulation improved adhesion to the tablet of the tableting machine by blending sodium starch glycolate.
（実施例３）
実施例１の打錠用顆粒について、ロータリー式打錠機（菊水製作所製・ＶＩＲＧ ０５１９ＳＳ１ＡＺ）を用い打錠機回転数67rpmにて打錠操作を行い、錠剤を得た。
Example 3
The tableting granules of Example 1 were tableted using a rotary tableting machine (VIRG 0519SS1AZ, manufactured by Kikusui Seisakusho) at a tableting machine rotation speed of 67 rpm to obtain tablets.
（実施例４）
実施例２の打錠用顆粒について、ロータリー式打錠機（菊水製作所製・ＶＩＲＧ ０５１９ＳＳ１ＡＺ）を用い打錠機回転数67rpmにて打錠操作を行い、錠剤を得た。
本発明により、付着物の混入が生じない、質量バラツキのない錠剤の提供が可能となった（実施例３〜４）。
Example 4
The tableting granules of Example 2 were tableted using a rotary tableting machine (VIRG 0519SS1AZ, manufactured by Kikusui Seisakusho) at a tableting machine rotation speed of 67 rpm to obtain tablets.
According to the present invention, it has become possible to provide tablets without mass variation, in which adhering substances are not mixed (Examples 3 to 4).
本発明により、グアイフェネシンを配合しても、摩擦や溶融による製造機器への付着を顕著に抑制した内服用固形製剤を提供することが可能となる。 According to the present invention, even when guaifenesin is blended, it is possible to provide a solid preparation for internal use in which adhesion to production equipment due to friction or melting is remarkably suppressed.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH07277962A (en) * | 1994-04-05 | 1995-10-24 | Taisho Pharmaceut Co Ltd | Guaifenesin-compounded preparation |
| US20030091624A1 (en) * | 2001-09-28 | 2003-05-15 | Szymczak Christopher E. | Simethicone solid oral dosage form |
| JP2006131575A (en) * | 2004-11-08 | 2006-05-25 | Tokuyama Corp | Low-melting drug-containing granule and tablet produced by using the same |
| JP2006143650A (en) * | 2004-11-19 | 2006-06-08 | Asahi Kasei Chemicals Corp | Method for producing tablet containing medicine having high adhesiveness |
| JP2006256975A (en) * | 2005-03-15 | 2006-09-28 | Kowa Co | Guaifenesin-containing preparation |
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Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH07277962A (en) * | 1994-04-05 | 1995-10-24 | Taisho Pharmaceut Co Ltd | Guaifenesin-compounded preparation |
| US20030091624A1 (en) * | 2001-09-28 | 2003-05-15 | Szymczak Christopher E. | Simethicone solid oral dosage form |
| JP2006131575A (en) * | 2004-11-08 | 2006-05-25 | Tokuyama Corp | Low-melting drug-containing granule and tablet produced by using the same |
| JP2006143650A (en) * | 2004-11-19 | 2006-06-08 | Asahi Kasei Chemicals Corp | Method for producing tablet containing medicine having high adhesiveness |
| JP2006256975A (en) * | 2005-03-15 | 2006-09-28 | Kowa Co | Guaifenesin-containing preparation |
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